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Etoposide

Pronunciation

Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: [5R - [5α,5aβ,8aα,9β(R*)]] - 9 - [4,6 - O - ethylidene - β - d - glucopyranosyl)oxy]5,8,8a,9 - tetrahydro - 5 - (4 - hydroxy - 3,5 - dimethoxyphenyl)furo[3′,4′:6,7]naphtho[2,3 - d] - 1,3 - dioxol - 6(5aH) - one
Molecular Formula: C29H32O13
CAS Number: 33419-42-0
Brands: Etopophos, Toposar, VePesid

Warning(s)

  • Experience of Supervising Clinician
  • For administration only under the supervision of a qualified clinician experienced in the use of antineoplastic agents.c d

  • Myelosuppression
  • Severe myelosuppression with resulting infection or bleeding may occur. (See Myelosuppression under Cautions.)c d

Introduction

Antineoplastic agent; semisynthetic podophyllotoxin-derivative.1 2 3

Uses for Etoposide

Testicular Cancer

Component of various combination chemotherapeutic regimens for treatment of refractory testicular tumors in patients who have already received appropriate surgery, chemotherapy, and radiation therapy.1 256

Component of various combination chemotherapeutic regimens with cisplatin for first-line treatment of stage III or unresectable stage II nonseminomatous testicular carcinoma39 40 41 42 206 and for chemotherapy-refractory disease.2 38 39 43 44 165 182

Combination chemotherapy with etoposide, cisplatin, and bleomycin (BEP) is recommended for initial treatment of advanced nonseminomatous testicular carcinoma.198 206 207 208 209 210 211 212 213

Component of a combination chemotherapeutic regimen (ifosfamide, cisplatin, and either etoposide or vinblastine) as second-line therapy for recurrent nonseminomatous testicular carcinoma.223 241 243 244 245 246 247

Component of combination chemotherapeutic regimens (with cisplatin) for initial treatment of disseminated seminoma testis45 50 51 198 214 and treatment-refractory disease.38 43

Component of combination chemotherapeutic regimens (usually with cisplatin) for initial treatment of advanced extragonadal germ-cell tumors.52

Small Cell Lung Cancer

Component of a combination chemotherapeutic regimen with etoposide and cisplatin or carboplatin (PE) as a preferred first-line treatment of small-cell lung cancer.a 65 79 80 81 82 83 84 180 183 215 253

In combination with ifosfamide with mesna and cisplatin (VIP) or carboplatin (ICE)215 249 250 252 253 254 255 as second-line therapy for the treatment of refractory small-cell lung cancer.65 81 82 83 183 215 249 250 252 253 254 255

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In combination with cyclophosphamide and doxorubicin (or vincristine)61 69 70 71 72 73 86 190 199 200 201 for treatment of extensive-stage disease.253

Non-small Cell Lung Cancer

Combination chemotherapy with etoposide and cisplatin has been used for second-line treatment of advanced non-small cell lung cancer,93 94 95 96 204 205 but paclitaxel-containing 215 237 301 302 or other platinum-based regimens215 237 currently are preferred.

Hodgkin’s Disease

Component of combination chemotherapeutic regimens for treatment of advanced or refractory Hodgkin’s lymphoma.a 14 64 100 101 110 116 118 119 121 123 129

Non-Hodgkin’s Lymphoma

Component of various combination chemotherapeutic regimens for treatment of advanced non-Hodgkin’s lymphoma.13 14 54 64 100 101 115 116 117 118 119 120

Component of combination chemotherapeutic regimens (e.g., etoposide, ifosfamide, and methotrexate) for treatment of advanced diffuse lymphomas of unfavorable histology (e.g., diffuse histiocytic lymphoma).54 100 101 115 117 118 120 121 122 123 124 125 126 127

Cutaneous T-cell Lymphoma

Has been used with transient responses in patients with cutaneous T-cell lymphoma (mycosis fungoides).128

Acute Myeloid Leukemia

Used alone54 100 101 102 103 104 105 106 107 108 109 110 and in various combination chemotherapeutic regimens11 107 108 111 112 for treatment of refractory acute myeloid (myelogenous, nonlymphocytic) leukemia (AML, ANLL) in adults and children.14 34 54 67 100 101 102 103 104 105 106 107 108 109 110

Particularly effective for the treatment of acute monocytic and myelomonocytic leukemias;34 54 100 101 102 103 104 107 110 may be useful when monocytoid cells are not cleared with conventional combination chemotherapy.100 101 102 103 104 107 110

Acute Lymphocytic Leukemia

Has been used alone and in combination chemotherapy for remission induction in refractory acute lymphocytic (lymphoblastic) leukemia (ALL) in a limited number of children;108 109 110 little, if any, activity in adults.100 101 107

Wilms’ Tumor

Component of a combination chemotherapeutic regimen (e.g., carboplatin with etoposide) as second-line (salvage) therapy for treatment of recurrent (relapsed or refractory) Wilms’ tumor231 232 234 235 including recurrent tumors of unfavorable histology, abdominal recurrence after radiation therapy, or recurrence within 6 months of nephrectomy or after initial combination chemotherapy.231 232 239

Alternative to standard preferred regimens in patients with less severe stages of Wilms’ tumor.215

Second-line high-dose therapy followed by autologous bone marrow transplantation also has been used effectively in recurrent disease.231 232

Offer patients with recurrent disease (i.e., salvage therapy failure) treatment under protocol conditions in ongoing clinical trials.231

Neuroblastoma

Component of combination chemotherapeutic regimens (cyclophosphamide, doxorubicin, cisplatin, and/or etoposide or teniposide) as preferred first-line therapy for neuroblastoma.a 64 109 110 157 215 226 227 228 239

Kaposi’s Sarcoma

Used alone or in combination chemotherapeutic regimens257 258 259 as second-line therapya 133 215 258 for palliative treatment of AIDS-related Kaposi’s sarcoma. 215

Ovarian Cancer

Has been used orally as second-line therapy for advanced epithelial ovarian cancer.a 215 312 313 314 315 316

Component of a combination chemotherapeutic regimen with bleomycin and cisplatin (BEP) as first-line therapy for ovarian germ cell tumors.215 317 a

Other Uses

Component of alternating chemotherapeutic regimens (vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and mesna and etoposide) as first-line therapy for Ewing’s sarcoma.a 54 110 157

Component of a chemotherapeutic regimen with methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO), or with cisplatin as second-line therapy for gestational trophoblastic tumors (choriocarcinoma).a Also has been used for treatment of chorioadenoma destruens.130 185 a

May be useful for treatment of hepatoma.110 131 132

May be useful as second-line therapy for treatment of rhabdomyosarcoma.a 64 109 110

Etoposide Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.b c d (See IV Administration under Dosage and Administration.)

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer orally189 or IV.1 189 256

Intraperitoneal and intrapleural administration is not recommended; delayed, severe (sometimes fatal) toxicity has occurred in animals following administration by these routes. 139 155

Observe closely for possible hypotensive or anaphylactoid reactions during administration of the drug.1 (See Hypotension and also see Sensitivity Reactions, under Cautions.)

Oral Administration

Administer etoposide capsules orally.c

IV Administration

Administer diluted etoposide concentrate for injection by slow IV infusion.1 189

Administer etoposide phosphate by IV infusion.256

Use syringes with Luer-Lok fittings for handling of etoposide concentrate for injection;2 under pressure, needles have become displaced from etoposide-containing syringes without Luer-Lok fittings.2

Plastic devices composed of acrylic or ABS (a polymer composed of acrylonitrile, butadiene, and styrene) may crack and leak when used with undiluted etoposide injection.189

Etoposide solutions containing 0.1–0.4 mg/mL in 0.9% sodium chloride or 5% dextrose injection have been filtered through several commercially available filters (e.g., 0.22-mcm Millex-GS or Millex-GV) without filter decomposition.2 159

Reconstitution

Reconstitute vial containing 100 mg of etoposide phosphate powder with 5 or 10 mL sterile water for injection, 5% dextrose injection, 0.9% sodium chloride, bacteriostatic water for injection (with benzyl alcohol), or bacteriostatic sodium chloride for injection (with benzyl alcohol) to provide a solution containing 20 mg etoposide per mL (22.7 etoposide phosphate per mL) or 10 mg etoposide per mL (11.4 mg etoposide phosphate per mL), respectively.256

May administer reconstituted etoposide phosphate with or without further dilution.256

Dilution

Etoposide concentrate for injection must be diluted before administration.1 2 5 189

Dilute required dose of concentrate for injection to a final concentration of 0.2 or 0.4 mg/mL in 0.9% sodium chloride or 5% dextrose injection.1 2

Reconstituted etoposide phosphate solutions may be further diluted with either 5% dextrose injection or 0.9% sodium chloride injection to concentrations as low as 0.1 mg of etoposide per mL.256

Rate of Administration

Do not administer etoposide solutions by rapid IV injection.1 (See Hypotension under Cautions.)

Administer etoposide IV infusions over at least 30–60 minutes to minimize the risk of hypotensive reactions.1 If hypotensive reaction occurs, use slower rate of infusion if restarting after discontinuance and appropriate treatment.1 2

A longer duration of administration may be used if the volume of fluid to be infused is a concern.189

Has been administered by continuous IV infusion over 5 days,134 135 136 but no therapeutic advantage with this method over intermittent IV infusions.156

May administer etoposide phosphate solutions over 5–210 minutes.256

Dosage

Available as etoposide and etoposide phosphate; dosage is expressed in terms of etoposide; 113.6 mg of etoposide phosphate is equivalent to 100 mg of etoposide.296

Base dosage on the clinical and hematologic response and tolerance of the patient and whether or not other chemotherapy or radiation therapy has been or is also being used in order to obtain optimum therapeutic results with minimum adverse effects.1 2

Consult published protocols for the dosage, method, and sequence of administration of etoposide and other chemotherapeutic agents used in combination chemotherapeutic regimens.b

Do not administer a repeat course until the patient’s hematologic function is within acceptable limits.1

Toxicity profile of etoposide phosphate infused at doses exceeding 175 mg/m2 has not been delineated.256

Adults

Testicular Cancer
Induction of Remission for Refractory Testicular Neoplasms
IV

Combination chemotherapy regimens: Usually, 50–100 mg/m2 daily for 5 consecutive days every 3–4 weeks or 100 mg/m2 daily on days 1, 3, and 5 every 3–4 weeks,1 for 3 or 4 courses of therapy.38 43 44

When the consecutive-day dosage regimen is employed, some clinicians administer etoposide for 3–5 days, depending on the patient’s hematologic tolerance.38 43

Small Cell Lung Cancer
Oral

Twice the IV dosage rounded to the nearest 50 mg is recommended.189

IV

Combination chemotherapy regimens: Usually, ranges from 35 mg/m2 daily for 4 consecutive days to 50 mg/m2 daily for 5 consecutive days, every 3–4 weeks.188 256

Optimum duration not clearly defined; no additional improvement in survival when duration of therapy >3–6 months for limited-stage or >6 months for extensive-stage disease.253

Kaposi’s Sarcoma
AIDS-Related Kaposi’s Sarcoma
IV

150 mg/m2 daily for 3 consecutive days every 4 weeks; repeat cycles of therapy and reduce dosage as necessary depending on the patient’s response and the myelosuppressive effect of the drug.133

Special Populations

Hepatic Impairment

Use with caution; consider the need for dosage reduction.159 163 176

Renal Impairment

Clcr >50 mL/minute: no initial dose modification required.256

Clcr 15–50 mL/minute: administer 75% of the initial recommended dose.256

Clcr <15 mL/minute: consider further dose reduction; specific data are not available.256

Base subsequent doses on patient tolerance and clinical effect.256

Cautions for Etoposide

Contraindications

  • Known hypersensitivity to etoposide, etoposide phosphate, or any ingredient in the formulations.1 2 189 256

Warnings/Precautions

Warnings

Myelosuppression

Risk of dose-limiting and potentially fatal myelosuppression,1 2 17 59 64 106 110 116 118 120 133 134 135 136 256 manifested commonly by leukopenia (principally granulocytopenia);1 2 17 57 59 64 67 91 100 101 256 thrombocytopenia 1 2 17 64 67 91 100 101 and anemia may also occur.17 60 64 133 189 Severe myelosuppression with resulting infection or bleeding may occur.1 2 92 100 105 118 120 133 134 135 136

Granulocyte and platelet nadirs usually occur within 7–14 and 9–16 days, respectively, after administration of etoposide,1 2 59 67 106 134 136 and within 12–19 and 10–15 days, respectively, after administration of etoposide phosphate;256 leukocyte nadir usually occurs within 15–22 days after administration of etoposide phosphate.256 Bone marrow recovery is usually complete within 20 days after administration,1 2 56 60 67 134 135 but may occasionally require longer periods.17 106 136

Monitor hematologic function frequently during and after treatment.1 2 Perform CBC (leukocyte count with differential, platelet count, hemoglobin) prior to initiation of therapy, at appropriate intervals during the course of treatment (e.g., twice weekly),180 and before each subsequent course of treatment.1 2

Suspend therapy if the platelet count is <50,000/mm3 or absolute neutrophil count is <500/mm3.1 2 Resume therapy when blood counts have returned to an acceptable level, if indicated.1 2

If severe hematologic toxicity occurs, consider supportive therapy, antibiotics for complicating infections, and blood product transfusions.105 133 135 136

Hypotension

Transient hypotension reported following rapid IV administration of etoposide.1 2 57 110

Observe closely for possible hypotensive reactions.1

Administer IV infusions slowly (i.e., over at least 30–60 minutes) to minimize the risk of hypotensive reactions.1

Hypotension occurring during administration usually subsides with infusion discontinuance, administration of IV fluids or other supportive therapy as necessary.1 2

Use slower rate of infusion if restarting after discontinuance and appropriate treatment.1 2

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.c d Avoid pregnancy during therapy.c d If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.c d

Carcinogenicity

Acute leukemia (with or without a preleukemic phase) has been reported rarely in patients receiving etoposide in association with other antineoplastic agents.189 256

Animal studies to determine the carcinogenic potential of etoposide have not been performed to date;1 256 however, the drug should be considered a potential carcinogen.1

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions consisting principally of chills,1 2 67 92 256 rigors,256 diaphoresis,64 256 pruritus,256 loss of consciousness,256 nausea,256 vomiting,256 fever,1 2 bronchospasm,1 2 178 256 dyspnea,1 2 141 178 256 tachycardia,1 2 256 hypertension,189 256 and/or hypotension1 2 92 178 256 reported.1 2 67 92 134 178 256

Observe closely for possible anaphylactic reactions.1

Appropriate equipment for maintenance of an adequate airway and other supportive measures and agents for the treatment of these reactions should be readily available whenever etoposide is administered.1

Stevens-Johnson syndrome,256 rash,1 2 189 256 pigmentation,189 urticaria,189 256 and severe pruritus64 189 256 occur infrequently.1 2 142 179

If a hypersensitivity reaction occurs during administration, discontinue infusion and institute appropriate therapy (e.g., antihistamines, epinephrine, oxygen, corticosteroids) as necessary.1

The role of infusion concentration or rate in the development of hypersensitivity reactions is uncertain.189 256

General Precautions

Toxicity

Highly toxic drug with a low therapeutic index; therapeutic response is not likely to occur without some evidence of toxicity.1 2 34 139

Administer only under constant supervision by clinicians experienced in therapy with cytotoxic agents and only when the potential benefits outweigh the possible risks.1

Most adverse effects are reversible if detected promptly.1

Discontinue or reduce dosage and institute appropriate measures as necessary when severe adverse effects occur.1

Reinstitute therapy with caution, considering further need for the drug and possible toxicity recurrence.1

Specific Populations

Pregnancy

Category D.c (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether etoposide is distributed into milk.1 Discontinue nursing or the drug.1

Pediatric Use

Safety and efficacy not established.1 256

Higher rates of anaphylactoid reactions reported in children receiving infusions at higher than recommended concentrations.189 256 (See Hypersensitivity Reactions under Cautions.)

Has been used with encouraging results for refractory acute myelogenous leukemia,11 108 109 110 112 has shown some activity against refractory acute lymphocytic leukemia108 110 and other pediatric malignancies,109 110 157 but additional evaluation is needed.108 109 110 157

Each mL of etoposide concentrate for injection contains 30 mg of benzyl alcohol.c Although a causal relationship has not been established, injections preserved with benzyl alcohol have been associated with toxicity in neonates.216 217 218 219 220 221

Concentrate for injection contains polysorbate 80A complex; potentially fatal syndrome (e.g., thrombocytopenia, ascites, and renal, pulmonary, and hepatic failure) has occurred in several premature infants who received a vitamin E product (IV) with polysorbate 80.189

Hepatic Impairment

Effects of hepatic impairment on etoposide elimination have not been fully evaluated.20 21 28 163 176 197

Toxicity of rapidly infused etoposide phosphate in hepatic impairment has not been adequately evaluated.256

Use with caution, consider the need for dosage reduction; more severe hematologic toxicity reported with elevated serum bilirubin concentrations in one study.163 Some evidence of reduced total plasma clearance and elimination.28 159 163 176

Renal Impairment

Dosage adjustments recommended based on degree of renal impairment.20 21 161 256 (See Renal Impairment under Dosage and Administration.)

Toxicity of rapidly infused etoposide phosphate in renal impairment has not been adequately evaluated.256

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy for treatment of testicular tumors in geriatric patients differ from safety and efficacy in younger adults.f

Response in patients ≥65 years of age with small cell lung cancer similar to that in younger adults.f

Substantially eliminated by kidneys; assess renal function periodically since geriatric patients more likely to have decreased renal function.f Dosage adjustments may be required.f (See Renal Impairment under Dosage and Administration.)

Geriatric patients may be particularly susceptible to etoposide-induced adverse effects.137

Common Adverse Effects

Leukopenia,1 2 17 57 59 64 67 91 100 101 256 thrombocytopenia,1 2 17 64 67 91 100 101 neutropenia,256 anemia,17 60 64 133 189 nausea,1 2 17 60 67 91 100 109 189 256 vomiting,1 2 17 60 67 91 100 109 189 256 anorexia,1 2 67 92 101 116 134 256 mucositis,256 diarrhea,1 2 109 134 136 256 alopecia,1 2 17 60 64 67 100 101 109 133 134 189 256 asthenia/malaise,c fatigue,1 2 chills and/or fever.c

Interactions for Etoposide

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents (cisplatin, carmustine, cytarabine, cyclophosphamide)

Potential additive or synergistic antineoplastic activity43 44 65 79 80 81 82 83 152 153 154

Cisplatin

Possible decreased etoposide elimination176

Limited data, further documentation needed; consider potential effect when administering etoposide to patients who received prior cisplatin therapy176

Cyclosporine (high-dose)

Possible decreased total body clearance of etoposide with concomitant use of oral etoposide and high-dose cyclosporine 256

Inhibitors of phosphatase activity (e.g., levamisole HCl)

Use caution with etoposide phosphate256

Etoposide Pharmacokinetics

Absorption

Bioavailability

Oral capsules: about 50% (range: 25–75%).17 18 19 160 161 189 190 191 192 193 194 195 196 197

Distribution

Extent

Not fully characterized.18 21 24 27 28 Following IV administration, distributed minimally into pleural fluid21 27 and has been detected in the saliva,197 liver,173 spleen,173 kidney,173 myometrium,189 197 healthy brain tissue,27 and brain tumor tissue.27 175

Does not readily penetrate the CNS;1 18 21 22 27 29 30 197 variable CSF concentrations generally ranging from undetectable18 22 to <5% of concurrent plasma concentrations21 29 30 162

Apparently crosses the placenta in animals,1 2 not known whether distributed into milk.1

Plasma Protein Binding

Approximately 97% at 10 mcg/mL in vitro.c f

Elimination

Metabolism

Metabolized principally to inactive hydroxy acid21 25 26 30 32 33 177 (probably the trans-hydroxy acid).33

Elimination Route

Following IV infusion, excreted principally (40–60%) in urine as unchanged drug (20–30% within 24 hours,18 29 30 30–45% within 48 hours)20 161 and metabolites in 48–72 hours.18 20 21 26 27 29 30 32 2–16% is excreted in feces within 72 hours;29 30 .28 173 174 197

Following oral administration, about 5–25% of the dose is excreted in urine within 24–48 hours.191 194 195 196 197

Half-life

Biphasic,18 21 22 24 25 27 29 30 31 176 197 may exhibit triphasic elimination with a prolonged terminal phase.19 197

In adults, 0.6–2 hours (range: 0.2–2.5 hours) in the initial phase and 5.3–10.8 hours (range: 2.9–19 hours) in the terminal phase.18 20 21 24 29 161 189 191 192

In children, 0.6–1.4 hours in the initial phase and 3–5.8 hours in the terminal phase.18 22 25 31

Special Populations

The effects of renal impairment on elimination have not been fully evaluated,20 21 28 163 176 197 but a substantial fraction of the drug is excreted unchanged in urine;18 20 21 29 30 161 176 256 consider dosage reductions.b (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Capsules

2–8°C.189 Do not freeze.c Stable for 2 years refrigerated at 2–8°C.189

Parenteral

Etoposide Injection Concentrate for IV Infusion

Room temperature (25°C).1 Stable for 2 years unopened at room temperature.1

Following dilution to concentrations of 0.2 or 0.4 mg/mL, stable for 96 or 24 hours, respectively, at 25°C under normal room fluorescent light in glass or plastic containers.c

Etoposide Phosphate Lyophilized Powder for Injection

2–8°C; store in unopened vials in original package to protect from light;256 296 stable at least 36 months.296

Following reconstitution, 10 or 20 mg/mL solutions of etoposide phosphate in sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection, bacteriostatic water for injection (with benzyl alcohol) or bacteriostatic sodium chloride for injection (with benzyl alcohol) are stable for 7 days at 2–8°C in glass or plastic containers.d

10 or 20 mg/mL solutions of etoposide phosphate in sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection are stable for 24 hours at 20–25°C.d

10 or 20 mg/mL solutions of etoposide phosphate in bacteriostatic water for injection (with benzyl alcohol) or bacteriostatic sodium chloride for injection (with benzyl alcohol) are stable for 48 hours at 20–25°C.d

Etoposide phosphate solutions further diluted in 5% dextrose injection or 0.9% sodium chloride injection are stable for 24 hours at 2–8°C or 20–25°C.d

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Injection Concentrate for IV Infusion

Crystallization in aqueous solutions appears to be concentration dependent and may occur following dilution because etoposide is sparingly soluble in water;1 2 5 discard if crystallization occurs.5

Solutions of etoposide prepared at concentrations >0.4 mg/mL may precipitate; 189 concentration >0.4 mg/mL not recommended.1 2 189 c

1 mg/mL solutions in 5% dextrose injection or 0.9% sodium chloride have crystallized etoposide within 5 minutes upon stirring or within 30 minutes upon allowing the solution to stand;5 1 mg/mL solutions not recommended.5

Solution CompatibilityHID (etoposide)

Compatible

Dextrose 5% in water

Ringer’s injection, lactated

Variable

Sodium chloride 0.9%

Drug Compatibility (etoposide)
Admixture CompatibilityHID

Compatible

Carboplatin

Cisplatin

Cisplatin with cyclophosphamide

Cisplatin with floxuridine

Cytarabine with daunorubicin HCl

Floxuridine

Fluorouracil

Hydroxyzine HCl

Ifosfamide

Ifosfamide with cisplatin

Mitoxantrone HCl

Ondansetron HCl

Variable

Cisplatin with mannitol and potassium chloride

Doxorubicin HCl with vincristine sulfate

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Amifostine

Aztreonam

Cladribine

Doxorubicin HCl liposome injection

Fludarabine phosphate

Gemcitabine HCl

Granisetron HCl

Melphalan HCl

Methotrexate sodium

Micafungin sodium

Mitoxantrone HCl

Ondansetron HCl

Paclitaxel

Piperacillin sodium–tazobactam sodium

Sargramostim

Sodium bicarbonate

Teniposide

Thiotepa

Topotecan HCl

Vinorelbine tartrate

Incompatible

Filgrastim

Gallium nitrate

Idarubicin HCl

Solution CompatibilityHID (etoposide phosphate)

Compatible

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility (etoposide phosphate)
Admixture CompatibilityHID

Compatible

Doxorubicin HCl with vincristine sulfate

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Amikacin sulfate

Aminophylline

Ampicillin sodium

Ampicillin sodium–sulbactam sodium

Anidulafungin

Aztreonam

Bleomycin sulfate

Bumetanide

Buprenorphine HCl

Butorphanol tartrate

Calcium gluconate

Carboplatin

Carmustine

Caspofungin acetate

Cefazolin sodium

Cefotaxime sodium

Cefotetan disodium

Cefoxitin sodium

Ceftazidime

Ceftriaxone sodium

Cefuroxime sodium

Ciprofloxacin

Cisplatin

Clindamycin phosphate

Co-trimoxazole

Cyclophosphamide

Cytarabine

Dacarbazine

Dactinomycin

Daunorubicin HCl

Dexamethasone sodium phosphate

Diphenhydramine HCl

Dobutamine HCl

Dopamine HCl

Doripenem

Doxorubicin HCl

Doxycycline hyclate

Droperidol

Enalaprilat

Famotidine

Floxuridine

Fluconazole

Fludarabine phosphate

Fluorouracil

Furosemide

Ganciclovir sodium

Gemcitabine HCl

Gentamicin sulfate

Granisetron HCl

Haloperidol lactate

Heparin sodium

Hydrocortisone sodium succinate

Hydromorphone HCl

Hydroxyzine HCl

Idarubicin HCl

Ifosfamide

Leucovorin calcium

Linezolid

Lorazepam

Magnesium sulfate

Mannitol

Meperidine HCl

Mesna

Methotrexate sodium

Metoclopramide HCl

Metronidazole

Mitoxantrone HCl

Morphine sulfate

Nalbuphine HCl

Ondansetron HCl

Oxaliplatin

Paclitaxel

Piperacillin sodium–tazobactam sodium

Potassium chloride

Promethazine HCl

Ranitidine HCl

Sodium bicarbonate

Streptozocin

Teniposide

Thiotepa

Ticarcillin disodium–clavulanate potassium

Tobramycin sulfate

Vancomycin HCl

Vinblastine sulfate

Vincristine sulfate

Zidovudine

Incompatible

Amphotericin B

Cefepime HCl

Chlorpromazine HCl

Imipenem–cilastatin sodium

Methylprednisolone sodium succinate

Mitomycin

Prochlorperazine edisylate

Actions

  • Exact mechanism(s) of action is not known; apparently produces cytotoxic effects by damaging DNA3 6 7 169 170 and thereby inhibiting or altering DNA synthesis.1 2 3 8 169

  • Induces single-stranded DNA breaks indirectly, possibly through endonuclease activation,6 7 inhibition of intranuclear type II topoisomerase,170 171 172 or formation of a free-radical metabolite via an enzymatic reaction involving the hydroxyl group at the C-4′ position of the E ring.6 7

  • Cell-cycle dependent and cycle-phase specific, inducing G2-phase arrest, and preferentially killing cells in the G2 and late S phases.8 9 10 11 169

  • At 0.3–10 mcg/mL in vitro, cells are inhibited from entering prophase;1 at concentrations of ≥10 mcg/mL, lysis of cells entering mitosis occurs.1 Does not inhibit microtubule assembly.1 2 3 12 167

Advice to Patients

  • Importance of advising patients and/or their parents or guardians of adverse effects and associated manifestations.a

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.a

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.a

  • Importance of informing patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Etoposide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

50 mg

Etoposide Capsules

VePesid

Bristol-Myers Squibb

Parenteral

For injection concentrate, for IV infusion only

20 mg/mL (100, 150, 200, 250, and 500 mg)*

Etoposide for Injection

Toposar

Pfizer

VePesid

Bristol-Myers Squibb

20 mg/mL (1 g) pharmacy bulk package*

Etoposide for Injection

VePesid

Bristol-Myers Squibb

Etoposide Phosphate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

500 mg (of etoposide) pharmacy bulk package

Etopophos

Bristol-Myers Squibb

1 g (of etoposide) pharmacy bulk package

Etopophos

Bristol-Myers Squibb

For injection, for IV infusion

100 mg (of etoposide)

Etopophos

Bristol-Myers Squibb

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 9, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Bristol Laboratories. VePesid prescribing information. Syracuse, NY; 1983 Nov.

2. Bristol Laboratories. VePesid (etoposide) product information overview. Syracuse, NY; 1983 Nov. CPE-259.

3. Loike JD. VP16-213 and podophyllotoxin: a study on the relationship between chemical structure and biological activity. Cancer Chemother Pharmacol. 1982; 7:103-11. [PubMed 7044591]

4. Reynolds JEF, ed. Martindale: the extra pharmacopoeia. 28th ed. London: The Pharmaceutical Press; 1982:208.

5. National Cancer Institute. NCI investigational drugs. NIH Publ. No. 83-2141. Washington, DC: US Government Printing Office; 1983:107-9. Available from: National Cancer Institute, Silver Spring, MD.

6. Wozniak AJ, Ross WE. DNA damage as a basis for 4′-demethylepipodophyllotoxin-9-(4,6-O-ethylidene-β-d-glucopyranoside) (etoposide) cytotoxicity. Cancer Res. 1983; 43:120-4. [PubMed 6847761]

7. Loike JD, Horwitz SB. Effect of VP-16-213 on the intracellular degradation of DNA in HeLa cells. Biochemistry. 1976; 15:5443-8. [PubMed 999819]

8. Drewinko B, Barlogie B. Survival and cycle-progression delay of human lymphoma cells in vitro exposed to VP-16-213. Cancer Treat Rep. 1976; 60:1295-306. [IDIS 75077] [PubMed 1016966]

9. Grieder A, Maurer R, Stahelin H. Effect of an epipodophyllotoxin derivative (VP 16-213) on macromolecular synthesis and mitosis in mastocytoma cells in vitro. Cancer Res. 1974; 34:1788-93. [PubMed 4210356]

10. Krishan A, Paika K, Frei E III. Cytofluorometric studies on the action of podophyllotoxin and epipodophyllotoxins (VM-26, VP-16-213) on the cell cycle traverse of human lymphoblasts. J Cell Biol. 1975; 66:521-30. [PubMed 1057547]

11. Look AT, Dahl GV, Rivera G et al. Clinical and cell kinetic studies of the effects of the epipodophyllotoxin VP16-213 during therapy of refractory acute nonlymphocytic leukemia. Cancer Chemother Pharmacol. 1982; 7:161-7. [IDIS 178830] [PubMed 6177437]

12. Loike JD, Horwitz SB. Effects of podophyllotoxin and VP-16-213 on microtubule assembly in vitro and nucleoside transport in HeLa cells. Biochemistry. 1976; 15:5435-43. [PubMed 999818]

13. Nissen NI, Hansen HH, Pedersen H et al. Clinical trial of the oral form of a new podophyllotoxin derivative, VP-16-213 (NSC-141540) in patients with advanced neoplastic disease. Cancer Chemother Rep. 1975; 59:1027-9. [IDIS 63092] [PubMed 1106845]

14. Falkson G, van Dyk JJ, van Eden EB et al. A clinical trial of the oral form of 4′-demethyl-epipodophyllotoxin-β-d ethylidene glucoside (NSC 141540) VP 16-213. Cancer. 1975; 35:1141-4. [IDIS 53744] [PubMed 163675]

15. Brunner KW, Sonntag RW, Ryssel HJ et al. Comparison of the biologic activity of VP-16-213 given IV and orally in capsules or drink ampules. Cancer Treat Rep. 1976; 60:1377-9. [IDIS 75082] [PubMed 1016971]

16. Nissen NI, Dombernowsky P, Hansen HH et al. Phase I clinical trial of an oral solution of VP-16-213. Cancer Treat Rep. 1976; 60:943-5. [IDIS 70926] [PubMed 1009527]

17. Lau ME, Hansen HH, Nissen NI et al. Phase I trial of a new form of an oral administration of VP-16-213. Cancer Treat Rep. 1979; 63:485-7. [IDIS 100735] [PubMed 371801]

18. D’Incalci M, Farina P, Sessa C et al. Pharmacokinetics of VP16-213 given by different administration methods. Cancer Chemother Pharmacol. 1982; 7:141-5. [PubMed 7083454]

19. Arnold AM, Dodson M, Renwick A et al. Pharmacokinetics of VP 16-213 using a new HPLC assay. Cancer Chemother Pharmacol. 1980; 5(Suppl 2):2.

20. Scalzo AJ, Comis R, Fitzpatrick A et al. VP-16 pharmacokinetics in adults with cancer as determined by a new high-pressure liquid chromatography (HPLC) assay. Proc Am Soc Clin Oncol. 1982; 1:129.

21. Hande KR, Wedlund PJ, Noone RM et al. Pharmacokinetics of high-dose etoposide (VP-16-213) administered to cancer patients. Cancer Res. 1984; 44:379-82. [IDIS 179642] [PubMed 6690051]

22. Evans WE, Sinkule JA, Horvath A et al. Clinical pharmacology of VM-26 (NSC 122819) and VP-16 (NSC 141540) in children with cancer. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1981; 22:174.

23. Colombo T, Broggini M, Torti L et al. Pharmacokinetics of VP16-213 in Lewis lung carcinoma bearing mice. Cancer Chemother Pharmacol. 1982; 7:127-31. [PubMed 7083453]

24. Allen LM, Creaven PJ. Comparison of the human pharmacokinetics of VM-26 and VP-16, two antineoplastic epipodophyllotoxin glucopyranoside derivatives. Eur J Cancer. 1975; 11: 697-707. [IDIS 178819] [PubMed 1204664]

25. Evans WE, Sinkule JA, Crom WR et al. Pharmacokinetics of teniposide (VM26) and etoposide (VP16-213) in children with cancer. Cancer Chemother Pharmacol. 1982; 7:147-50. [IDIS 178827] [PubMed 7083455]

26. Pelsor FR, Allen LM, Creaven PJ. Multicompartment pharmacokinetic model of 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside) in humans. J Pharm Sci. 1978; 67:1106-8. [IDIS 86402] [PubMed 671246]

27. Lu K, Savaraj N, Feun L et al. Clinical pharmacology and intracerebral tumor penetration of 4′-demethyl epipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside) (VP-16, NSC-141540). Clin Pharmacol Ther. 1982; 31:245.

28. D’Incalci M, Sessa C, Farina P et al. Clinical pharmacokinetics of VP16. Proc Annu Meet Am Soc Clin Oncol. 1982; 23:131.

29. Creaven PJ, Allen LM. EPEG, a new antineoplastic epipodophyllotoxin. Clin Pharmacol Ther. 1975; 18:221-6. [IDIS 60555] [PubMed 1157446]

30. Creaven PJ. The clinical pharmacology of VM26 and VP16-213: a brief overview. Cancer Chemother Pharmacol. 1982; 7:133-40. [IDIS 178825] [PubMed 7044592]

31. Snodgrass W, Walker L, Heideman R et al. Kinetics of VP-16 epipodophyllotoxin in children with cancer. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1980; 21:333.

32. Allen LM, Marcks C, Creaven PJ et al. 4′-Demethyl-epipodophyllic acid-9-(4,6,-O-ethylidene-β-d-glucopyranoside), the major urinary metabolite of VP-16-213 in man. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1976; 17:6.

33. Strife J, Jardine I. Analysis of the anticancer drugs VP 16-213 and VM 26 and their metabolites by high-performance liquid chromatography. J Chromatogr. 1980; 182:211-20. [IDIS 178818] [PubMed 7380913]

34. Vogelzang NJ, Raghavan D, Kennedy BJ. VP-16-213 (etoposide): the mandrake root from Issyk-Kul. Am J Med. 1982; 72:136-44. [IDIS 143620] [PubMed 6277188]

35. Newlands ES, Bagshawe KD. Epipodophyllin derivative (VP16-213) in malignant teratomas and choriocarcinomas. Lancet. 1977; 2:87. [IDIS 75671] [PubMed 69168]

36. Cavalli F, Sonntag RW, Brunner KW. Epipodophyllotoxin derivative (VP 16-213) in treatment of solid tumors. Lancet. 1977; 2:362. [IDIS 76051] [PubMed 69974]

37. Fitzharris BM, Kaye SB, Saverymuttu S et al. VP16-213 as a single agent in advanced testicular tumors. Eur J Cancer. 1980; 16:1193-7. [PubMed 7227446]

38. Williams SD, Einhorn LH, Greco FA et al. VP-16-213 salvage therapy for refractory germinal neoplasms. Cancer. 1980; 46:2154-8. [IDIS 127403] [PubMed 6159062]

39. Einhorn LH. Testicular cancer as a model for a curable neoplasm: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res. 1981; 41:3275-80. [IDIS 139877] [PubMed 6167346]

40. Hainsworth JD, Greco FA. Testicular germ cell neoplasms. Am J Med. 1983; 75:817-32. [IDIS 177683] [PubMed 6195919]

41. Einhorn LH, Williams SD, Mandelbaum I et al. Surgical resection in disseminated testicular cancer following chemotherapeutic cytoreduction. Cancer. 1981; 48:904-8. [PubMed 6168361]

42. Vugrin D, Whitmore WF Jr, Sogani PC et al. Combined chemotherapy and surgery in treatment of advanced germ-cell tumors. Cancer. 1981; 47:2228-31. [IDIS 132343] [PubMed 7226117]

43. Williams SD, Einhorn LH. Etoposide salvage therapy for refractory germ cell tumors: an update. Cancer Treat Rev. 1982; 9(Suppl. A):67-71. [PubMed 6290056]

44. Mortimer J, Bukowski RM, Montie J et al. VP16-213, cisplatinum, and adriamycin salvage therapy of refractory and/or recurrent nonseminomatous germ cell neoplasms. Cancer Chemother Pharmacol. 1982; 7:215-8. [IDIS 178841] [PubMed 6282486]

45. Peckham MJ, Barrett A, Liew KH et al. The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cis-platin (BEP). Br J Cancer. 1983; 47:613-9. [IDIS 178814] [PubMed 6189504]

46. Peckham MJ, Barrett A, Horwich A et al. Treatment of testicular tumours. Lancet. 1983; 1:1334-5.

47. Ozols RF, Deisseroth AB, Javadpour N et al. Treatment of poor prognosis nonseminomatous testicular cancer with a “high-dose” platinum combination chemotherapy regimen. Cancer. 1983; 51:1803-7. [IDIS 170158] [PubMed 6187426]

48. Ozols RF, Corden BJ, Jacob J et al. High-dose cisplatin in hypertonic saline. Ann Intern Med. 1984; 100:19-24. [IDIS 179877] [PubMed 6197916]

49. Read G, Johnson RJ, Wilkinson PM et al. Prospective study of follow up alone in stage I teratoma of the testis. BMJ. 1983; 287:1503-5. [PubMed 6196076]

50. Ball D, Barrett A, Peckham MJ et al. The management of metastatic seminoma testis. Cancer. 1982; 50:2289-94. [IDIS 162323] [PubMed 6182973]

51. Wajsman Z, Beckley SA, Pontes JE. Changing concepts in the treatment of advanced seminomatous tumors. J Urol. 1983; 129:303-5. [IDIS 168643] [PubMed 6187944]

52. Bukowski RM, Montie J, Livingston RB et al. Combination chemotherapy including VP-16 in poor prognosis germinal cell neoplasms. Proc Annu Meet Am Soc Clin Oncol. 1982; 23:153.

53. Vogelzang NJ, Kennedy BJ. “Salvage” chemotherapy for refractory germ cell tumors. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1981; 22:471.

54. Schmoll H. Review of etoposide single-agent activity. Cancer Treat Rev. 1982; 9(Suppl A):21-30. [PubMed 6751532]

55. Bunn PA Jr. Lung cancer: the current approach to diagnosis, staging and treatment. Syracuse, NY: Bristol Laboratories. 1983 Nov. CPE-273B.

56. Eagan RT, Carr DT, Frytak S et al. VP-16-213 versus polychemotherapy in patients with advanced small cell cancer. Cancer Treat Rep. 1976; 60:949-51. [IDIS 70928] [PubMed 64298]

57. Cohen MH, Broder LE, Fossieck BE et al. Phase II clinical trial of weekly administration of VP-16-213 in small cell bronchogenic carcinoma. Cancer Treat Rep. 1977; 61:489-90. [IDIS 86765] [PubMed 194694]

58. Hansen M, Hirsch F, Dombernowsky P et al. Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP-16-213 (NSC 141540, 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside)). Cancer. 1977; 40:633-7. [IDIS 91640] [PubMed 196736]

59. Cavalli F, Sonntag RW, Jungi F et al. VP-16-213 monotherapy for remission induction of small cell lung cancer: a randomized trial using three dosage schedules. Cancer Treat Rep. 1978; 62:473-5. [IDIS 103257] [PubMed 348319]

60. Tucker RD, Ferguson A, Van Wyk C et al. Chemotherapy of small cell carcinoma of the lung with V.P. 16-213. Cancer. 1978; 41:1710-4. [IDIS 91567] [PubMed 206338]

61. Goldhirsch A, Joss R, Cavalli F et al. Etoposide as single agent and in combination chemotherapy of bronchogenic carcinoma. Cancer Treat Rev. 1982; 9(Suppl A):85-90. [IDIS 178613] [PubMed 6290057]

62. Asbury RF, Rubins J, Bennett JM. Etoposide in small cell lung cancer resistant to prior chemotherapy. Cancer Treat Rep. 1983; 67:951-2. [IDIS 178384] [PubMed 6313187]

63. Wolff SN, Johnson DH, Hande KR et al. High-dose etoposide as single-agent chemotherapy for small cell carcinoma of the lung. Cancer Treat Rep. 1983; 67:957-8. [IDIS 178387] [PubMed 6313189]

64. Nissen NI, Pajak TF, Leone LA et al. Clinical trial of VP 16-213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B. Cancer. 1980; 45:232-5. [IDIS 109053] [PubMed 6985831]

65. Evans WK, Feld R, Osoba D et al. VP-16 alone and in combination with cisplatin in previously treated patients with small cell lung cancer. Cancer. 1984; 53:1461-6. [IDIS 183322] [PubMed 6321006]

66. Tempero M, Kessinger A, Lemon HM. VP-16-213 therapy in patients with small-cell carcinoma of the lung after failure on combination chemotherapy. Cancer Clin Trials. 1981; 4:155-7. [IDIS 178602] [PubMed 6265110]

67. Jungi WF, Senn HJ. Clinical study of the new podophyllotoxin derivative, 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside) (NSC-141540; VP-16-213), in solid tumors in man. Cancer Chemother Rep. 1975; 59(4 Part 1):737-42. [PubMed 1100224]

68. Estape J, Milla A, Agusti A et al. VP-16 plus cyclophosphamide in the treatment of advanced lung cancer. Cancer. 1983; 51:385-9. [IDIS 167843] [PubMed 6295601]

69. Klastersky J, Nicaise C, Longeval E et al. Cisplatin, adriamycin, and etoposide (CAV) for remission induction of small-cell bronchogenic carcinoma: evaluation of efficacy and toxicity and pilot study of a “late intensification” with autologous bone-marrow rescue. Cancer. 1982; 50:652-8. [IDIS 156009] [PubMed 6284335]

70. Vincent RG, Wilson HE, Lane WW et al. Progress in the chemotherapy of small cell carcinoma of the lung. Cancer. 1981; 47:229-35. [IDIS 130777] [PubMed 6257374]

71. Abeloff MD, Ettinger DS, Order SE et al. Intensive induction chemotherapy in 54 patients with small cell carcinoma of the lung. Cancer Treat Rep. 1981; 65:639-46. [IDIS 136986] [PubMed 6265082]

72. Aisner JA, Whitacre M, Van Echo DA et al. Doxorubicin, cyclophosphamide, and VP16-213 (ACE) in the treatment of small cell lung cancer. Cancer Chemother Pharmacol. 1982; 7:187-93. [IDIS 178834] [PubMed 6282482]

73. Aisner J, Wiernik PH. Chemotherapy versus chemoimmunotherapy for small-cell undifferentiated carcinoma of the lung. Cancer. 1980; 46:2543-9. [IDIS 129132] [PubMed 6256048]

74. Goodman GE, Miller TP, Manning MM et al. Treatment of small cell lung cancer with VP-16, vincristine, doxorubicin (adriamycin), cyclophosphamide (EVAC), and high-dose chest radiotherapy. J Clin Oncol. 1983; 1:483-8. [PubMed 6321685]

75. von Eyben FE, Arwidi A, Hellekant C et al. Vincristine, adriamycin, cyclophosphamide, and etoposide (VP16-213) in small-cell anaplastic carcinoma of the lung. Cancer Chemother Pharmacol. 1982; 7:195-7. [IDIS 178835] [PubMed 6282483]

76. Messeih A, Schweitzer JM, Dixon RH et al. The addition of VP16-213 to cytoxan, adriamycin and vincristine for remission induction, and survival in patients with small cell lung cancer. Proc Am Soc Clin Oncol. 1983; 2:201.

77. Jackson DV, Ferree CF, White DR et al. Cytoxan, adriamycin, and vincristine (CAV) versus VP16-213 + CAV (VCAV) in the treatment of small cell carcinoma of the lung (SCC). Proc Am Soc Clin Oncol. 1982; 1:154.

78. Newman SB, Bitran JD, Golomb HM et al. VP16-213 in combined modality treatment of small cell carcinoma of the lung. Eur J Cancer Clin Oncol. 1982; 18:343-6. [IDIS 178820] [PubMed 6288390]

79. Sierocki JS, Hilaris BS, Hopfan S et al. cis-Dichlorodiammineplatinum(II) and VP-16-213: an active induction regimen for small cell carcinoma of the lung. Cancer Treat Rep. 1979; 63:1593-7. [IDIS 109334] [PubMed 227598]

80. Natale RB, Wittes RE. Combination cis-platinum and etoposide in small-cell lung cancer. Cancer Treat Rev. 1982; 9(Suppl A):91-4. [IDIS 178614] [PubMed 6290058]

81. Madrigal PA, Manga GP, Palomero I et al. VP16-213 combined with cis-platinum (CDDP) in the treatment of small cell carcinoma of the lung (SCLC). Cancer Chemother Pharmacol. 1982; 7:203-4. [IDIS 178837] [PubMed 6282485]

82. Kim PN, McDonald DB. The combination of VP 16-213 and cis-platinum in the treatment of small cell carcinoma of lung. Proc Am Soc Clin Oncol. 1982; 1:141.

83. Tinsley R, Comis R, Difino S et al. Potential clinical synergy observed in the treatment of small cell lung cancer (SCLS) with cisplatin (P) and VP-16-213 (V). Proc Am Soc Clin Oncol. 1983; 2:198.

84. Eagan RT, Frytak S, Nichols WC et al. Cyclophosphamide and VP-16-213 with or without cisplatin in squamous cell and small cell lung cancers. Cancer Treat Rep. 1981; 65:453-8. [IDIS 140207] [PubMed 6263477]

85. Broder LE, Selawry OS, Charyulu KN et al. A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung. Chest. 1981; 79:327-35. [IDIS 149026] [PubMed 6258871]

86. Aisner J, Whitacre M, Van Echo DA et al. Combination chemotherapy for small cell carcinoma of the lung: continuous versus alternating non-cross-resistant combinations. Cancer Treat Rep. 1982; 66:221-30. [IDIS 145459] [PubMed 6275987]

87. Aroney RS, Bell DR, Chan WK et al. Alternating non-cross-resistant combination chemotherapy for small cell anaplastic carcinoma of the lung. Cancer. 1982; 49:2449-54. [IDIS 152478] [PubMed 6280840]

88. Osterlind K, Sorenson S, Hansen HH et al. Continuous versus alternating combination chemotherapy for advanced small cell carcinoma of the lung. Cancer Res. 1983; 43:6085-9. [IDIS 178550] [PubMed 6315227]

89. Cardenal F, Lopez-Cabrerizo MP, Anton A et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastic non-small-cell lung cancer. J Clin Oncol. 1999; 17:12-8. [IDIS 419947] [PubMed 10458212]

90. Itri LM, Gralla RJ. A review of etoposide in patients with non-small-cell lung cancer (NSCLC). Cancer Treat Rev. 1982; 9(Suppl A):115-8. [IDIS 178619] [PubMed 6889916]

91. Eagan RT, Ingle JN, Creagan ET et al. VP-16-213 chemotherapy for advanced squamous cell carcinoma and adenocarcinoma of the lung. Cancer Treat Rep. 1978; 62:843-4. [IDIS 94759] [PubMed 657168]

92. Chapman R, Itri L, Gralla R et al. Phase II trial of VP16-213 in non-small cell lung cancer (NSCLC). Cancer Chemother Pharmacol. 1982; 7:205-7. [IDIS 178838] [PubMed 7083460]

93. Longeval E, Klastersky J. Combination chemotherapy with cisplatin and etoposide in bronchogenic squamous cell carcinoma and adenocarcinoma: a study by the EORTC Lung Cancer Working Party (Belgium). Cancer. 1982; 50:2751-6. [IDIS 163030] [PubMed 6890404]

94. Mitrou PS, Graubner M, Berdel WE et al. cis-Platinum (DDP) and VP 16-213 (etoposide) combination chemotherapy for advanced non-small cell lung cancer. A phase II clinical trial. Eur J Cancer Clin Oncol. 1984; 20:347-51. [PubMed 6538496]

95. Klastersky J, Longeval E, Nicaise C et al. Etoposide and cis-platinum in non-small-cell bronchogenic carcinoma. Cancer Treat Rev. 1982; 9(Suppl. A):133-8. [IDIS 178621] [PubMed 6889918]

96. Veronesi A, Zagonel V, Santarossa M et al. cis-Platinum and etoposide combination chemotherapy of advanced non-oat cell bronchogenic carcinoma. Cancer Chemother Pharmacol. 1983; 11:35-7. [IDIS 178816] [PubMed 6683999]

97. Eagan RT, Creagan ET, Ingle JN et al. VP-16, cyclophosphamide, adriamycin, and cis-platinum (V:CAP-I) in patients with metastatic adenocarcinoma of the lung. Tumori. 1979; 65:105-9. [PubMed 442215]

98. Eagan RT, Frytak S, Nichols WC et al. Evaluation of VP-16-213, cyclophosphamide, doxorubicin, and cisplatin (V-CAP) in advanced large cell lung cancer. Cancer Treat Rep. 1981; 65:715-7. [IDIS 137002] [PubMed 6166376]

99. Fuks JZ, Aisner J, Van Echo DA et al. Randomized study of cyclophosphamide, doxorubicin, and etoposide (VP16-213) with or without cisplatinum in non-small cell lung cancer. J Clin Oncol. 1983; 1:295-301. [PubMed 6686849]

100. European Organization for Research on the Treatment of Cancer, Clinical Screening Group. Epipodophyllotoxin VP 16213 in treatment of acute leukaemias, haematosarcomas, and solid tumours. Br Med J. 1973; 3:199-202. [IDIS 37277] [PubMed 4578134]

101. Mathe G, Schwarzenberg L, Pouillart P et al. Two epipodophyllotoxin derivatives, VM 26 and VP 16213, in the treatment of leukemias, hematosarcomas, and lymphomas. Cancer. 1974; 34:985-92. [IDIS 51011] [PubMed 4608026]

102. Jacobs P, Dubovsky D, Hougaard M et al. Epipodophyllotoxin VP 16213 in acute non-lymphoblastic leukaemia. Br Med J. 1975; 1:396. [IDIS 50783] [PubMed 1115948]

103. Cavalli F, Sonntag R, Brunner KW. Epipodophyllotoxin VP 16213 in acute non-lymphoblastic leukaemia. Br Med J. 1975; 4:227. [IDIS 59740] [PubMed 1059494]

104. McKenna RW, Bloomfield CD, Dick F et al. Acute monoblastic leukemia: diagnosis and treatment of ten cases. Blood. 1975; 46:481-94. [PubMed 169929]

105. Smith IE, Gerken ME, Clink HM et al. VP 16-213 in acute myelogenous leukaemia. Postgrad Med J. 1976; 52:66-70. [PubMed 772645]

106. Van Echo DA, Wiernik PH, Aisner J. High-dose VP 16-213 (NSC 141540) for the treatment of patients with previously treated acute leukemia. Cancer Clin Trials. 1980; 3:325-8. [PubMed 6933027]

107. Varini M, Cavalli F. Etoposide in the treatment of acute leukemia in adults. Cancer Treat Rev. 1982; 9(Suppl A):59-62. [IDIS 178610] [PubMed 7127335]

108. Rivera G, Bowman WP, Look AT et al. Single-agent and combination chemotherapy with etoposide in the acute leukemias of childhood. Cancer Treat Rev. 1982; 9(Suppl A):53-7. [IDIS 178609] [PubMed 6181873]

109. Rivera G, Avery T, Pratt C. 4′-Demethylepipodophyllotoxin 9-(4,6-O-thenylidene-β-d-glucopyranoside) (NSC-122819; VM-26) and 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside) (NSC-141540; VP-16-213) in childhood cancer: preliminary observations. Cancer Chemother Rep. 1975; 59(4 Part 1):743-9. [IDIS 58374] [PubMed 1100225]

110. Chard RL Jr, Krivit W, Bleyer WA et al. Phase II study of VP-16-213 in childhood malignant disease: a Children’s Cancer Study Group Report. Cancer Treat Rep. 1979; 63:1755-9. [IDIS 110513] [PubMed 294306]

111. Van Echo DA, Lichtenfeld KM, Wiernik PH. Vinblastine, 5-azacytidine, and VP-16-213 therapy for previously treated patients with acute nonlymphocytic leukemia. Cancer Treat Rep. 1977; 61:1599-602. [IDIS 87615] [PubMed 72605]

112. Look AT, Dahl GV, Kalwinsky D et al. Effective remission induction of refractory childhood acute nonlymphocytic leukemia by VP-16-213 plus azacitidine. Cancer Treat Rep. 1981; 65:995-9. [IDIS 141650] [PubMed 6170431]

113. Getaz EP, Staples WG. Chronic myelomonocytic leukaemia: a case report. S Afr Med J. 1977; 51:852-3. [IDIS 85165] [PubMed 267330]

114. Schiffer CA, DeBellis R, Kasdorf H et al. Treatment of the blast crisis of chronic myelogenous leukemia with 5-azacytidine and VP-16-213. Cancer Treat Rep. 1982; 66:267-71. [IDIS 145466] [PubMed 6173123]

115. Jacobs P, King HS, Sealy GRH. Epipodophyllotoxin (VP 16-213) in the treatment of diffuse histiocytic lymphoma. S Afr Med J. 1975; 49:483-5. [IDIS 53169] [PubMed 167460]

116. Cecil JW, Quagliana JM, Coltman CA et al. Evaluation of VP-16-213 in malignant lymphoma and melanoma. Cancer Treat Rep. 1978; 62:801-3. [IDIS 94751] [PubMed 657164]

117. Jacobs P, King HS, Cassidy F et al. VP-16-213 in the treatment of stage III and IV diffuse lymphocytic lymphoma of the large cell (histiocytic) variety: an interim report. Cancer Treat Rep. 1981; 65:987-93. [IDIS 141649] [PubMed 7028260]

118. Taylor RE, McElwain TJ, Barrett A et al. Etoposide as a single agent in relapsed advanced lymphomas: a phase II study. Cancer Chemother Pharmacol. 1982; 7:175-7. [IDIS 178831] [PubMed 7083459]

119. Nissen NI, Larsen V, Pedersen H et al. Phase I clinical trial of a new antitumor agent, 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside) (NSC-141540; VP-16-213). Cancer Chemother Rep. 1972; 56:769-77. [IDIS 31678] [PubMed 4634038]

120. Bender RA, Anderson T, Fisher RI et al. Activity of the epipodophyllotoxin VP-16 in the treatment of combination chemotherapy-resistant non-Hodgkin lymphoma. Am J Hematol. 1978; 5:203-9. [PubMed 752259]

121. Kroner T, Obrecht JP, Jungi WF et al. Etoposide as single agent and in combination with cis-platinum for malignant lymphomas. Cancer Treat Rev. 1982; 9(Suppl A):39-43. [IDIS 178607] [PubMed 6889920]

122. Hansen MM, Bloomfield CD, Jorgensen J et al. VP-16-213 in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone in the treatment of non-Hodgkin’s lymphomas. Cancer Treat Rep. 1980; 64:1135-7. [IDIS 129031] [PubMed 7459900]

123. von Heyden HW, Scherpe A, Nagel GA. Cis-dichlorodiammineplatinum (II) (cis-platinum) and etoposide for patients with refractory lymphomas. Cancer Treat Rev. 1982; 9(Suppl A):45-52. [IDIS 178608] [PubMed 6889921]

124. Cabanillas F, Hagemeister FB, Bodey GP et al. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood. 1982; 60:693-7. [IDIS 159195] [PubMed 7104493]

125. Cabanillas F, Burgess MA, Bodey GP et al. Sequential chemotherapy and late intensification for malignant lymphomas of aggressive histologic type. Am J Med. 1983; 74:382-8. [IDIS 168014] [PubMed 6187213]

126. Segal ML, Grever MR, Ungerleider J et al. Treatment of refractory non-Hodgkin’s lymphoma (NHL) with ifosfamide (IF) and VP-16 (VP). Proc Am Soc Clin Oncol. 1982; 1:159.

127. Fisher RI, DeVita VT, Hubbard SM et al. Diffuse aggressive lymphomas: increased survival after alternating flexible sequences of ProMACE and MOPP chemotherapy. Ann Intern Med. 1983; 98:304-9. [IDIS 167191] [PubMed 6600902]

128. Thomsen K. Scandinavian Mycosis Fungoides Trial. Cancer Treat Rep. 1979; 63:709-11. [IDIS 112386] [PubMed 445520]

129. Santoro A, Bonfante V, Bonadonna G. Third-line chemotherapy with CCNU, etoposide and prednimustine (CEP) in Hodgkin’s disease (HD) resistant to MOPP and ABVD. Proc Am Soc Clin Oncol. 1982; 1:165.

130. Newlands ES, Bagshawe KD. The role of VP16-213 (etoposide; NSC-141540) in gestational choriocarcinoma. Cancer Chemother Pharmacol. 1982; 7:211-4. [IDIS 178840] [PubMed 7083462]

131. Cavalli F, Rosencweig M, Renard J et al. A phase II study of oral VP-16-213 in patients with hepatocellular carcinoma. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1981; 22:457.

132. Melia WM, Johnson PJ, Williams R. Induction of remission in hepatocellular carcinoma: a comparison of VP 16 with adriamycin. Cancer. 1983; 51:206-10. [IDIS 165065] [PubMed 6295596]

133. Laubenstein LJ, Krigel RL, Odajnyk CM et al. Treatment of epidemic Kaposi’s sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine. J Clin Oncol. 1984; 2:1115-20. [PubMed 6208343]

134. Schell FC, Yap HY, Hortobagyi GN et al. Phase II study of VP16-213 (etoposide) in refractory metastatic breast carcinoma. Cancer Chemother Pharmacol. 1982; 7:223-5. [IDIS 178843] [PubMed 7083463]

135. Lokich J, Corkery J. Phase I study of VP-16-213 (etoposide) administered as a continuous 5-day infusion. Cancer Treat Rep. 1981; 65:887-9. [IDIS 138179] [PubMed 7273024]

136. Aisner J, Van Echo DA, Whitacre M et al. A phase I trial of continuous infusion VP16-213 (etoposide). Cancer Chemother Pharmacol. 1982; 7:157-60. [IDIS 178829] [PubMed 7083457]

137. Cavalli F, Sonntag RW, Ryssel HJ et al. Lack of severe hypotension with VP-16-213 administered directly Iv. Cancer Treat Rep. 1977; 61:1411. [IDIS 95248] [PubMed 589604]

138. Schechter JP, Jones SE, Jackson RA. Myocardial infarction in a 27-year-old woman: possible complication of treatment with VP-16-213 (NSC-141540), mediastinal irradiation, or both. Cancer Chemother Rep. 1975; 59(5 Part 1):887-8. [IDIS 63078] [PubMed 1203893]

139. Phillips NC, Lauper RD. Review of etoposide. Clin Pharm. 1983; 2:112-9. [IDIS 168944] [PubMed 6309469]

140. Sutherland CM, Loutfi A. Unusual reaction to VP-16-213 and avoidance by prolonged infusion. Cancer Treat Rep. 1982; 66:409.

141. Young CW, Ihde DC, Von Stubbe W. Preliminary clinical trial of 4′-demethylepipodophyllotoxin-β-d-ethylidene-glucoside (VP 16-213). Proc Annu Meet Am Assoc Cancer Res. 1973; 14:60.

142. Fontana JA. Radiation recall associated with VP-16-213 therapy. Cancer Treat Rep. 1979; 63:224-5. [IDIS 121081] [PubMed 221115]

143. Dorr RT, Alberts DS. Skin ulceration potential without therapeutic anticancer activity for epipodophyllotoxin commercial diluents. Invest New Drugs. 1983; 1:151-9. [PubMed 6678864]

144. Karp G, Antman K, Canellos G. VP-16-213: a phase II trial using a weekly schedule. Cancer Clin Trials. 1981; 4:465-7. [IDIS 178604] [PubMed 7318129]

145. Jackson DV Jr, Wells HB, White DR et al. Lack of potentiation of vincristine-induced neurotoxicity by VP-16-213. Am J Clin Oncol. 1983; 6:327-30. [IDIS 178815] [PubMed 6303106]

146. Thant M, Hawley RJ, Smith MT et al. Possible enhancement of vincristine neuropathy by VP-16. Cancer. 1982; 49:859-64. [IDIS 146039] [PubMed 6277454]

147. Cavalli F, Hasler E, Ryssel HJ et al. A combination of cyclophosphamide, methotrexate, vincristine, and VP-16-213 in the treatment of bronchogenic carcinoma. Tumori. 1977; 63:169-73. [PubMed 898287]

148. Huang CC, Hou Y, Wang JJ. Effects of a new antitumor agent, epipodophyllotoxin, growth and chromosomes in human hematopoietic cell lines. Cancer Res. 1973; 33:3123-9. [PubMed 4760528]

149. Food and Drug Administration. Prescription drug advertising; content and format for labeling of human prescription drugs. Fed Regist. 1979; 44:37434-67.

150. Schabel FM Jr, Trader MW, Laster WR Jr et al. cis-Dichlorodiammineplatinum(II): combination chemotherapy and cross-resistance studies with tumors of mice. Cancer Treat Rep. 1979; 63:1459-73. [PubMed 291480]

151. Burchenal JH, Kalaher K, Dew K et al. Studies of cross-resistance, synergistic combinations and blocking of activity of platinum derivatives. Biochimie. 1978; 60:961-5.

152. Mabel JA, Little AD. Therapeutic synergism in murine tumors for combinations of cis-diamminedichloroplatinum with VP 16-213 or BCNU. Proc Annu Meet Am Assoc Cancer Res Proc Annu Meet Am Soc Clin Oncol. 1979; 20:230.

153. Dombernowsky P, Nissen NI. Combination chemotherapy with 4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside), VP 16-213 (NSC 141540) in L1210 leukemia. Eur J Cancer. 1976; 12:181-8. [PubMed 939236]

154. Rivera G, Avery T, Roberts D. Response of L1210 to combinations of cytosine arabinoside and VM-26 or VP16-213. Eur J Cancer. 1975; 11:639-47. [PubMed 1220978]

155. Stahelin H. Delayed toxicity of epipodophyllotoxin derivatives (VM 26 and VP 16-213), due to a local effect. Eur J Cancer. 1976; 12:925-31. [PubMed 991901]

156. C.dtdon RW, Sikic BI. Continuous infusion or bolus injection in cancer chemotherapy. Ann Intern Med. 1983; 99:823-33. (IDIS 179203)

157. Hayes FA, Green A, Thompson E et al. Phase II trial of VP16-213 in pediatric solid tumors. Proc Am Assoc Clin Oncol. 1983; 2:66.

158. Wolff SN, Fer MF, McKay CM et al. High-dose VP-16-213 and autologous bone marrow transplantation for refractory malignancies: a phase I study. J Clin Oncol. 1983; 1:701-5. [PubMed 6366131]

159. Keller JH (Bristol Laboratories, Syracuse, NY): Personal communication; 1984 Jun, Jul.

160. Harvey VJ, Slevin ML, Joel SP et al. The pharmacokinetics of oral etoposide (VP16-213). Proc Am Soc Clin Oncol. 1984; 3:24.

161. Pfeffer M, Nardella PA, Van Harken DR et al. The absolute oral bioavailability and pharmacokinetics of etoposide. In: Issell BF, Muggia FM, Carter SK, eds. Etoposide (VP-16): current status and new developments. New York: Academic Press, Inc,; 1984:127-40.

162. Postmus PE, Holthuis JJM, Haaxma-Reiche H et al. Penetration of VP 16-213 into cerebrospinal fluid after high-dose intravenous administration. J Clin Oncol. 1984; 2:215-20. [PubMed 6321690]

163. Perry MC, Moertel CG, Schutt AJ et al. Phase II studies of dianhydrogalactitol and VP-16-213 in colorectal cancer. Cancer Treat Rep. 1976; 60:1247-50. [IDIS 75069] [PubMed 797447]

164. Wolff SN, Johnson DH, Hainsworth JD et al. High-dose VP-16-213 monotherapy for refractory germinal malignancies: a phase II study. J Clin Oncol. 1984; 2:271-4. [PubMed 6368760]

165. Lederman GS, Garnick MB, Canellos GP et al. Chemotherapy of refractory germ cell cancer with etoposide. J Clin Oncol. 1983; 1:706-9. [PubMed 6321675]

166. Johnson DH, Greco FA, Wolff SN. Etoposide-induced hepatic injury: a potential complication of high-dose therapy. Cancer Treat Rep. 1983; 67:1023-4. [IDIS 181590] [PubMed 6315228]

167. Loike JD, Brewer CF, Sternlicht H et al. Structure-activity study of the inhibition of microtubule assembly in vitro by podophyllotoxin and its congeners. Cancer Res. 1978; 38:2688-93. [PubMed 679171]

168. Brewer CF, Loike JD, Horwitz SB. Conformational analysis of podophyllotoxin and its congeners. Structure-activity relationship in microtubule assembly. J Med Chem. 1979; 22:215-21. [PubMed 423203]

169. Kalwinsky DK, Look AT, Ducore J et al. Effects of the epipodophyllotoxin VP-16-213 on cell cycle traverse, DNA synthesis, and DNA strand size in cultures of human leukemic lymphoblasts. Cancer Res. 1983; 43:1592-7. [PubMed 6572554]

170. Long BH, Minocha A. Inhibition of topoisomerase II by VP-16-213 (etoposide), VM-26 (teniposide), and structural congeners as an explanation for in vivo DNA breakage and cytotoxicity. Proc Annu Meet Am Soc Clin Oncol. 1983; 24:321.

171. Long BH, Musial ST, Butwell T et al. Comparison of DNA breakage produced by VP16-213 and VM26 and repair in sensitive and resistant human lung carcinoma cell lines. Proc Annu Meet Am Soc Clin Oncol. 1984; 25:333.

172. Glisson BS, Ross WE. Characterization of VP-16 induced DNA damage in isolated L1210 nuclei. Proc Annu Meet Am Soc Clin Oncol. 1984; 25:299.

173. Ho DHW, Kanellopoulos KA, Yap HY et al. Clinical pharmacology of etoposide by radioimmunoassay. Proc Annu Meet Am Soc Clin Oncol. 1983; 24:131.

174. Colombo T, D’Incalci M, Farina P et al. Comparison of pharmacokinetics of VP16 in mice, rats and humans. Proc Annu Meet Am Soc Clin Oncol. 1983; 24:292.

175. Stewart DJ, Richard M, Hugenholtz H et al. VP-16 (VP) and VM-26 (VM) penetration into human brain tumors (BT). Proc Annu Meet Am Soc Clin Oncol. 1983; 24:133.

176. Sinkule JA, Hutson P, Hayes FA et al. Pharmacokinetics of etoposide (VP16) in children and adolescents with refractory solid tumors. Cancer Res. 1984; 44:3109-13. [IDIS 187012] [PubMed 6539169]

177. Dow LW, Sinkule JA, Look AT et al. Comparative cytotoxic and cytokinetic effects of the epipodophyllotoxins 4′- demethylepipodophyllotoxin-9- (4,6-O-2-ethylidene-β-d-glucopyranoside) and 4′- demethylepipodophyllotoxin-9- (4,6-O-2-thenylidene-β-d-glucopyranoside) and their metabolites on human leukemic lymphoblasts. Cancer Res. 1983; 43:5699-706. [PubMed 6580063]

178. O’Dwyer PJ, Weiss RB, Fortner C et al. Hypersensitivity reactions induced by etoposide. Proc Am Soc Clin Oncol. 1984; 3:35.

179. Giever RJ, Heusinkveld RS, Manning MR et al. Enhanced radiation reaction following combination chemotherapy for small cell carcinoma of the lung, possibly secondary to VP16-213. Int J Radiat Oncol Biol Phys. 1982; 8:921-3. [PubMed 6286559]

180. Reviewers’ comments (personal observations).

181. Sieber SM, Whang-Peng J, Botkin C et al. Teratogenic and cytogenetic effects of some plant-derived antitumor agents (vincristine, colchicine, maytansine, VP-16-213 and VM-26) in mice. Teratology. 1978; 18:31-48. [PubMed 694777]

182. Bosl GJ, Yagoda A, Golbey RB et al. Role of etoposide-based chemotherapy in the treatment of patients with refractory or relapsing germ cell tumors. Am J Med. 1985; 78:423-8. [IDIS 197655] [PubMed 2983547]

183. Evans WK, Osoba D, Feld R et al. Etoposide (VP-16) and cisplatin: an effective treatment for relapse in small-cell lung cancer. J Clin Oncol. 1985; 3:65-71. [PubMed 2981293]

184. Crawford J, Ozer H, Stoller R et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med. 1991; 325:164-70. [IDIS 282870] [PubMed 1711156]

185. Wong LC, Choo YC, Ma HK. Use of oral VP16-213 as primary chemotherapeutic agent in treatment of gestational trophoblastic disease. Am J Obstet Gynecol. 1984; 150:924-7. [IDIS 194007] [PubMed 6095666]

186. Smith EB, Clarke-Pearson DL, Creasman WT. A VP16-213- and cisplatin-containing regimen for treatment of refractory ovarian germ cell malignancies. Am J Obstet Gynecol. 1984; 150:927-31. [IDIS 194008] [PubMed 6542313]

187. Lauper RD (Bristol-Myers Oncology, Syracuse, NY): Personal communication; 1985 Nov.

188. Bristol Laboratories. VePesid prescribing information. Syracuse, NY; 1986 Sep.

189. Bristol Laboratories. VePesid (etoposide) for injection and oral capsules prescribing information. Princeton, NJ; 1995 Jun.

190. Bristol Laboratories. VePesid (etoposide, VP-16) capsules: clinical profile in lung cancer. Publication N-W56. Evansville, IN; 1987 May.

191. Smyth RD, Pfeffer M, Scalzo A et al. Bioavailability and pharmacokinetics of etoposide (VP-16). Semin Oncol. 1985; 12(1 Suppl 2):48-51. [PubMed 3975657]

192. Stewart DJ, Nundy D, Maroun JA et al. Bioavailability, pharmacokinetics, and clinical effects of an oral preparation of etoposide. Cancer Treat Rep. 1985; 69:269-73. [IDIS 198391] [PubMed 3884152]

193. Harvey VJ, Slevin ML, Joel SP et al. The pharmacokinetics of VP-16 (etoposide) and bioavailability following different methods of administration. Br J Clin Pharmacol. 1984; 17:204-5P.

194. Harvey VJ, Slevin ML, Joel SP et al. The effect of dose on the bioavailability of oral etoposide. Cancer Chemother Pharmacol. 1986; 16:178-81. [PubMed 3004772]

195. Harvey VJ, Slevin ML, Joel SP et al. Variable bioavailability following repeated oral doses of etoposide. Eur J Cancer Clin Oncol. 1985; 21:1315-9. [PubMed 3000790]

196. Harvey VJ, Slevin ML, Joel SP et al. The effect of food and concurrent chemotherapy on the bioavailability of oral etoposide. Br J Cancer. 1985; 52:363-7. [PubMed 2994705]

197. Clark PI, Slevin ML. The clinical pharmacology of etoposide and teniposide. Clin Pharmacokinet. 1987; 12:223-52. [IDIS 229317] [PubMed 3297462]

198. Williams SD, Birch R, Einhorn LH et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987; 316:1435-40. [IDIS 231286] [PubMed 2437455]

199. Comis RL. Clinical trials of cyclophosphamide, etoposide, and vincristine in the treatment of small-cell lung cancer. Semin Oncol. 1986; 13(3 Suppl 3):40-4. [PubMed 3020699]

200. Comis R, Lawson R, Maroun J et al. Cytoxan (C), etoposide (E), vincristine (V) versus Cytoxan, Adriamycin (A), vincristine versus Cytoxan, vincristine in the treatment of small cell lung cancer (SCLC). Proc Am Soc Clin Oncol. 1987; 6:168.

201. Comis RL. Oral etoposide in small-cell lung cancer. Semin Oncol. 1986; 13(3 Suppl 3):75-8. [PubMed 3020704]

202. Hirsch FR, Hansen HH, Hansen M et al. The superiority of combination chemotherapy including etoposide based on in vivo cell cycle analysis in the treatment of extensive small-cell lung cancer: a randomized trial of 288 consecutive patients. J Clin Oncol. 1987; 5:585-91. [PubMed 3031225]

203. Evans WK, Feld R, Murray N et al. Superiority of alternating non-cross-resistant chemotherapy in extensive small cell lung cancer: a multicenter, randomized clinical trial by the National Cancer Institute of Canada. Ann Intern Med. 1987; 107:451-8. [IDIS 234484] [PubMed 2820289]

204. Splinter T, Kok T, Kho S et al. A multicenter phase II trial of cisplatin and oral etoposide (VP-16) in inoperable non-small-cell lung cancer. Semin Oncol. 1986; 13(3 Suppl 3):97-103. [PubMed 3020707]

205. Cullen MH, Latief TN, Spooner D et al. Cisplatin, etoposide, and radiotherapy in regional inoperable squamous cell carcinoma of the bronchus. Semin Oncol. 1985; 12(1 Suppl 2):14-6. [PubMed 4038819]

206. Testicular cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Library of Medicine; 1993 Oct 1.

207. Ozols RF, Yagoda A. Genitourinary cancer. In: Pinedo HM, Longo DL, Chabner BA, eds. Cancer chemotherapy and biologic response modifiers. Annual 9. New York: Elsevier Science Publishers B.V. (Biomedical Division); 1987:280-302.

208. Ozola RF, Yagoda A. Genitourinary cancer. In: Pinedo HM, Longo DL, Chabner BA, eds. Cancer chemotherapy and biological response modifiers. Annual 10. New York: Elsevier Science Publishers B.V. (Biomedical Division); 1988:271-90.

209. Bergmann KA. Current concepts in clinical therapeutics: Testicular cancer. Clin Pharm. 1987; 6:693-706. [IDIS 233555] [PubMed 2445518]

210. Priest ER, Vogelzang NJ. Optimal drug therapy in the treatment of testicular cancer. Drugs. 1991; 42:52-64. [PubMed 1718685]

211. Oncolytic drugs: principles of cancer chemotherapy. In: Drug evaluations subscription. Chicago, IL; American Medical Association, III/ONC-1:27, Summer 1993.

212. Loehrer PJ, Williams SD, Einhorn LH. Testicular cancer: the quest continues. J Natl Cancer Inst. 1988; 80:1373-83. [PubMed 3050140]

213. Pizzocaro G, Piva L, Salvioni R et al. Cisplatin, etoposide, bleomycin first-line therapy and early resection of residual tumor in far-advanced germinal testis cancer. Cancer. 1985; 56:2411-15. [IDIS 209508] [PubMed 2412683]

214. Loehrer PJ, Birch R, Williams SD et al. Chemotherapy of metastatic seminoma; the Southeastern Cancer Study Group experience. J Clin Oncol. 1987; 5:1212-20. [PubMed 2442317]

215. Anon. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther. 2000; 42:83-92. [PubMed 10994034]

216. American Academy of Pediatrics Committee on Fetus and Newborn and Committee on Drugs. Benzyl alcohol: toxic agent in neonatal units. Pediatrics. 1983; 72:356-8. [IDIS 175725] [PubMed 6889041]

217. Anon. Benzyl alcohol may be toxic to newborns. FDA Drug Bull. 1982; 12(2):10-11. [PubMed 7188569]

218. Centers for Disease Control. Neonatal deaths associated with use of benzyl alcohol. MMWR Morb Mortal Wkly Rep. 1982; 31:290-1. [IDIS 150868] [PubMed 6810084]

219. Gershanik J, Boecler B, Ensley H et al. The gasping syndrome and benzyl alcohol poisoning. N Engl J Med. 1982; 307:1384-8. [IDIS 160823] [PubMed 7133084]

220. Menon PA, Thach BT, Smith CH et al. Benzyl alcohol toxicity in a neonatal intensive care unit: incidence, symptomatology, and mortality. Am J Perinatol. 1984; 1:288-92. [PubMed 6440575]

221. Anderson CW, Ng KJ, Andresen B et al. Benzyl alcohol poisoning in a premature newborn infant. Am J Obstet Gynecol. 1984; 148:344-6. [IDIS 181207] [PubMed 6695984]

222. Klastersky J, Sculier JP, Lacroix H et al. A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small cell lung cancer. European Organization for Research and Treatment of Cancer protocol 07861. J Clin Oncol. 1990; 8:1556-62. [PubMed 2167953]

223. Testicular cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Aug 1.

224. Bajorin DF, Sarosdy MF, Pfister DG et al. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol. 1993; 11:598-606. [PubMed 8386751]

225. Horwich A, Dearnaley DP, Nicholls J et al. Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors. J Clin Oncol. 1991; 9:62-9. [PubMed 1702147]

226. Neuroblastoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Aug 1.

227. Philip T, Gentet JC, Carrie C et al. Phase II studies of combinations of drugs with high-dose carboplatin in neuroblastoma (800 mg/m2 to 1 g 250/m2): a report from the LMCE group. Prog Clin Biolog Res. 1988; 271:573-82.

228. Frappaz D, Michon J, Hartmann O et al. Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study. J Clin Oncol. 1992; 10:1592-601. [PubMed 1403039]

229. Broun ER, Nichols CR, Kneebone P et al. Long-term outcome of patients with relapsed and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. Ann Int Med. 1992; 117:124-8. [IDIS 299035] [PubMed 1318648]

230. Motzer RJ, Bosl GJ. High-dose chemotherapy for resistant germ cell tumors: recent advances and future directions. J Natl Cancer Inst. 1992; 84:1703-9. [PubMed 1331482]

231. Wilms’ tumor. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 1995 Aug 1.

232. Pein F, Tournade M, Zucker J et al. Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms’ tumor—a phase II study by the French Society of Pediatric Oncology. J Clin Oncol. 1994; 12:931-6. [IDIS 330528] [PubMed 8164044]

233. Bosl GJ, Bajorin DF. Etoposide plus carboplatin or cisplatin in good-risk patients with germ cell tumors: a randomized comparison. Semin Oncol. 1994; 21(Suppl 12):61-4. [PubMed 7992068]

234. Marina NM, Wilimas JA, Meyer WH et al. Refining therapeutic strategies for patients with resistant Wilms’ tumor. Am J Pediatr Hematol/Oncol. 1994; 16:296-300.

235. de Camargo B, Melaragno R, Saba e Silva N et al. Phase II study of carboplatin as a single drug for relapsed Wilms’ tumor: experience of the Brazilian Wilms’ Tumor Study Group. Med Pediatr Oncol. 1994; 22:258-60. [PubMed 8107657]

236. Langer CJ, Leighton JC, Comis RL et al. Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer: a phase II toxicity, response, and survival analysis. J Clin Oncol. 1995; 13:1860-70. [IDIS 351040] [PubMed 7543559]

237. Non-small cell lung cancer. From PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

238. Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 ramdomised clinical trials. BMJ. 1995; 311:899-909. [PubMed 7580546]

239. Reviewers’ comments (personal observations) on carboplatin 10:00.

240. Chazard M, Boutan-Laruze A. High failure rate of carboplatin-etoposide combination in good risk non-seminomatous germ cell tumours. Eur J Cancer. 1993; 29A:1504-9. [PubMed 8217352]

241. Mead Johnson. Ifex (sterile ifosfamide) product information. Princeton, NJ; 1992 Dec.

242. Schoenike SE, Dana WJ. Ifosfamide and mesna. Clin Pharm. 1990; 9:179-91. [IDIS 264394] [PubMed 2107997]

243. Dechant KL, Brogden RN, Pilkington T et al. Ifosfamide/mesna: a review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer. Drugs. 1991; 42:428-67. [PubMed 1720382]

244. Loehrer PJ, Lauer R, Roth BJ et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Int Med. 1988; 109:540-6. [IDIS 246234] [PubMed 2844110]

245. Motzer RJ, Cooper K, Geller NL et al. The role of ifosfamide plus cisplatin-based chemotherapy as salvage therapy for patients with refractory germ cell tumors. Cancer. 1990; 66:2476-81. [IDIS 275597] [PubMed 2174300]

246. Ghosn M, Droz JP, Theodore C et al. Salvage chemotherapy in refractory germ cell tumors with etoposide (VP-16) plus ifosfamide plus high-dose cisplatin. Cancer. 1988; 62:24-7. [IDIS 244194] [PubMed 3133101]

247. Reviewers’ comments (personal observations) on ifosfamide 10:00.

248. Mead Johnson, Princeton, NJ: Personal communication on ifosfamide 10:00.

249. Loehrerr PJ, Rynard S, Ansari R et al. Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer. Cancer. 1992; 69:669-73. [IDIS 291929] [PubMed 1309677]

250. Ettinger DS. The place of ifosfamide in chemotherapy of small cell lung cancer: the Eastern Cooperative Oncology Group Experience and a selected literature update. Semin Oncol. 1995; 22(Suppl 2):23-7. [PubMed 7846538]

251. Skarlos DV, Samantas E, Kosmidis P et al. Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer. Ann Oncol. 1992; 5:601-7.

252. Wagstaff AJ, Ward A, Benfield P et al. Carboplatin: a preliminary review of its pharmacodynamic properties and therapeutic efficacy in the treatment of cancer. Drugs. 1989; 37:162-90. [IDIS 251676] [PubMed 2649354]

253. Small cell lung cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

254. Smith IE, Perren TJ, Ashley SA et al. Carboplatin, etoposide and ifosfamide as intensive chemotherapy for small-cell lung cancer. J Clin Oncol. 1990; 8:899-905. [PubMed 2159056]

255. Thatcher N, Lind M, Stout R et al. Carboplatin, ifosfamide and etoposide with mid-course vincristine and thoracic radiotherapy for “limited” stage small cell carcinoma of the bronchus. Br J Cancer. 1989; 60:98-101. [PubMed 2553090]

256. Bristol-Myers Squibb. Etopophos (etoposide phosphate) for injection prescribing information. Princeton, NJ; 1997 Dec.

257. Shields PG, Dawkins F, Holmlund J et al. Low-dose multidrug chemotherapy plus pneumocystis carinii pneumonia prophylaxis for HIV-related Kaposi’s sarcoma. J Acquir Immune Defic Syndr. 1990; 3:695-700. [PubMed 1693677]

258. Kaposi’s sarcoma. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Apr.

259. Northfelt DW. Treatment of Kaposi’s sarcoma: current guidelines and future perspectives. Drugs. 1994; 48:569-82. [PubMed 7528130]

260. Gill PS, Rarick M, McCutchan JA et al. Systemic treatment of AIDS-related Kaposi’s sarcoma: results of a randomized trial. Am J Med. 1991; 90:427-33. [IDIS 280110] [PubMed 1707230]

261. De Wit R, Schattenkerk JKME, Boucher CAB et al. Clinical and virological effects of high-dose recombinant interferon-α in disseminated AIDS-related Kaposi’s sarcoma. Lancet. 1988; 2:1214-7. [IDIS 248228] [PubMed 2903953]

262. Groopman JE, Gottlieb MS, Goodman J et al. Recombinant alpha-2 interferon therapy for Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome. Ann Intern Med. 1984; 100:671-6. [IDIS 184370] [PubMed 6712031]

263. Mayer-da-Silva A, Stadler R, Imcke E et al. Disseminated Kaposi’s sarcoma in AIDS: histogenesis-related populations and influence of long-term treatment with rIFN-αA. J Invest Dermatol. 1987; 89:618-24. [PubMed 3680987]

264. Groopman JE. Biology and therapy of epidemic Kaposi’s sarcoma. Cancer. 1987; 59:633-7. [IDIS 225544] [PubMed 10822462]

265. Volberding PA, Mitsuyasu R. Recombinant interferon alpha in the treatment of acquired immune deficiency syndrome—related Kaposi’s sarcoma. Semin Oncol. 1985; 12:2-6. [PubMed 3909416]

266. Mitsuyasu RT, Taylor JMG, Glaspy J et al. Heterogeneity of epidemic Kaposi’s sarcoma: implications for therapy. Cancer. 1986; 57:1657-61. [IDIS 213809] [PubMed 3081246]

267. Safai B. Pathophysiology and epidemiology of epidemic Kaposi’s sarcoma. Semin Oncol. 1987; 14(Suppl 3):7-12. [PubMed 3299718]

268. Krown SE. The role of interferon in the therapy of epidemic Kaposi’s sarcoma. Semin Oncol. 1987; 14(Suppl 3):27-33. [PubMed 2440110]

269. Gelmann EP, Preble OT, Steis R et al. Human lymphoblastoid interferon treatment of Kaposi’s sarcoma in the acquired immune deficiency syndrome: clinical response and prognostic parameters. Am J Med. 1985; 78:737-41. [IDIS 199774] [PubMed 3838854]

270. Kovacs JA, Deyton L, Davey R et al. Combined zidovudine and interferon-α therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1989; 111:280-7. [IDIS 257910] [PubMed 2757312]

271. Krown SE, Real FX, Vadhan-Raj S et al. Kaposi’s sarcoma and the acquired immune deficiency syndrome: treatment with recombinant interferon alpha and analysis of prognostic factors. Cancer. 1986; 57:1662-5. [IDIS 213810] [PubMed 3081247]

272. Krown SE, Gold JWM, Niedzwiecki D et al. Interferon-α with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990; 112:812-21. [IDIS 266655] [PubMed 1971504]

273. Karp JE, Groopman JE, Broder S. Cancer in AIDS. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and practice of oncology. 4th ed. Philadelphia, PA: J.B. Lippincott; 1993:2093-2110.

274. Anon. Treatment of AIDS-related Kaposi’s sarcoma. Am J Hosp Pharm. 1989; 46:1211.

275. Northfelt DW. Efficacy of Doxil (doxorubicin HCl liposome injection) in the treatment of refractory AIDS-related Kaposi’s sarcoma. In: Doxil Clinical Series. Vol. 1, No. 3. Menlo Park, CA: Sequus Pharmaceuticals, Inc; 1996:1-8.

276. Dezube BJ. Safety assessment: Doxil (doxorubicin HCl liposome injection) in refractory AIDS-related Kaposi’s sarcoma. In: Doxil Clinical Series. Vol. 1, No. 2. Menlo Park, CA: Sequus Pharmaceuticals, Inc; 1996:1-8.

277. Alza Pharmaceuticals, Inc. Doxil (doxorubicin HCl liposome injection) prescribing information. Palo Alto, CA; 1999 Jul.

278. Epstein JB, Lozada-Nur F, McLeod WA et al. Oral Kaposi’s sarcoma in acquired immunodeficiency syndrome: review of management and report of the efficacy of intralesional vinblastine. Cancer. 1989; 64:2424-30. [IDIS 261866] [PubMed 2819653]

279. Reviewers’ comments (personal observations) on interferon.

280. Coleman R. Treatment of refractory AIDS-related Kaposi’s sarcoma with Doxil(doxorubicin HCl liposome injection): a pharmacy perspective. In: Doxil Clinical Series. Vol. 1, No. 4. Menlo Park, CA: Sequus Pharmaceuticals, Inc; 1996:1-12.

281. Sequus Pharmaceuticals, Menlo Park, CA: Personal communication.

282. Stewart S, Jablonowski H, Goebel FD et al, and the Doxil trials groups. Randomized comparative trial of Doxil vs bleomycin and vincristine in treatment of AIDS-related KS. In: XI International Conference on AIDS, 1996. Vancouver, BC; 1996 Jul 7–12. Abstract No. LB.B.6026.

283. Northfelt DW, Dezube B, Miller B et al. Randomized comparative trial of Doxil vs. Adriamycin, bleomycin, and vincristine (ABV) in the treatment of severe AIDS-related Kaposi’s sarcoma (AIDS-KS). Blood. 1995; 86(Suppl 1):382.

284. Bogner JR, Kronawitter U, Rolinski B et al. Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma. J Acquir Immune Defic Syndr. 1994; 7:463-8. [IDIS 328948] [PubMed 8158540]

285. Esser S, Bleil M, Reimann G et al. Long term treatment with liposomal doxorubicin in patients with AIDS-related Kaposi’s sarcoma. In: XI International Conference on AIDS, 1996. Vancouver, BC; 1996 Jul 7–12. Abstract No. Th.A.4077.

286. Northfelt DW, Martin FJ, Working P et al. Doxorubicin encapsulated inliposomes containing surface-bound polyethylene glycol: pharmacokinetics, tumor localization, and safety in patients with AIDS-related Kaposi’s sarcoma. J Clin Pharmacol. 1996; 36:55-63. [IDIS 360878] [PubMed 8932544]

287. Gruenaug M, Bogner JR, Loch O et al. Liposomal doxorubicin in pulmonary Kaposi’s sarcoma: improved survival as compared to patients without liposomal doxorubicin. In: XI International Conference on AIDS, 1996: Abstracts-on-disk. Vancouver, BC; 1996 Jul 7–12. Abstract No. Tu.B.2221.

288. Harrison M, Tomlinson D, Stewart S. Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1995; 13:914-20. [IDIS 344867] [PubMed 7707119]

289. Moran TA. Treatment of refractory AIDS-related Kaposi’s sarcoma with Doxil(doxorubicin HCl liposome injection): a nursing perspective. In: Doxil Clinical Series. Vol. 1, No. 5. Menlo Park, CA: Sequus Pharmaceuticals, Inc; 1996:1-8.

290. Abrams DI, Volberding PA. Alpha interferon therapy of AIDS-associated Kaposi’s sarcoma. Semin Oncol. 1986; XIII(Suppl 2):43-7.

291. NeXstar Pharmaceuticals, Inc. DaunoXome (daunorubicin citrate liposome injection) prescribing information. San Dimas, CA; 1999 Apr.

292. Presant CA, Scolaro M, Kennedy P et al. Liposomal daunorubicin treatment of HIV-associated Kaposi’s sarcoma. Lancet. 1993; 341:1242-3. [IDIS 314333] [PubMed 8098393]

293. Gill PS, Wernz J, Scadden DT et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1996; 14:2353-64. [IDIS 371434] [PubMed 8708728]

294. Schurmann D, Dormann A, Grunewald T et al. Successful treatment of AIDS-related pulmonary Kaposi’s sarcoma with liposomal daunorubicin. Eur Respir J. 1994; 7:824-5. [PubMed 8005268]

295. Gill PS, Rarick MU, Espina B et al. Advanced acquired immune deficiency syndrome-related Kaposi’s sarcoma: results of pilot studies using combination chemotherapy. Cancer. 1990; 65:1074-78. [IDIS 263349] [PubMed 1689209]

296. Bristol Laboratories. Etopophos (etoposide phosphate) for injection formulary guide. Princeton, NJ; 1996 Sep.

297. Souhami RL, Spiro SG, Rudd RM et al. Five-day oral etoposide treatment for advanced small-cell lung cancer: randomized comparison with intravenous chemotherapy. J Natl Cancer Inst. 1997; 89:577-80. [IDIS 385512] [PubMed 9106647]

298. Ihde DC. Chemotherapy of lung cancer. N Engl J Med. 1992; 327:1434-41. [IDIS 304946] [PubMed 1328881]

299. Bunn PA Jr, Carney DN. Overview of chemotherapy for small cell lung cancer. Semin Oncol. 1997; 24(Suppl 7):S69-74. [PubMed 9194484]

300. Pignon JP, Arriagada R, Ihde DC et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1992; 327:16-8-24.

301. Bonomi P, Kim K, Fairclough D et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2000; 18:623-31. [IDIS 442904] [PubMed 10653877]

302. Ramanathan RK, Belani CP. Chemotherapy for advanced non-small cell lung cancer: past, present, and future. Semin Oncol. 1997; 24:440-54. [PubMed 9280224]

303. Belani CP, Natale RB, Lee JS et al. Randomized phase III trial comparing cisplatin/etoposide versus carboplatin/paclitaxel in advanced and metastatic non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol. 1998; 17:A1751.

304. Medical Research Council Lung Cancer Working Party. Comparison of oral etoposide and standard intravenous multidrug chemotherapy for small-cell lung cancer: a stopped multicentre randomised trial. Lancet. 1996; 348:563-6. [IDIS 371551] [PubMed 8774567]

305. Miles SA, Mitsuyasu RI, Aboulafia DM. AIDS-related malignancies. In: DeVita VT Jr, Hellman S, Rosenberg SA eds. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1997:2445-67.

306. Ligand Pharmaceuticals, Inc. Panretin (alitretinoin) gel prescribing information. San Diego, CA; 1999 Jan.

307. Stewart S, Jablonowski H, Goebel FD et al. Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1998; 16:683-91. [IDIS 401192] [PubMed 9469358]

308. Northfelt DW, Dezube BJ, Thommes JA et al. Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi’s sarcoma: results of a randomized phase III clinical trial. J Clin Oncol. 1998; 16:2445-51. [IDIS 410501] [PubMed 9667262]

309. Gill PS, Wernz J, Scadden DT et al. Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi’s sarcoma. J Clin Oncol. 1996; 14:2353-64. [IDIS 371434] [PubMed 8708728]

310. Krigel RL, Slywotzky CM, Lonberg M et al. Treatment of epidemic Kaposi’s sarcoma with a combination of interferon-alfa 2b and etoposide. J Biol Response Mod. 1988; 7:359-64. [IDIS 252980] [PubMed 3049944]

311. Lonberg M, Odajnyk C, Krigel R et al. Sequential and simultaneous alpha 2 interferon (IFN) and VP16 in epidemic Kaposi’s sarcoma (EKS). Proc Am Soc Clin Oncol. 1985; 4:2.

312. Markman M, Hakes T, Reichman B et al. Phase 2 trial of chronic low-dose oral etoposide as salvage therapy of platinum-refractory ovarian cancer. J Cancer Res Clin Oncol. 1992; 119:55-7. [PubMed 1400568]

313. Hoskins PJ, Swenerton KD. Oral etoposide is active against platinum-resistant epithelial ovarian cancer. J Clin Oncol. 1994; 12:60-3. [IDIS 324690] [PubMed 8270985]

314. Seymour MT, Mansi JL, Gallagher CJ et al. Protracted oral etoposide in epithelial ovarian cancer: a phase II study in patients with relapsed or platinum-resistant disease. Br J Cancer. 1994; 69:191-5. [PubMed 8286205]

315. Rose PG, Blessing JA, Mayer AR et al. Prolonged oral etoposide as second-line therapy for platinum-resistant and platinum-sensitive ovarian carcinoma: a Gynecologic Oncology Group study. J Clin Oncol. 1998; 16:405-10. [IDIS 401170] [PubMed 9469322]

316. Ovarian epithelial cancer. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Oct.

317. Ovarian germ cell tumor. From: PDQ. Physician data query (database). Bethesda, MD: National Cancer Institute; 2000 Aug.

a. Anon. Drugs of choice for cancer. Treatment Guidelines from Med Lett.. 2003; 1:41-52.

b. AHFS drug information 2004. McEvoy GK, ed. Etoposide. Bethesda, MD: American Society of Health-System Pharmacists; 2004:985-92.

c. Bristol Laboratories. VePesid (etoposide) for injection and capsules prescribing information. Princeton, NJ; 1998 Sep.

d. Bristol Laboratories. Etopophos (etoposide phosphate) for injection prescribing information. Princeton, NJ; 1999 Feb.

HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:465-74.

f. Bristol Laboratories. Etopophos (etoposide phosphate) for injection prescribing information. Princeton, NJ; 2004 Feb.

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