Etoposide (Systemic)


VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): Etopophos; Toposar; VePesid.

Another commonly used name is
VP-16 .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antineoplastic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Tumors, germ cell, testicular (treatment)—Etoposide injection is indicated, in combination with other antineoplastics, for first-line treatment of testicular tumors {18} {20} {82} {83} {84} {85} {86} {87} {88} {89} {90} {91} {92} {93} {94} {95} {96} {97} {98} {99} {100} {101}(Evidence rating: IA).

Carcinoma, lung, small cell (treatment)—Etoposide is indicated in combination with other agents as first-line treatment of small cell lung carcinoma {01}.

[Lymphomas, Hodgkin's (treatment) ]1
[Lymphomas, non-Hodgkin's (treatment)]or
[Leukemia, acute nonlymphocytic (treatment) ]1—Etoposide also is indicated, alone and in combination with other agents, for treatment of Hodgkin's and non-Hodgkin's lymphomas and acute nonlymphocytic (myelocytic) leukemia.

[Ewing's sarcoma (treatment)]1or
[Kaposi's sarcoma, autoimmune deficiency syndrome (AIDS)–associated (treatment)]1—Etoposide is indicated for treatment of Ewing's sarcoma and AIDS-associated Kaposi's sarcoma {03}.

[Carcinoma, adrenocortical (treatment) ]1
[Carcinoma, gastric (treatment)]1
[Hepatoblastoma (treatment)]1
[Leukemia, acute lymphocytic (treatment) ]1
[Lymphomas, cutaneous T-cell (treatment) ]1
[Multiple myeloma (treatment)]1
[Neuroblastoma (treatment)]1
[Sarcomas, soft tissue (treatment) ]1
[Tumors, brain, primary (treatment) ]1 or
[Tumors, trophoblastic, gestational (treatment)]1—Etoposide is indicated, alone or in combination with other agents, for treatment of adrenocortical carcinoma {10} {12} {16}, gastric carcinoma {24} {12} {16}, hepatoblastoma {15} {16}, acute lymphocytic leukemia {10} {12} {16}, cutaneous T-cell lymphomas {02} {16}, multiple myeloma {12} {13} {16}, neuroblastoma {14} {15} {16}, soft tissue sarcomas {12} {16}, primary brain tumors {04} {12} {16}, and gestational trophoblastic tumors {11} {12} {16}.

[Carcinoma, lung, non–small cell (treatment) ]—Etoposide is indicated, alone or in combination with other agents, for treatment of non–small cell lung carcinoma {19}.

[Carcinoma, endometrial (treatment) ]1—Etoposide is considered reasonable medical therapy at some point in the management of endometrial carcinoma {31} {32} {33} {34} {35}(Evidence rating: IIID).

[Carcinoma, unknown primary site (treatment )]1—Etoposide is indicated for the first-line treatment of carcinoma of unknown primary site (CUPS), as part of a combination regimen with paclitaxel and carboplatin. There was not a clear consensus by the USP medical experts. Some of the experts are hesitant about the use of this regimen and suggest that individual case factors (e.g. metastatic sites, disease factors, patient characteristics, etc.) be considered when choosing an appropriate treatment.{114}{115}{116}{117}{118}{119}

[Retinoblastoma (treatment)]1
[Thymoma (treatment)]1 or
[Wilms' tumor (treatment)]1—Etoposide is considered reasonable medical therapy at some point in the management of retinoblastoma {36} {37} {38} {39} {40} {41} {42} {43} {44} {45} {46} {47}(Evidence rating: IIID), thymoma {26} {27} {28} {29} {30}(Evidence rating: IIID), and Wilms' tumor {48} {49} {50} {51} {52} {53} {54} {55} {56} {57} {58} {59} {60} {61} {62} {63}(Evidence rating: IIID).

[Osteosarcoma (treatment)]1—Etoposide is considered reasonable medical therapy at some point in the management of osteosarcoma {64} {65} {66} {67} {68}(Evidence rating: IIID).

[Tumors, germ cell, ovarian (treatment) ]1—Etoposide is indicated, in combination with other antineoplastics, for first-line treatment of ovarian germ cell tumors {69} {70} {71} {72} {73} {74} {75} {76} {77} {78} {79} {80} {81}(Evidence rating: IIID).

Acceptance not established
Use of etoposide for the treatment of hormone-refractory prostate cancer has not been established.{103}{104}{105}{106}{107}{108}{109}{110}{111}{112}{113}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Etoposide: 588.57 {25}
    Etoposide phosphate: 668.55 {25}


Other characteristics
    Etoposide: Lipophilic.

Mechanism of action/Effect:

The exact mechanism of etoposide's antineoplastic effect is unknown. Etoposide is a topoisomerase II inhibitor {06}. It seems to act at the premitotic stage of cell division to inhibit DNA synthesis; it is cell cycle–dependent and phase-specific, with maximum effect on the S and G 2 phases of cell division.

Absorption:

Variable, dose-dependent oral bioavailability; absorption decreases as the dose of etoposide increases {21}; mean 50% (range, 25 to 75%) {01}.

Distribution:

Low and variable into cerebrospinal fluid (CSF). Concentrations are higher in normal lung than in lung metastases, and are similar in primary tumors and normal tissues of the myometrium {01}.

Protein binding:

Very high (97%) in vitro {01}. Etoposide binding ratio correlates directly with serum albumin in healthy individuals and cancer patients {01}. The unbound fraction has been found to correlate significantly with bilirubin in a group of cancer patients {01}. Phenylbutazone, sodium salicylate, and aspirin displace protein-bound etoposide in vitro {01}.

Biotransformation:

Hepatic {01}.

Half-life:

Terminal (biphasic)—7 hours (range, 3 to 12).

Elimination:
    Renal—44 to 60% (67% of that unchanged).
    Fecal—Up to 16% (as unchanged drug and metabolites).
    Biliary—6% or less {01}.


Precautions to Consider

Carcinogenicity

Secondary malignancies are potential delayed effects of many antineoplastic agents, although it is not clear whether the effect is related to their mutagenic or immunosuppressive action. The effects of dose and duration of therapy are also unknown, although risk seems to increase with long-term use. Although information is limited, available data seem to indicate that the carcinogenic risk is greatest with the alkylating agents.

Acute leukemia (onset 2 to 3 years) has been reported in patients treated with topoisomerase II inhibitors such as etoposide {01} {22}.

Mutagenicity

Etoposide is mutagenic and genotoxic in mammalian cells. Etoposide caused aberrations in chromosome number and structure in embryonic murine cells and human hematopoietic cells, gene mutations in Chinese hamster ovary cells, and DNA damage by strand breakage and DNA-protein cross-links in mouse leukemia cells; it also caused a dose-related increase in sister chromatid exchanges in Chinese hamster ovary cells and was mutagenic in the Ames test {01} {18}.

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients receiving antineoplastic therapy, especially with the alkylating agents. In general, these effects appear to be related to dose and length of therapy and may be irreversible. Prediction of the degree of testicular or ovarian function impairment is complicated by the common use of combinations of several antineoplastics, which makes it difficult to assess the effects of individual agents.

Pregnancy—
Adequate and well-controlled studies in humans have not been done.

First trimester: It is usually recommended that use of antineoplastics, especially combination chemotherapy, be avoided whenever possible, especially during the first trimester. Although information is limited because of the relatively few instances of antineoplastic administration during pregnancy, the mutagenic, teratogenic, and carcinogenic potential of these medications must be considered.

Other hazards to the fetus include adverse reactions seen in adults.

In general, use of a contraceptive is recommended during cytotoxic drug therapy.

Etoposide has been shown to be teratogenic and embryotoxic in mice and rats. Dose-related maternal toxicity, embryotoxicity, and teratogenicity (major skeletal abnormalities, exencephaly, encephalocele, and anophthalmia) have been reported with intravenous administration of 0.4 mg of etoposide per kg of body weight per day (mg/kg per day) (one twentieth of the recommended clinical dose based on body surface area) to rats during organogenesis; doses of 1.2 and 3.6 mg/kg per day (one seventh and one half of the recommended clinical dose, respectively, based on body surface area) caused 90% and 100% embryonic resorptions, respectively. Embryotoxicity and teratogenicity (cranial abnormalities, major skeletal abnormalities) also have been reported in mice following intraperitoneal administration of 1 mg/kg (one sixteenth of the recommended clinical dose based on body surface area) on day 6, 7, or 8 of gestation; intraperitoneal administration of 1.5 mg/kg (one tenth of the recommended clinical dose based on body surface area) on day 7 of gestation caused an increase in the incidences of intrauterine fetal death, fetal malformations, and decreased fetal weights {18}. Risk-benefit must be carefully considered when this medication is required in life-threatening situations or in serious diseases for which other medications cannot be used or are ineffective.

FDA Pregnancy Category D.

Breast-feeding

Etoposide is distributed into breast milk. Breast-feeding is not recommended during chemotherapy because of the risks to the infant (adverse effects, mutagenicity, carcinogenicity).

Pediatrics

Appropriate studies on the relationship of age to the effects of etoposide have not been performed in the pediatric population. However, use of higher-than-recommended dosages of etoposide has been associated with a higher incidence of anaphylactic reactions in the pediatric population {18}.


Geriatrics


No information is available on the relationship of age to the effects of etoposide in geriatric patients. However, elderly patients are more likely to have age-related renal function impairment, which may require adjustment of dosage in patients receiving etoposide {18}.


Dental

The bone marrow depressant effects of etoposide may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Dental work, whenever possible, should be completed prior to initiation of therapy or deferred until blood counts have returned to normal. Patients should be instructed in proper oral hygiene during treatment, including caution in use of regular toothbrushes, dental floss, and toothpicks.

Etoposide may also cause stomatitis, which may be associated with considerable discomfort.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Blood dyscrasia–causing medications (see Appendix II )    (leukopenic and/or thrombocytopenic effects of etoposide may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of etoposide, if necessary, should be based on blood counts )


» Bone marrow depressants, other (see Appendix II ) or
Radiation therapy    (additive bone marrow depression may occur; dosage reduction may be required when two or more bone marrow depressants, including radiation, are used concurrently or consecutively)


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by etoposide therapy, the patient's antibody response to the vaccine may be decreased. The interval between discontinuation of medications that cause immunosuppression and restoration of the patient's ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year)


» Vaccines, live virus    (because normal defense mechanisms may be suppressed by etoposide therapy, concurrent use with a live virus vaccine may potentiate the replication of the vaccine virus, may increase the side/adverse effects of the vaccine virus, and/or may decrease the patients antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patients hematologic status and only with the knowledge and consent of the physician managing the etoposide therapy. The interval between discontinuation of medications that cause immunosuppression and restoration of the patients ability to respond to the vaccine depends on the intensity and type of immunosuppression-causing medication used, the underlying disease, and other factors; estimates vary from 3 months to 1 year. Patients with leukemia in remission should not receive live virus vaccine until at least 3 months after their last chemotherapy. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Bone marrow depression
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease)


Hepatic function impairment    (reduced clearance {01})


» Infection
Renal function impairment    (reduced elimination {01}; lower dosage may be necessary )


Sensitivity to etoposide {01}
» Caution should be used also in patients who have had previous cytotoxic drug therapy or radiation therapy.

Patient monitoring
The following are especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Examination of patients mouth for ulceration    (recommended prior to each dose)


» Hematocrit or hemoglobin and
» Leukocyte count, total and, if appropriate, differential and
» Platelet count    (determinations recommended prior to initiation of therapy and at periodic intervals during therapy; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Albumin, serum    (low concentrations may be associated with increased risk of etoposide-related toxicities {19})




Side/Adverse Effects

Note: Many “side effects” of antineoplastic therapy are unavoidable and represent the medication's pharmacologic action. Some of these (for example, leukopenia and thrombocytopenia) actually are used as parameters to aid in individual dosage titration.
Hypotension may occur temporarily if etoposide is administered by intravenous infusion over a period of less than 30 minutes.
Use of higher-than-recommended doses has been associated with hepatic toxicity and metabolic acidosis {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Anemia {01} ( unusual tiredness or weakness)
    
leukopenia (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)— usually asymptomatic
    
thrombocytopenia (unusual bleeding or bruising ; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)— usually asymptomatic

Note: With leukopenia, the nadir of the granulocyte count occurs 7 to 14 days after administration, and recovery is usually complete by the 20th day; cumulative myelosuppression has not been reported.
With thrombocytopenia, the nadir of the platelet count occurs 9 to 16 days after administration, and recovery is usually complete by the 20th day; cumulative myelosuppression has not been reported.


Incidence less frequent
    
Stomatitis (sores in mouth or on lips)

Incidence rare
    
Anaphylaxis (fast heartbeat ; fever or chills; shortness of breath or wheezing; back pain; cough; loss of consciousness; sweating; swelling of face or tongue; tightness in throat {01})
    
chemical phlebitis ( pain at site of injection)
    
neurotoxicity (difficulty in walking; numbness or tingling in fingers and toes; weakness)
    
skin rash or itching {01}

Note: Anaphylaxis also is associated with hypotension {01}; hypertension and flushing also have been reported {01}; blood pressure usually returns to normal within a few hours after the intravenous infusion is discontinued {01}. An apparent hypersensitivity-associated apnea has been reported rarely {01}. Use of higher-than-recommended dosages of etoposide has been associated with a higher rate of anaphylaxis in pediatric patients {18}. Rarely, anaphylaxis may be fatal.
At investigational doses, a generalized pruritic erythematous maculopapular rash, consistent with perivasculitis, has been reported {01}.




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Loss of appetite
    
nausea and vomiting

Incidence less frequent
    
Central nervous system (CNS) toxicity (unusual tiredness )
    
diarrhea



Those not indicating need for medical attention
Incidence more frequent
    
Alopecia (loss of hair)

Note: Alopecia sometimes progresses to total baldness; it is reversible {01}.






Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Etoposide (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to etoposide

Pregnancy—Use not recommended because of mutagenic, teratogenic, and carcinogenic potential; advisability of using contraception; telling physician immediately if pregnancy is suspected





Breast-feeding—Not recommended because of risk of serious side effects





Use in children—Severe allergic reactions can occur if children receive higher-than-recommended doses

Other medications, especially other bone marrow depressants or previous cytotoxic drug or radiation therapy
Other medical problems, especially chickenpox, herpes zoster, or infection

Proper use of this medication
» Importance of not taking more or less medication than the amount prescribed

Caution in taking combination therapy; taking each medication at the right time

Frequency of nausea, vomiting, and loss of appetite; importance of continuing medication despite stomach upset

Checking with physician if vomiting occurs shortly after oral dose is taken

» Proper dosing
Missed dose: Not taking at all; not doubling doses

» Proper storage

Precautions while using this medication
» Importance of close monitoring by physician

» Avoiding immunizations unless approved by physician; other persons in patient's household should avoid immunizations with oral poliovirus vaccine; avoiding persons who have taken oral poliovirus vaccine or wearing a protective mask that covers nose and mouth

Caution if bone marrow depression occurs
» Avoiding exposure to persons with infections, especially during periods of low blood counts; checking with physician immediately if fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination occurs

» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur

Caution in use of regular toothbrush, dental floss, or toothpick; physician, dentist, or nurse may suggest alternatives; checking with physician before having dental work done

Not touching eyes or inside of nose unless hands are washed immediately before

Using caution to avoid accidental cuts with use of sharp objects such as safety razor or fingernail or toenail cutters

Avoiding contact sports or other situations where bruising or injury could occur


Side/adverse effects
Importance of discussing possible effects, including cancer, with physician

Signs of potential side effects, especially anemia, leukopenia, thrombocytopenia, stomatitis, anaphylaxis, chemical phlebitis, neurotoxicity, and skin rash or itching

Physician or nurse can help in dealing with side effects

Possibility of hair loss; normal hair growth should resume after treatment has ended


General Dosing Information
Patients receiving etoposide should be under supervision of a physician experienced in cancer chemotherapy.

A variety of dosage schedules of etoposide, alone or in combination with other antitumor agents, are used. The prescriber may consult the medical literature as well as the manufacturer's literature in choosing a specific dosage.

Dosage must be adjusted to meet the individual requirements of each patient, based on clinical response and appearance of or severity of toxicity.

Frequency and duration of nausea and vomiting may be reduced in some patients by administration of antiemetics prior to dosing.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of etoposide. These may include extreme care in performing invasive procedures; regular inspection of intravenous sites, skin (including perirectal area), and mucous membrane surfaces for signs of bleeding or bruising; limiting frequency of venipuncture and avoiding intramuscular injections; testing urine, emesis, stool, and secretions for occult blood; care in use of regular toothbrushes, dental floss, toothpicks, safety razors, and fingernail and toenail cutters; avoiding constipation; and using caution to prevent falls and other injuries. Such patients should avoid alcohol and aspirin intake because of the risk of gastrointestinal bleeding. Platelet transfusions may be required.

Patients who develop leukopenia should be observed carefully for signs of infection. Antibiotic support may be required. In neutropenic patients who develop fever, broad-spectrum antibiotic coverage should be initiated empirically, pending bacterial cultures and appropriate diagnostic tests.

It is recommended that the dosage of etoposide be reduced in patients with renal function impairment. A dose reduction of 25% is recommended if creatinine clearance is 15 to 50 mL per minute {18}.

For parenteral dosage form only
It is recommended that etoposide injection be diluted prior to use, and that it be administered by slow intravenous infusion over a period of 30 to 60 minutes to prevent hypotension. Etoposide should not be administered by rapid intravenous injection {01} or by any other route.

Etoposide phosphate may be administered intravenously over 5 to 210 minutes {19}.

Safety considerations for handling this medication
There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents, although the actual risk is unknown. USP advisory panels recommend cautious handling both in preparation and disposal of antineoplastic agents. Precautions that have been suggested include:    • Use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks.
   • Use of proper technique to prevent contamination of the medication, work area, and operator during transfer between containers (including proper training of personnel in this technique).
   • Cautious and proper disposal of needles, syringes, vials, ampuls, and unused medication.
A number of medical centers have developed detailed guidelines for handling of antineoplastic agents.


Combination chemotherapy
Etoposide may be used in combination with other agents in various regimens. As a result, incidence and/or severity of side effects may be altered and different dosages (usually reduced) may be used. For example, etoposide is part of the following chemotherapeutic combinations (some commonly used acronyms are in parentheses):    —etoposide, cyclophosphamide, doxorubicin, and vincristine (CAVE).
   —cyclophosphamide, doxorubicin, and etoposide (CAE).
   —cisplatin, bleomycin, and etoposide (BEP).
   —cisplatin and etoposide (EP).
For specific dosages and schedules, consult the literature. For information regarding each agent, consult the individual monograph.

For treatment of adverse effects
Hypotension may be treated by stopping the infusion, administering fluids and other supportive treatment, then resuming the infusion at a slower rate.

Anaphylaxis should be treated by stopping the infusion and administering pressor agents, corticosteroids, antihistamines, or volume expanders as necessary.


Oral Dosage Forms

Note: Bracketed information in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.


ETOPOSIDE CAPSULES, USP

Note: The dosing and strengths of the dosage forms available are expressed in terms of etoposide base (not the phosphate salt).


Usual adult dose
Small cell lung carcinoma
Oral, 70 mg (base) per square meter of body surface area (rounded to the nearest 50 mg) per day for four days to 100 mg per square meter of body surface area (rounded to the nearest 50 mg) per day for five days, repeated every three to four weeks.

[Carcinoma, unknown primary site ]1
Patients have benefited from an oral daily dose of 50 mg alternating with 100 mg, on days 1 to 10 of a 21–day treatment cycle, combined with intravenous paclitaxel and carboplatin, for 4 to 8 cycles.{114}


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


50 mg (base) (Rx) [VePesid]

Canada—


50 mg (base) (Rx) [VePesid]

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), in a tight container. Protect from freezing.



Parenteral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

ETOPOSIDE INJECTION

Usual adult dose
Germ cell testicular tumors
Intravenous infusion, 50 to 100 mg (base) per square meter of body surface area per day on days 1 through 5 to 100 mg per square meter of body surface area on days 1, 3, and 5 of a regimen that is repeated every three to four weeks {01}.

Small cell lung carcinoma
Intravenous infusion, 35 mg (base) per square meter of body surface area per day for four days to 50 mg per square meter of body surface area per day for five days, repeated every three to four weeks.

[Lymphomas, Hodgkin's]1 or
[Lymphomas, non-Hodgkin's]or
[Lymphomas, cutaneous T-cell ]1 or
[Leukemia, acute nonlymphocytic]1 or
[Leukemia, acute lymphocytic]1or
[Multiple myeloma]1 or
[Ewing's sarcoma]1or
[Kaposi's sarcoma, autoimmune deficiency syndrome (AIDS)–associated]1or
[Sarcomas, soft tissue]1 or
[Osteosarcoma ]1or
[ Carcinoma, adrenocortical]1 or
[Carcinoma, gastric]1or
[Carcinoma, lung, non–small cell] or
[ Carcinoma, endometrial]1or
[Hepatoblastoma]1 or
[Neuroblastoma ]1or
[ Retinoblastoma ]1 or
[Thymoma]1or
[Wilms' tumor]1 or
[Tumors, brain, primary]1or
[Tumors, trophoblastic, gestational]1 or
[Tumors, germ cell, ovarian]1
Consult medical literature and manufacturer's literature for specific dosage.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


20 mg (base) per mL (Rx) [VePesid (citric acid 2 mg per mL) (benzyl alcohol 30 mg per mL) (polysorbate 80/tween 80, 80 mg per mL) ( polyethylene glycol 300, 650 mg per mL) (alcohol 30.5% v/v)] [Toposar (citric acid 2 mg per mL) (benzyl alcohol 30 mg per mL) (polysorbate 80/tween 80, 80 mg per mL) ( polyethylene glycol 300, 650 mg per mL) (alcohol 30.5% v/v)][Generic]

Canada—


20 mg (base) per mL (Rx) [VePesid (benzyl alcohol 30 mg per mL ) (citric acid) (polyethylene glycol 300) (polysorbate 80) ( ethanol)][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by the manufacturer. Protect from freezing.

Preparation of dosage form:
Etoposide injection may be diluted for administration by intravenous infusion in either 5% dextrose injection or 0.9% sodium chloride injection to produce a solution containing 200 to 400 mcg (0.2 to 0.4 mg) of etoposide per mL (precipitation may occur with concentrations greater than 400 mcg per mL) {01}.

Cracking and leaking of plastic containers made of ABS (a polymer composed of acrylonitrile, butadiene, and styrene) has been reported when used with undiluted (but not diluted) etoposide injection {01}.

Stability:
When diluted as recommended, 0.2 and 0.4 mg per mL solutions are stable for 96 and 24 hours, respectively, at 25 °C (77 °F) under normal room fluorescent light in glass or plastic containers {01}.


Caution:
Use of products containing benzyl alcohol is generally not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.

Use of products containing polysorbate 80 is generally not recommended for preparation of medications for use in premature infants. A life-threatening syndrome consisting of hepatic and renal failure, pulmonary deterioration, thrombocytopenia, and ascites has been associated with this use {01}.


ETOPOSIDE PHOSPHATE FOR INJECTION

Note: The dosage and strength of the available dosage form are expressed in terms of etoposide base (not the phosphate salt).


Usual adult dose
Germ cell testicular tumors
Intravenous infusion, 50 to 100 mg (base) per square meter of body surface area per day on days 1 through 5 to 100 mg per square meter of body surface area on days 1, 3, and 5 of a regimen that is repeated every three to four weeks {17}.

Small cell lung carcinoma
Intravenous infusion, 35 mg (base) per square meter of body surface area per day for four days to 50 mg per square meter of body surface area per day for five days, repeated every three to four weeks.

[Lymphomas, Hodgkin's]1 or
[Lymphomas, non-Hodgkin's]or
[Lymphomas, cutaneous T-cell ]1 or
[Leukemia, acute nonlymphocytic]1 or
[Leukemia, acute lymphocytic]1or
[Multiple myeloma]1 or
[Ewing's sarcoma]1or
[Kaposi's sarcoma, autoimmune deficiency syndrome (AIDS)–associated]1or
[Sarcomas, soft tissue]1 or
[Osteosarcoma ]1or
[ Carcinoma, adrenocortical]1 or
[Carcinoma, gastric]1or
[Carcinoma, lung, non–small cell] or
[ Carcinoma, endometrial]1or
[Hepatoblastoma]1 or
[Neuroblastoma ]1or
[ Retinoblastoma ]1 or
[Thymoma]1or
[Wilms' tumor ]1 or
[Tumors, brain, primary]1or
[Tumors, trophoblastic, gestational]1 or
[Tumors, germ cell, ovarian ]1
Consult medical literature and manufacturer's literature for specific dosage.


Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—


100 mg (base) (Rx) [Etopophos (sodium citrate 32.7 mg) (dextran 40, 300 mg)]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F), unless otherwise specified by the manufacturer {17}.

Preparation of dosage form:
Etoposide phosphate for injection is reconstituted for intravenous use by the addition of 5 or 10 mL of either sterile water for injection, 5% dextrose injection, 0.9% sodium chloride injection, bacteriostatic water for injection with benzyl alcohol, or bacteriostatic sodium chloride for injection with benzyl alcohol, producing a solution containing 20 mg or 10 mg etoposide per mL (22.7 mg or 11.4 mg etoposide phosphate per mL), respectively. Following reconstitution, etoposide phosphate may be administered without further dilution, or it may be further diluted with 5% dextrose injection or 0.9% sodium chloride injection to a final concentration as low as 0.1 mg etoposide per mL {17}.

Stability:
When diluted as recommended, etoposide phosphate solution is stable for 24 hours at controlled room temperature (20 to 25 °C [68 to 77 °F]) or in a refrigerator (2 to 8 °C [36 to 46 °F]) {17}.


Caution:
Use of products containing benzyl alcohol is generally not recommended for preparation of medications for use in neonates. A fatal toxic syndrome consisting of metabolic acidosis, CNS depression, respiratory problems, renal failure, hypotension, and possibly seizures and intracranial hemorrhages has been associated with this use.



Revised: 12/2122002



References
  1. VePesid package insert (Bristol—US), Rev 9/88; Rev 12/88; Rev 4/89; Rev 3/91. In: Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data Production Company; 1994.
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2230.
  1. Reviewers' responses to Hematology-Oncology Advisory Panel Memo #26 of 8/28/89.
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2062.
  1. VePesid package insert (Bristol—Canada), Rev 9/2/86, Rec 3/9/88.
  1. Panel comment, 6/94.
  1. Phillips NC. Oral etoposide. Drug Intell Clin Pharm 1988 Nov; 22: 860-3.
  1. Sinkule JA. Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology/pharmacokinetics, adverse effects and use as an antineoplastic agent. Pharmacotherapy 1984 Mar/Apr; 4: 61-73.
  1. Fleming RA, Miller AA, Stewart CF. Etoposide: an update. Clin Pharm 1989 Apr; 8: 274-93.
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1667.
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1501.
  1. Drug evaluations subscription. Chicago: American Medical Association; 1993. III/ONC 1:25-31.
  1. Dorr RT, Von Hoff DD. Cancer chemotherapy handbook. 2nd ed. East Norwalk, CT: Appleton & Lange; 1993.
  1. Drugs of choice for cancer chemotherapy. Med Lett Drugs Ther 1993 May 28; 35: 43-50.
  1. Pizzo PA, Poplack DG, editors. Principles and practice of pediatric oncology. 2nd ed. Philadelphia: JB Lippincott Company; 1993.
  1. Reviewers' responses to Hematology-Oncology Advisory Panel Memo #9 of 1/30/97.
  1. Etopophos package insert (Bristol-Myers Squibb—US), Rev 9/96, Rec 12/16/96.
  1. VePesid package insert (Bristol-Myers Squibb—US), Rev 8/96, Rec 5/97.
  1. VePesid package insert (Bristol-Myers Squibb—Canada), Rev 12/2/94, Rec 1/12/95.
  1. Panel comment, 7/97.
  1. Panel comment, 7/97.
  1. Panel comment, 7/97.
  1. Panel comment, 7/97.
  1. Devita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 1043-4.
  1. Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: United States Pharmacopeial Convention Inc; 1997. p. 294.
  1. Giaccone G, Ardizzoni A, Kirkpatrick A, et al. Cisplatin and etoposide combination chemotherapy for locally advanced or metastatic thymoma: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 1996; 14: 814-20.
  1. Oshita F, Kasai T, Kurata T, et al. Intensive chemotherapy with cisplatin, doxorubicin, cyclophosphamide, etoposide and granulocyte colony-stimulating factor for advanced thymoma or thymic cancer: preliminary results. Jpn J Clin Oncol 1995; 25: 208-12.
  1. Macchiarini P, Chella A, Ducci F, et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 1991; 68: 706-13.
  1. Gaspard MH, Maraninchi D, Stoppa AM, et al. Intensive chemotherapy with high doses of BCNU, etoposide, cytosine arabinoside, and melphalan (BEAM) followed by autologous bone marrow transplantation: toxicity and antitumor activity in 26 patients with poor-risk malignancies. Cancer Chemother Pharmacol 1988; 22: 256-62.
  1. Giaccone G, Musella R, Bertetto O, et al. Cisplatin-containing chemotherapy in the treatment of invasive thymoma: report of five cases. Cancer Treat Rep 1985; 69: 695-7.
  1. Pierga JY, Dieras V, Beuzeboc P, et al. Phase II trial of doxorubicin, 5-fluorouracil, etoposide, and cisplatin in advanced or recurrent endometrial carcinoma. Gynecol Oncol 1997; 66: 246-9.
  1. Pierga JY, Dieras V, Paraiso D, et al. Treatment of advanced or recurrent endometrial carcinoma with combination of etoposide, cisplatin, and 5-fluorouracil: a phase II study. Gynecol Oncol 1996; 60: 59-63.
  1. Cornelison TL, Baker TR, Piver MS, et al. Cisplatin, adriamycin, etoposide, megestrol acetate versus melphalan, 5-fluorouracil, medroxyprogesterone acetate in the treatment of endometrial carcinoma. Gynecol Oncol 1995; 59: 243-8.
  1. Piver MS, Fanning J, Baker TR. Phase II trial of cisplatin, adriamycin, and etoposide for metastatic endometrial adenocarcinoma. Am J Clin Oncol 1991; 14: 200-2.
  1. Slayton RE, Blessing JA, Delgado G. Phase II trial of etoposide in the management of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. Cancer Treat Rep 1982; 66: 1669-71.
  1. Madreperla SA, Hungerford JL, Doughty D, et al. Treatment of retinoblastoma vitreous base seeding. Ophthalmology 1998; 105: 121-4.
  1. Shields CL, Shields JA, Needle M, et al. Combined chemoreduction and adjuvant treatment for intraocular retinoblastoma. Ophthalmology 1997; 104: 2101-11.
  1. Bornfeld N, Schuler A, Bechrakis N, et al. Preliminary results of primary chemotherapy in retinoblastoma. Klin Padiatr 1997; 209: 216-21.
  1. Schvartzman E, Chantada G, Fandino A, et al. Results of a stage-based protocol for the treatment of retinoblastoma. J Clin Oncol 1996; 14: 1532-6.
  1. Greenwald MJ, Strauss LC. Treatment of intraocular retinoblastoma with carboplatin and etoposide chemotherapy. Ophthalmology 1996; 103: 1989-97.
  1. Murphree AL, Villablanca JG, Deegan WF, et al. Chemotherapy plus local treatment in the management of intraocular retinoblastoma. Arch Ophthalmol 1996; 114: 1348-56.
  1. Kingston JE, Hungerford JL, Madreperla SA, et al. Results of combined chemotherapy and radiotherapy for advanced intraocular retinoblastoma. Arch Ophthalmol 1996; 114: 1339-43.
  1. Shields CL, De Potter P, Himelstein BP, et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol 1996; 114: 1330-8.
  1. Strauss LC, Greenwald MJ. Carboplatin and VP-16 chemotherapy, plus local therapies, for initial treatment of advanced intraocular retinoblastoma [abstract 1451]. Proc Ann Meet Am Soc Clin Oncol 1996; 462.
  1. Doz F, Neuenschwander S, Plantaz D, et al. Etoposide and carboplatin in extraocular retinoblastoma: a study by the Societe Francaise d'Oncologie Pediatrique. J Clin Oncol 1995; 13: 902-9.
  1. Pratt CB, Fontanesi J, Chenaille P, et al. Chemotherapy for extraocular retinoblastoma. Pediatr Hematol Oncol 1994; 11: 301-9.
  1. Advani SH, Rao SR, Iyer RS, et al. Pilot study of sequential combination chemotherapy in advanced and recurrent retinoblastoma. Med Pediatr Oncol 1994; 22: 125-8.
  1. Carpenter PA, White L, McCowage G, et al. A dose-intensive, cyclophosphamide-based regimen for the treatment of recurrent/progressive or advanced solid tumors of childhood: a report from the Australian and New Zealand Children's Cancer Study Group. Cancer 1997; 80: 489-96.
  1. Hempel L, Kremens B, Weirich A, et al. High dose consolidation with autologous stem cell rescue (ASCR) for nephroblastoma initially treated according to the SIOP 9/GPOH trial and study. Klin Padiatr 1996; 208: 186-9.
  1. Kung FH, Desai SJ, Dickerman JD, et al. Ifosfamide/carboplatin/etoposide (ICE) for recurrent malignant solid tumors of childhood: a Pediatric Oncology Group phase I/II study. J Pediatr Hematol Oncol 1995; 17: 265-9.
  1. Pein F, Michon J, Valteau-Couanet D, et al. High dose melphalan, etoposide and carboplatin with bone marrow transplantation as consolidation therapy in high risk Wilms' tumors [abstract P-140]. Med Pediatr Oncol 1995; 25: 313.
  1. Pein F, Tournade MF, Zucker JM, 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.
  1. Malogolowkin MH, Feusner J, Steele DA, et al. Carboplatin (CBDCA)/etoposide (VP16) for the treatment of children with high-risk (HR) or recurrent Wilms' tumor (RWT) [abstract 1453]. Proc Ann Meet Am Soc Clin Oncol 1994; 13: 424.
  1. Kung FH, Pratt CB, Vega RA, et al. Ifosfamide/etoposide combination in the treatment of recurrent malignant solid tumors of childhood: a Pediatric Oncology Group phase II study. Cancer 1993; 71: 1898-1903.
  1. Pein F, Pinkerton R, Tournade MF, et al. Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group. J Clin Oncol 1993; 11: 1478-81.
  1. Miser J, Krailo M, Hammond GD. The combination of ifosfamide (IFOS), etoposide (VP16), and mesna (M): a very active regimen in the treatment of recurrent Wilms' tumor (WT) [abstract 1432]. Proc Annu Meet Am Soc Clin Oncol 1993; 12: 417.
  1. Warkentin PI, Brochstein JA, Strandjord SE, et al. High dose therapy followed by autologous stem cell rescue for recurrent Wilms' tumor (WT) [abstract 1418]. Proc Ann Meet Am Soc Clin Oncol 1993; 12: 414.
  1. van Hoff J, Grier H, Douglass E, et al. Etoposide, ifosfamide and cisplatin (VIP) therapy in refractory childhood solid tumors: response and toxicity [abstract 1268]. Proc Ann Meet Am Soc Clin Oncol 1992: 11: 368.
  1. Castello MA, Clerico A, Jenkner A, et al. A pilot study of high-dose carboplatin and pulsed etoposide in the treatment of childhood solid tumors. Pediatr Hematol Oncol 1990; 7: 129-35.
  1. Kung F, Hayes FA, Krischer J, et al. Clinical trial of etoposide (VP-16) in children with recurrent malignant solid tumors: a phase II study from the Pediatric Oncology Group. Invest New Drugs 1988; 6: 31-6.
  1. Perin G, Dallorsos S, Stura M, et al. High-dose cisplatin and etoposide in advanced malignancies of childhood. Pediatr Hematol Oncol 1987; 4: 329-36.
  1. Loh W, Ortega JA, Wolff J, et al. Cis-platinum/VP 16 for the retrieval of Wilms' tumor relapsing on chemotherapy [abstract 876]. Proc Ann Meet Am Soc Clin Oncol 1987; 6: 222.
  1. Chard RL, 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.
  1. Genet JC, Brunat-Mentigny M, Demaille MC, et al. Ifosfamide and etoposide in childhood osteosarcoma: a Phase II study of the French Society of Paediatric Oncology. Eur J Cancer 1997; 33: 232-7.
  1. Cassano WF, Graham-Pole J, Dickson N. Etoposide, cyclophosphamide, cisplatin, and doxorubicin as neoadjuvant chemotherapy for osteosarcoma. Cancer 1991; 68: 1899-1902.
  1. Miser JS, Kinsella TJ, Triche TJ. Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987; 5: 1191-8.
  1. Saleh RA, Graham-Pole J, Cassano et al. Response of osteogenic sarcoma to the combination of etoposide and cyclophosphamide as neoadjuvant chemotherapy. Cancer 1990; 65: 861-5.
  1. Bacci G, Picci P, Ferrari S, et al. Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin. Cancer 72: 3227-38.
  1. Cushing B, Giller R, Marina N, et al. Results of surgery alone or surgery plus cisplatin, etoposide and bleomycin (PEB) in children with localized gonadal malignant germ cell tumor (MGCT): a pediatric intergroup report (POG 9048/CCG 8891)[abstract 1840]. Proc Ann Meet Am Soc Clin Oncol 1997; 16: 511.
  1. Lopes LF, de Carmargo B, Dondonis M, et al. Response to high-dose cisplatin and etoposide in advanced germ cell tumors in children: results of the Brazilian Germ Cell Tumor Study. Med Pediatr Oncol 1995; 25: 396-9.
  1. Williams S, Blessing JA, Liao SY, et al. Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group. J Clin Oncol 1994; 12: 701-6.
  1. Culine S, Kattan J, Lhomme C, et al. A phase II study of high-dose cisplatin, vinblastine, bleomycin, and etoposide (PVeBV regimen) in malignant nondysgerminomatous germ-cell tumors of the ovary. Gynecol Oncol 1994; 54: 47-53.
  1. Mayordomo JI, Paz-Ares L, Rivera F, et al. Ovarian and extragonadal malignant germ-cell tumors in females: a single-institution experience with 43 patients. Ann Oncol 1994; 5: 225-31.
  1. Loehrer PJ, Einhorn LH, Elson P, et al. Phase III study of cisplatin (P) plus etoposide (VP16) with either bleomycin (B) or ifosfamide (I) in advanced stage germ cell tumors (GCT): an intergroup trial [abstract 831]. Proc Ann Meet Am Soc Clin Oncol 1993; 12: 261.
  1. Williams SD, Blessing JA, Hatch KD, et al. Chemotherapy of advanced dysgerminoma: trials of the Gynecologic Oncology Group. J Clin Oncol 1991; 9: 1950-5.
  1. Gershenson DM, Morris M, Cangir A, et al. Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin. J Clin Oncol 1990; 8: 715-20.
  1. Wong LC, Collins RJ, Mgan HY, et al. Etoposide combination chemotherapy in refractory ovarian malignant germ cell tumor. Gynecol Oncol 1990; 39: 123-6.
  1. Germa JR, Piera KM, Barnadas A, et al. Sequential combination chemotherapy for malignant germ cell tumors of the ovary. Cancer 1988; 61: 913-8.
  1. Smales E, Peckham MJ. Chemotherapy of germ-cell ovarian tumours: first-line treatment with etoposide, bleomycin and cisplatin or carboplatin. Eur J Cancer Clin Oncol 1987; 23: 469-74.
  1. Pinkerton CR, Pritchard J, Spitz L. High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy. J Clin Oncol 1986; 4: 194-9.
  1. Smith EB, Clarke-Pearson DL, Creasman WT. A VP-16-213- and cisplatin-containing regimen for treatment of refractory ovarian germ cell malignancies. Am J Obstet Gynecol 1984; 150: 927-31.
  1. Horwich A, Sleijfer DT, Fossa SD, et al. Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer trial. J Clin Oncol 1997; 15: 1844-52.
  1. Bokemeyer C, Kohrmann O, Tischler J, et al. A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with “good-risk” metastatic non-seminomatous germ cell tumors. Ann Oncol 1996; 7(10): 1015-21.
  1. Bosl GJ, Bajorin DF. Etoposide plus carboplatin or cisplatin in good-risk patients with germ cell tumors: a randomized comparison. Semin Oncol 1994; 21(5 Suppl 12): 61-4.
  1. 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.
  1. Wozniak AJ, Samson MK, Shah NT, et al. A randomized trial of cisplatin, vinblastine, and bleomycin versus vinblastine, cisplatin, and etoposide in the treatment of advanced germ cell tumors of the testis: a Southwest Oncology Group study. J Clin Oncol 1991; 9: 70-6.
  1. Bosl GJ, Geller NL, Bajorin D, et al. A randomized trial of etoposide + cisplatin versus vinblastine + bleomycin + cisplatin + cyclophosphamide + dactinomycin in patients with good-prognosis germ cell tumors. J Clin Oncol 1988; 6: 1231-8.
  1. 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.
  1. Cullen MH, Stenning SP, Parkinson MC, et al. Short-course adjuvant chemotherapy in high-risk stage I nonseminomatous germ cell tumors of the testis: a Medical Research Council report. J Clin Oncol 1996; 14: 1106-13.
  1. Pont J, Albrecht W, Postner G, et al. Adjuvant chemotherapy for high-risk clinical stage I nonseminomatous testicular germ cell cancer: long-term results of a prospective trial. J Clin Oncol 1996; 14: 441-8.
  1. Farhat F, Culine S, Theodore C, et al. Cisplatin and ifosfamide with either vinblastine or etoposide as salvage therapy for refractory or relapsing germ cell tumor patients: the Institut Gustave Roussy experience. Cancer 1996; 77: 1193-7.
  1. Motzer RJ, Sheinfeld J, Mazumdar M, et al. Etoposide and cisplatin adjuvant therapy for patients with pathologic stage II germ cell tumors. J Clin Oncol 1995; 13: 2700-4.
  1. Haas RJ, Schhmidt P, Gobel U, et al. Treatment of malignant testicular tumors in childhood: results of the German National Study 1982-1992. Med Pediatr Oncol 1994; 23: 400-5.
  1. Tjulandin SA, Garin AM, Mescheryakov AA, et al. Cisplatin-etoposide and carboplatin-etoposide induction chemotherapy for good-risk patients with germ cell tumors. Ann Oncol 1993; 4(8): 663-7.
  1. Kattan J, Mahjoubi M, Droz JP, et al. High failure rate of carboplatin-etoposide combination in good risk non-seminomatous germ cell tumours. Eur J Cancer 1993; 29A: 1504-19.
  1. Germa JR, Sagarra AF, Izquierdo MA, et al. Sequential trials of cisplatin, vinblastine, and bleomycin and etoposide and cisplatin in disseminated nonseminomatous germ cell tumors of the testis with a good prognosis at a single institution. Cancer 1993; 71: 796-803.
  1. Husband DJ, Green JA. POMB/ACE chemotherapy in non-seminomatous germ cell tumours: outcome and importance of dose intensity. Eur J Cancer 1992; 28: 86-91.
  1. Pizzocaro G, Salvioni R, Piva L, et al. Modified cisplatin, etoposide (or vinblastine) and ifosfamide salvage therapy for male germ-cell tumors: long-term results. Ann Oncol 1992; 3(3): 211-6.
  1. Bajorin DF, Geller NL, Welsen SF, et al. Two-drug therapy in patients with metastatic germ cell tumors. Cancer 1991; 67: 28-32.
  1. 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.
  1. Bosl GJ, Geller NL, Vogelzang NJ, et al. Alternating cycles of etoposide plus cisplatin and VAB-6 in the treatment of poor-risk patients with germ cell tumors. J Clin Oncol 1987; 5: 436-40.
  1. Hainsworth JD, Williams SD, Einhorn LH, et al. Successful treatment of resistant germinal neoplasms with VP-16 and cisplatin: results of a Southeastern Cancer Group trial. J Clin Oncol 1985; 3: 666-71.
  1. Hussain MH, Pienta KJ, Redman BG, et al. Oral etoposide in the treatment of hormone-refractory prostate cancer. Cancer 1994 Jul; 74(1): 100-3.
  1. Pienta KJ, Redman B, Hussain M, et al. Phase II evaluation of oral estramustine and oral etoposide in hormone-refractory adenocarcinoma of the prostate. J Clin Oncol 1994 Oct; 12(10): 2005-12.
  1. Pienta KJ, Redman BG, Bandekar R, et al. A phase II trial of oral estramustine and oral etoposide in hormone refractory prostate cancer. Urology. 1997 Sep; 50(3): 401-6.
  1. Smith D, Esper P, Strawderman M, et al. Phase II trial of oral estramustine, oral etoposide and intravenous paclitaxel in hormone-refractory prostate cancer. J Clin Oncol. 1999 Jun; 17(6): 1664-71.
  1. Colleoni M, Graiff C, Vicario G, et al. Phase II study of estramustine,oral etoposide, and vinorelbine in hormone-refractory prostate cancer. Am J Clin Oncol. 1997 Aug; 20(4): 383-6.
  1. Dimopoulos MA, Panopoulos C, Bamia C, et al. Oral estramustine and oral etoposide for hormone-refractory prostate cancer. Urology 1997; 50(5): 754-8.
  1. Smith DC, Esper PS, Pienta KJ. Estramustine and etoposide (EE) in patients with a rising prostate-specific antigen (PSA) after definitive primary therapy: a phase II trial. Proc Am Soc Clin Oncol 1997; 16: 344a [Abst 1229].
  1. Pienta KJ, Flaherty LE, Hussain M, et al. Report of an extended phase II trial of oral estramustine and oral etoposide in the treatment of hormone refractory prostate cancer patients. Proc Am Soc Clin Oncol 1996 Mar; 15: 261 [Abst 681].
  1. Maulard-Durdux C, Dufour B, Hennequin C, et al. Phase II study of the oral cyclophosphamide and etoposide combination in hormone-refractory prostate carcinoma patients. Cancer 1996 Mar 15; 77: 1144-8.
  1. Fuse H, Muraishi Y, Fujishiro Y, Katayama T. Etoposide, epirubicin and carboplatin in hormone-refractory prostate cancer. Int Urol Nephrol 1996; 28(1): 79-85.
  1. Reviewers' consensus on the use of etoposide for the treatment of hormone-refractory prostate cancer (HRPC) evidence table, 8/28/00.
  1. Reviewers' consensus on the use of paclitaxel, carboplatin, and etoposide for the treatment of carcinoma of unknown primary site (CUPS) evidence table, 10/25/00.
  1. Greco FA, Erland JB, Patton JF, et al. Carcinoma of Unknown Primary Site (CUPS): Long-term follow-up after taxane-based chemotherapy. Proc ASCO 2000: [Abst 2279A].
  1. Lastra E, Muñoz A, Rubio I, et al. Paclitaxel, carboplatin and oral etoposide in the treatment of patients with CUPS. Proc ASCO 2000: [Abst 2279C].
  1. Hainsworth JD, Erland JB, Thomas M, et al. Treatment of CUPS with paclitaxel, carboplatin, and etoposide: a Minnie Pearl Cancer Research Network phase II trial. Proc ASCO 1997; 16: [Abst 975].
  1. Hainsworth JD, Erland JB, Kalman LA, et al. CUPS: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. J Clin Oncol 1997 Jun; 15(6): 2385-93.
  1. Hainsworth JD, Greco FA. Adenocarcinoma of unknown primary site. http://www.medscape.com/UpToDate/2000/11.00/utd1101.07.hain/utd1101.07.hain-01.html.
Hide
(web2)