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Carboplatin (Systemic)


VA CLASSIFICATION
Primary: AN900

Commonly used brand name(s): Paraplatin; Paraplatin-AQ.

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

Carcinoma, ovarian, epithelial (treatment)—Carboplatin is indicated for palliative treatment of epithelial ovarian carcinoma refractory to standard chemotherapy that did or did not include cisplatin{01}{08}. It is also indicated for initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents{01}.
—Carboplatin is indicated, in combination with paclitaxel, for the [ treatment of fallopian tube and peritoneal carcinomas, of ovarian origin]1{96}{97}{98}{99}{100}{101}{102}{103}{104}{105}{106}{107}{108}.

[Carcinoma, breast (treatment adjunct) ]1—Carboplatin is indicated for use in combination with a high-dose chemotherapy regimen (e.g., STAMP-V regimen) at some point in the treatment of breast carcinomas.{33}

[Carcinoma, bladder (treatment)]1—Carboplatin is indicated for use in combination with other chemotherapeutic agents at some point in the treatment of advanced transitional-cell bladder (urothelial) carcinoma. Carboplatin can be a less toxic alternative for patients for whom cisplatin is not an option.{54}{55}{56}{57}{58}{59}{60}{61}{62}{63}{64}{65}{66}{67}{68}{69}{70}

[Carcinoma, endometrial (treatment) ]1—Carboplatin is indicated as reasonable medical therapy in the treatment of endometrial carcinoma{15}{16}{17}{18}{19}. (Evidence rating: IIID)

[Carcinoma, esophageal (treatment) ]1—Carboplatin is indicated for use in combination with paclitaxel at some point in the treatment of esophageal carcinoma and adenocarcinoma. Carboplatin is a reasonable substitution for cisplatin.{71}{72}{73}{74}{75}{76}{77}{78}{79}

[Carcinoma, lung, small cell (treatment) ]1
[Carcinoma, lung, non–small cell (treatment)]1
[Carcinoma, head and neck (treatment) ]1
[Carcinoma, testicular (treatment) ]1 or
[Seminoma (treatment)]1—Carboplatin is indicated for treatment of small cell{07} and non–small cell{12} lung carcinoma, head and neck tumors{07}, nonseminomatous testicular carcinoma{11}{12}, and seminoma{07}.

[Carcinoma, unknown primary site (treatment )]1—Carboplatin is indicated for the first-line treatment of carcinoma of unknown primary site (CUPS), as part of a combination regimen with paclitaxel and etoposide. 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.{80}{81}{82}{83}{84}{85}

[Retinoblastoma (treatment)]1—Carboplatin is indicated as reasonable medical therapy in the treatment of retinoblastoma{20}{21}{22}{23}{24}{25}{26}{27}{28}{29}{30}{31}. (Evidence rating: IIID)

[Tumors, brain, primary (treatment) ]1—Carboplatin is indicated for treatment of primary brain tumors{13}{14}.

[Lymphomas, Hodgkin's (treatment) ]1
[Lymphomas, non-Hodgkin's (treatment) ]1—Carboplatin is indicated, in combination with ifosfamide and etoposide (ICE regimen), for the treatment of Hodgkin's and non-Hodgkin's lymphomas.{117}{118}{119}{120}{121}{122}{123}{124}{125}{126}{127}{128}{129}{130}{131}{132}{133}{134}

[Malignant melanoma (treatment)]1—Carboplatin is indicated for treatment of malignant melanoma{13}{14}.

Acceptance not established
Use of carboplatin for the treatment of cervical carcinoma has not been established.{34}{35}{36}{37}{38}{39}{40}{41}{42}{43}{44}{45}{46}{47}{48}{49}{50}{51}{52}{53}

Use of carboplatin for the treatment of merkle cell carcinoma has not been established. Even though this is a rare tumor, more data is needed showing single-agent activity or contribution when added to combination therapy.{157}{158}{159}{160}{161}{162}{163}{164}

Unaccepted
Carboplatin is not indicated for the treatment of gastric carcinomas, due to lack of efficacy as a single agent and having an undefined role in combination therapy.{86}{87}{88}{89}{90}{91}{92}{93}{94}{95}

Carboplatin is not indicated as single-agent therapy for the 2nd- or 3rd-line treatment of breast carcinoma.{109}{110}{111}{112}{113}{114}{115}{116}

Note: The USP medical experts chose to not include carboplatin as single-agent therapy for the 1st-line treatment of breast carcinoma.{109}{110}{111}{112}{113}{114}{115}{116}
The USP medical experts chose to not include carboplatin for the treatment of hormone-refractory prostate cancer (HRPC). There is not enough medical literature or clinical experience to consider this indication.{135}{136}{137}{138}{139}{140}{141}{142}{143}
The USP medical experts chose to not include carboplatin for the treatment of acute leukemias, as a single agent{144}{145}{146}{147}{148}{149}{150} or in combination therapy{144}{146}{151}{152}{153}{154}{155}{156}. There is insufficient information offering evidence of increased activity or reduced toxicity over standard agents.{150}{156}

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    371.26

Mechanism of action/Effect:

Carboplatin resembles an alkylating agent. Although the exact mechanism of action is unknown, action is thought to be similar to that of the bifunctional alkylating agents, that is, possible cross-linking and interference with the function of DNA {01} {03} {04}. It is cell cycle–phase nonspecific {01}.

Protein binding:

Very low {03} {04}; however, platinum from carboplatin is irreversibly bound to plasma proteins {01} {04} and is slowly eliminated with a minimum half-life of 5 days {01}.

Biotransformation:

By hydrolysis in solution (aquation), at a rate slower than occurs with cisplatin, to the active species that reacts with DNA {01} {04}.

Half-life:

Alpha phase—1.1 to 2 hours {01}.

Beta phase—2.6 to 5.9 hours {01}.

Elimination:
    Renal (71% within 24 hours {01} {04} at creatinine clearances of 60 mL per minute and greater {01}).


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to cisplatin or other platinum-containing compounds may be sensitive to carboplatin also {01}.

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 effect of dose and duration of therapy is 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.

Mutagenicity

Both in vivo and in vitro studies have shown carboplatin to be mutagenic {01}.

Pregnancy/Reproduction
Fertility—
Gonadal suppression, resulting in amenorrhea or azoospermia, may occur in patients taking 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—
Carboplatin is embryotoxic and teratogenic in rats {01}.

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.

FDA Pregnancy Category D.

Breast-feeding

Although very little information is available regarding distribution of antineoplastic agents into breast milk, breast-feeding is not recommended while carboplatin is being administered because of the risks to the infant (adverse effects, mutagenicity, carcinogenicity). It is not known whether carboplatin is distributed into breast milk {01}.

Pediatrics

No information is available on the relationship of age to the effects of carboplatin in pediatric patients.


Geriatrics


Incidence of peripheral neurotoxicity is increased {01} and myelotoxicity may be more severe {04} {08} in patients older than 65 years of age. In addition, elderly patients are more likely to have age-related renal function impairment, which may require dosage reduction and careful monitoring of blood counts in patients receiving carboplatin.


Dental

The bone marrow depressant effects of carboplatin 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.

Carboplatin rarely may also cause mucositis or stomatitis 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 carboplatin may be increased with concurrent or recent therapy if these medications cause the same effects; dosage adjustment of carboplatin, if necessary, should be based on blood counts )


» Bone marrow depressants, other {01} (see Appendix II ) or
Radiation therapy {01}    (concurrent use may increase the total effects of these medications and radiation therapy; dosage reduction is recommended)

{01}
Cisplatin    (incidence of carboplatin-induced neurotoxicity {01} {08} or ototoxicity {08} is increased in patients previously treated with cisplatin {01} {08}; use of carboplatin worsens pre-existing cisplatin-induced neurotoxicity [in about 30% of those patients] {01} or ototoxicity {08}; additive nephrotoxicity has not been reported {03})


Nephrotoxic medications, other {01} (see Appendix II ) or
Ototoxic medications, other {02} (see Appendix II )    (concurrent and/or sequential administration may increase the potential for ototoxicity and nephrotoxicity)


Vaccines, killed virus    (because normal defense mechanisms may be suppressed by carboplatin 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 carboplatin 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 patient's antibody response to the vaccine; immunization of these patients should be undertaken only with extreme caution after careful review of the patient's hematologic status and only with the knowledge and consent of the physician managing the carboplatin therapy. 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. In addition, immunization with oral poliovirus vaccine should be postponed in persons in close contact with the patient, especially family members)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Bilirubin {01} concentrations, serum and
Alkaline phosphatase {01} values, serum and
Aspartate aminotransferase (AST [SGOT]) {01} values, serum    (may be increased; increases are usually mild and are reversible in 50% of cases {01}; severe abnormalities occur at carboplatin doses of more than four times the recommended dose {01})


Blood urea nitrogen (BUN) concentrations {01} and
Creatinine concentrations, serum {01}    (may be increased, indicating nephrotoxicity; usually mild {01}; reversible in about 50% of cases {01})


Calcium {01} and
Magnesium {01} and
Potassium {01} and
Sodium {01}    (serum concentrations may be decreased)


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
Ascites or
Pleural effusion    (increased risk of toxicity {03})


Bleeding, significant {01}
» Bone marrow depression {01}
» Chickenpox, existing or recent (including recent exposure) or
» Herpes zoster    (risk of severe generalized disease {06})


Hearing impairment {07}
» Infection
» Renal function impairment    (reduced elimination; increased bone marrow depression {01}; incidence and severity of nephrotoxicity may be increased {08}. A lower dosage of carboplatin is recommended in patients with impaired renal function {01} {04} and careful monitoring of blood counts between courses is recommended {01})


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

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Audiometric testing    (recommended prior to initiation of therapy and if ototoxicity is suspected during therapy {07})


Blood urea nitrogen (BUN) concentrations and
» Creatinine clearance {01} and
Creatinine concentrations, serum    (recommended prior to initiation of therapy and before each course of carboplatin to adjust dosage and detect renal toxicity {01} {08})


Calcium concentrations, serum and
Magnesium concentrations, serum and
Potassium concentrations, serum and
Sodium concentrations, serum    (recommended at periodic intervals during therapy)


» 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 {08}; frequency varies according to clinical state, agent, dose, and other agents being used concurrently)


Neurologic function studies {08}    (recommended prior to initiation of therapy and at periodic intervals during therapy)




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) are actually used as parameters to aid in individual dosage titration.
Carboplatin infrequently causes mild renal toxicity, which may be detected initially only by means of renal function tests {03}.

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
—dose-related     
Anemia {01} {08} (unusual tiredness or weakness)—usually asymptomatic
    
leukopenia or neutropenia {01} {08} (fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)— usually asymptomatic
    
pain at site of injection {01} {03}
    
thrombocytopenia {01} {08} (unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)— usually asymptomatic

Note: Anemia may be cumulative {01}; transfusions are frequently necessary {01} {03} {09}.
With leukopenia and thrombocytopenia, nadir of leukocyte and platelet counts occurs after 21 days {01} and counts usually recover by 30 days after a dose {03}. Nadir of granulocyte counts usually occurs after 21 to 28 days and counts usually recover by day 35 {03}.
Leukopenia and thrombocytopenia are dose-dependent and cumulative {01} {05}; in a small percentage of patients (less than 10%) they are unpredictable {05}.


Incidence less frequent
    
Allergic reaction {01} (skin rash or itching; wheezing)
    
peripheral neurotoxicity {01} {04} {08} (numbness or tingling in fingers or toes)
    
ototoxicity {01}{03}(ringing in ears)— usually asymptomatic

Note: An allergic reaction occurs within minutes of administration {01}.
Neurotoxicity may be cumulative {01}.
With ototoxicity, hearing loss usually occurs first with high frequencies (above speech tones) {08} and may be unilateral or bilateral {10}.


Incidence rare
    
Blurred vision {01}
    
mucositis {01} or stomatitis {04} (sores in mouth and on lips)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Asthenia {01} (unusual tiredness or weakness)
    
nausea and vomiting

Note: Less frequently, asthenia may be related to anemia.
Nausea and vomiting occur in about 65% of patients; these are severe in about one third of those {01}. Nausea alone occurs in about 10 to 15% of patients {01}. Symptoms usually begin 6 to 12 hours after a dose, and vomiting may persist for 24 hours {04}. May be treated or prevented by antiemetic medication {01} {08}.


Incidence less frequent
    
Constipation or diarrhea {01} {03} {08}
    
loss of appetite {01} {04}



Those not indicating need for medical attention
Incidence less frequent
    
Loss of hair {01} {03}





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

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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to cisplatin or other platinum-containing compounds, or to carboplatin

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 the elderly—Increased incidence of peripheral neurotoxicity and severity of myelotoxicity
Other medications, especially other bone marrow depressants or previous cytotoxic drug or radiation therapy
Other medical problems, especially chickenpox, herpes zoster, other infections, or renal function impairment

Proper use of this medication
Caution if taking combination therapy; taking each medication at the right time

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

» Proper dosing

Precautions while using this medication
» Importance of close monitoring by the 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 within the past several months 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 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 might occur


Side/adverse effects
May cause adverse effects such as ear and kidney problems, blood problems, and cancer; importance of discussing possible effects with physician

Signs of potential side effects, especially anemia, leukopenia or neutropenia, pain at site of injection, thrombocytopenia, allergic reaction, peripheral neurotoxicity, ototoxicity, blurred vision, and mucositis or stomatitis

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
It is recommended that carboplatin be administered to patients under supervision of a physician experienced in cancer chemotherapy {01}. It is also recommended that equipment and medications (including epinephrine, oxygen, antihistamines, and intravenous corticosteroids) necessary for treatment of a possible anaphylactic reaction be readily available at each administration of carboplatin {01}.

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

Carboplatin 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.

It is recommended that carboplatin be administered as an intravenous infusion, usually over 15 to 60 minutes {01} {08}. No pre- or post-treatment hydration or forced diuresis is required {01}.

Carboplatin has also been administered as a continuous intravenous infusion over 24 hours or by dividing the total dose into five consecutive daily pulse doses; this method of administration appears to reduce nausea and vomiting {01} but not nephrotoxicity or ototoxicity {03}.

It is recommended that courses of carboplatin be administered no more frequently than every 4 weeks {03} {08} to allow recovery of bone marrow {03}.

Administration of subsequent doses of carboplatin is not recommended before platelet levels return to at least 100,000 per cubic millimeter and leukocyte levels to at least 2000 per cubic millimeter {01}.

Special precautions are recommended in patients who develop thrombocytopenia as a result of administration of carboplatin. 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.

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.


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.


Note: The Calvert formula has been widely used to individualize carboplatin dosing and it permits targeting at an acceptable level of toxicity, based on the individual patient's renal function.


Total Dose (mg) = (target AUC [mg per mL x min]) × (GFR [mL per minute] + 25). AUC (area under the plasma concentration–time curve) and GFR (glomerular filtration rate) are used.{134}


CARBOPLATIN FOR INJECTION

Usual adult dose
Carcinoma, ovarian, epithelial
Initial: Intravenous, according to the formula,


Total dose (mg) = (target AUC) × (GFR + 25) where AUC (area under the plasma concentration-time curve) is expressed in mg per mL x min and GFR (glomerular filtration rate) is expressed in mL per minute{01}{32}.

The target AUC of 4 to 6 mg per mL x min using carboplatin monotherapy appears to provide the most appropriate dose range in previously treated patients{01}.
Additional dosing option: Advanced, initial treatment—Intravenous, 300 mg per square meter of body surface area once every four weeks (day 1) for six cycles, in combination with cyclophosphamide 600 mg per square meter of body surface area intravenously once every four weeks (day 1) for six cycles{01}.

Refractory to other chemotherapy: Intravenous, 360 mg per square meter of body surface area once every four weeks (day 1){01}.
Note: An initial dose of 250 mg per square meter of body surface area is recommended in patients with creatinine clearance of 41 to 59 mL per minute; an initial dose of 200 mg per square meter of body surface area is recommended in patients with creatinine clearance of 16 to 40 mL per minute.{01}

A suggested dosage adjustment schedule for subsequent doses is{01}:

Nadir after prior dose
(cells per cubic millimeter)
% of Prior dose
to be given
Neutrophils
Platelets
 
>2000
>100,000
125
500–2000
50,000–100,000
100
<500
<50,000
75

Note: Only one dose escalation should be made{01}.
Geriatric patients may require lower doses{04}.


For the [treatment of fallopian tube and peritoneal carcinomas of ovarian origin]1, patients have benefited from intravenous doses of carboplatin AUC 5 to 6 mg per mL x min, in combination with paclitaxel 135 to 175 mg/m 2 (by 3–hour infusion), every 21 days, for 5 to 9 treatment cycles. Duration of paclitaxel infusion may be adjusted from 1 hour to 24 hours, depending on toxicity.{108}

[Carcinoma, bladder]1 or
[ Carcinoma, breast]1 or
[Carcinoma, endometrial]1 or
[Carcinoma, head and neck]1or
[Carcinoma, lung, non-small cell]1 or
[Carcinoma, lung, small cell]1 or
[Malignant melanoma]1or
[Retinoblastoma ]1 or
[Seminoma]1 or
[Tumors, brain, primary]1
Consult medical literature or manufacturer's literature for information on dosage.

[Carcinoma, esophageal]1
Patients have benefited from intravenous doses of AUC 5 to 6 mg per mL x min, for up to 6 treatment cycles.{71}

[Carcinoma, unknown primary site ]1
Patients have benefited from an intravenous dose of AUC 6 mg per mL x min , on day 1 of a 21–day treatment cycle, combined with intravenous paclitaxel and oral etoposide, for 4 to 8 cycles.{80}

[Lymphomas, Hodgkin's]1or
[ Lymphomas, non-Hodgkin's]1
As part of the ICE regimen (i.e., ifosfamide and etoposide), patients have benefited from intravenous doses of 750 to 1800 mg/m 2 (total dose). Using the Calvert formula, an intravenous dose of AUC 5 mg per mL x min (maximum 800 mg), every 14 days, for 3 cycles has provided benefit.{117}


Usual pediatric dose
Dosage has not been established.

Size(s) usually available:
U.S.—


50 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]


150 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]


450 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]

Canada—


50 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]


150 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]


450 mg (Rx) [Paraplatin (mannitol, equal quantity by weight)]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light.

Preparation of dosage form:
Carboplatin for injection is reconstituted for intravenous use by adding 5, 15, or 45 mL of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection to the 50-mg, 150-mg, or 450-mg vial, respectively, producing a solution containing 10 mg of carboplatin per mL. The resulting solution may be further diluted to a concentration as low as 500 mcg (0.5 mg) per mL with 5% dextrose injection or 0.9% sodium chloride injection if further dilution for administration by intravenous infusion is required.

Stability:
Reconstituted solutions of carboplatin are stable for 8 hours at 25 °C (77 °F).

Caution—A black platinum precipitate will form if carboplatin comes in contact with aluminum.

Incompatibilities:
Do not use needles, intravenous sets, or equipment containing aluminum for administration since carboplatin is incompatible with aluminum.


CARBOPLATIN INJECTION

Usual adult dose
See Carboplatin for injection.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


10 mg per mL (Rx) [Paraplatin-AQ]

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

Stability:
Caution—A black platinum precipitate will form if carboplatin comes in contact with aluminum.

Incompatibilities:
Do not use needles, intravenous sets, or equipment containing aluminum for administration since carboplatin is incompatible with aluminum.



Developed: 09/02/1999
Revised: 12/12/2002



References

Note: References used in the development and subsequent revisions of this monograph have not been incorporated into the database and therefore are not listed below.

  1. Paraplatin package insert (Bristol—US), Rev 7/91; Rev 12/96, Rec 6/98.
  1. Canetta R, Gragman K, Smaldone L, et al. Carboplatin: current status and future prospects. Cancer Treat Rev 1988; 15 (Suppl B): 17-32.
  1. Woloschuk DMM, Pruemer JM, Cluxton RJ. Carboplatin: a new cisplatin analog. Drug Intell Clin Pharm 1988 Nov; 22: 843-9.
  1. Wagstaff AJ, Ward A, Benfield P, et al. Carboplatin. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of cancer. Drugs 1989; 37: 162-90.
  1. Reviewer comment, 1990 revision.
  1. Hematology-oncology panel comments, 1/24/90.
  1. Reviewers' responses to panel ballot, 1990 revision.
  1. Paraplatin and Paraplatin-AQ product monograph (Bristol—Canada), Rev 2/20/87.
  1. Reviewer response, 1991 revision.
  1. Reviewers' responses to panel question #4, 1990 revision.
  1. Reviewers' responses to Hematology-Oncology Advisory Panel (1985-1990) Memorandum No. 26, 8/28/89.
  1. Reviewers' responses to Hematology-Oncology Advisory Panel (1985-1990) Memorandum No. 24, 6/6/89.
  1. DeVita VT, Hellman S, Rosenberg SA. Cancer principles and practice of oncology. 4th ed. Philadelphia: Lippincott; 1993.
  1. Reviewers' responses to Hematologic-Oncologic Disease Advisory Panel Memo #9 of 1/30/97.
  1. Pinelli DM, Fiorica JV, Roberts WS, et al. Chemotherapy plus sequential hormonal therapy for advanced and recurrent endometrial carcinoma. A phase II study. Gynecol Oncol 1996; 60(3): 462-7.
  1. Price FV, Edwards RP, Kelley JL, et al. A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. Semin Oncol 1997; 24(5 Suppl 15): S78-S82.
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  1. Reviewers' consensus on the use of carboplatin for the treatment of gastric carcinomas ballot, 5/31/01.
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  1. Reviewer's consensus on the use of carboplatin for the treatment of Hodgkin's and non-Hodgkin's lymphomas ballot, 7/24/01.
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  1. Reviewers' consensus on the use of carboplatin for the treatment of hormone-refractory prostate cancer (HRPC) evidence table, 8/10/00.
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  1. Reviewers' consensus on the use of carboplatin for the single-agent treatment of acute leukemias ballot, 11/19/01.
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  1. Reviewers' consensus on the use of carboplatin for the treatment of merkle cell carcinoma ballot, 2/26/02.
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