Carboplatin

Therapeutic Class
 Antineoplastic Agent, Alkylating Agent; Antineoplastic Agent, Platinum Analog
Indications

Treatment of advanced ovarian cancer

Unlabeled/Investigational: Treatment of bladder cancer, breast cancer (metastatic), central nervous system tumors, cervical cancer (recurrent or metastatic), endometrial cancer, esophageal cancer, head and neck cancer, Hodgkin's lymphoma (relapsed or refractory), malignant pleural mesothelioma, melanoma (advanced or metastatic), merkel cell carcinoma, neuroendocrine tumors (adrenal gland and carcinoid tumors), non-Hodgkin’s lymphomas (relapsed or refractory), nonsmall cell lung cancer, prostate cancer, sarcomas (Ewing’s sarcoma and osteosarcoma), small-cell lung cancer, testicular cancer, thymic malignancies, unknown primary adenocarcinoma, and as a conditioning regimen prior to hematopoietic stem cell transplantation.
Adult Doses

Intravenous
Advanced ovarian carcinoma
Adult: As a single agent in previously untreated patients: 400 mg/m2. As a single agent in previously treated patients with recurrent disease: 360 mg/m2. When used with cyclophosphamide in previously untreated patients: 300 mg/m2. Doses to be given by IV infusion over 15-60 minutes and not more frequently than every 4 wk. Subsequent doses should be adjusted based on nadir of WBC and platelet counts.

CrCl (ml/min) Dosage Recommendation
≥40 Recommended dose: 400 mg/m2.
20-39 Recommended dose: 250 mg/m2.

The Calvert formula should be used to calculate dosing for elderly patients.
Pediatric Doses

Glioma (unlabeled use) (in combination with vincristine) :
I.V.: 175 mg/m2 weekly for 4 weeks every 6 weeks, with a 2-week recovery period between courses
Sarcomas: Ewing’s sarcoma, osteosarcoma (unlabeled uses) (in combination with ifosfamide and etoposide)
I.V.:400 mg/m2/day for 2 days every 21 days
Doses in Renal impairment

The Calvert formula should be used to calculate dosing.
Doses in Hepatic impairment

Minimal hepatic metabolism; dosage adjustment may not be needed. 
Contraindications

Previous allergy; pregnancy, lactation; allergy to other platinum compounds; severe bone marrow depression; significant bleeding, aluminium containing needles and IV sets.
Boxed Warning

Bone marrow suppression, which may be severe, is dose related.
Anaphylactic-like reactions have been reported with carboplatin; may occur within minutes of administration. Epinephrine, corticosteroids and antihistamines have been used to treat symptoms.
Vomiting may occur.
Should be administered under the supervision of an experienced cancer chemotherapy physician.
Warnings / Precautions

Use appropriate precautions for handling and disposal.
Bone marrow suppression, Hypersensitivity/anaphylactoid reactions, Vomiting.

Neurotoxicity: Peripheral neuropathy occurs infrequently, More chance in patients >65 years of age ( Also severe thrombocytopenia  ) and those who have previously received cisplatin treatment.

Ototoxicity: Clinically significant hearing loss,mostly in pediatric when therapy was administered at higher than recommended doses in combination with other ototoxic agents (eg, aminoglycosides).

Vision loss: Loss of vision (reversible) has been reported with higher than recommended doses.

Renal impairment: patients with renal dysfunction are at increased risk for bone marrow suppression.
Taxane derivatives: taxane derivatives (docetaxel, paclitaxel) should be administered before the platinum derivatives (carboplatin, cisplatin) to limit myelosuppression and to enhance efficacy.
Adverse Reactions

Potentially Fatal: Bone marrow suppression and anaphylactic reactions.

Central nervous system: Pain, Neurotoxicity
Dermatologic: Alopecia
Hematologic: Myelosuppression, anemia, leukopenia, neutropenia, thrombocytopenia, Bleeding, hemorrhagic complications
Gastrointestinal: Vomiting, abdominal pain, nausea, Constipation, diarrhea, stomatitis/mucositis, taste dysgeusia
Endocrine & metabolic: Hyponatremia, hypomagnesemia, hypocalcemia(22% to 31%), hypokalemia
Hepatic: Alkaline phosphatase increased, AST increased, Hepatic: Bilirubin increased
Neuromuscular & skeletal: Weakness, Peripheral neuropathy
Renal: Creatinine clearance decreased, BUN increased
Ocular: Visual disturbance
Otic: Ototoxicity
Miscellaneous: Hypersensitivity/allergic reaction, Infection
Drug Interactions

Increased risk of ototoxicity when used with aminoglycosides.
See Below for More carboplatin Drug Interactions
Food Interactions

Herb/Nutraceutical: Avoid black cohosh, dong quai in estrogen-dependent tumors
Mechanism of Actions

Carboplatin is an alkylating agent which binds covalently to DNA. It modifies the cell cycle by interfering with DNA structure and function.
Pharmacodynamics

Distribution: Vd: 16 L (based on a dose of 300-500 mg/m2); into liver, kidney, skin, and tumor tissue

Protein binding: Carboplatin: 0%; Platinum (from carboplatin): Irreversibly binds to plasma proteins

Metabolism: Minimally hepatic to aquated and hydroxylated compounds

Half-life elimination: Clcr >60 mL/minute: Carboplatin: 2.6-5.9 hours (based on a dose of 300-500 mg/m2); Platinum (from carboplatin): ≥5 days

Excretion: Urine (~70% as carboplatin within 24 hours; 3% to 5% as platinum within 1-4 days)
Monitoring

CBC (with differential and platelet count), serum electrolytes, serum creatinine and BUN, creatinine clearance, liver function tests.
Administration

Usually infused over 15-60 minutes, although some protocols may require infusions up to 24 hours. When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives to limit myelosuppression and to enhance efficacy.

Stable in D51/4NS, D51/2NS, D5NS, D5W, NS.
Pregnancy Category

D: Drug Pregnancy Category There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.
Lactation

Excretion in breast milk unknown/not recommended.
Storage Conditions

Intravenous: Store at 25°C.
ATC Classification
 L01XA02
GenericPedia Classification
    • Storage

    Intravenous: Store at 25°C.
    Available As
  • Carboplatin 10 mg

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