Carboplatin

Uses

Initial Treatment of Advanced Ovarian Carcinoma: Carboplatin is used for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimenconsists of Carboplatin and cyclophosphamide. Two randomizedcontrolled studies conducted by the NCIC and SWOG with carboplatin versus cisplatin, both in combination with cyclophosphamide, have demonstrated equivalent overall survival between the two groups.

There is limited statistical power to demonstrate equivalence in overal pathologic complete response rates and long-term survival ( ≥ 3 years) because of the small number of patients with these outcomes: the small number of patients with residual tumor < 2 cm after initial surgery also limits the statistical power to demonstrate equivalence in this subgroup.

Secondary Treatment of Advanced Ovarian Carcinoma: Carboplatin is used for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.

Within the group of patients previously treated with cisplatin, those who have developed progressive disease while receiving cisplatin therapy may have a decreased response rate.

Carboplatin is also used to associated treatment for these conditions: Advanced Cervical Cancer, Advanced Endometrial Cancer, Advanced Esophageal Cancers, Advanced Head and Neck Cancer, Advanced Melanoma, Advanced Non Small Cell Lung Cancer, Advanced Ovarian Carcinoma, Advanced Sarcoma, Metastatic Breast Cancer, Neuroendocrine Carcinoma of the Skin, Pleural mesothelioma malignant, Refractory Hodgkin Lymphoma, Retinoblastoma, Advanced Bladder cancer, Advanced Small cell lung cancer, Advanced Testicular cancer, Advanced Thymoma, Advanced thymic carcinoma, Refractory Non-Hodgkin's lymphoma, Conditioning regimens for allogeneic stem cell transplantation therapy

How Carboplatin works

Carboplatin predominantly acts by attaching alkyl groups to the nucleotides, leading to the formation of monoadducts, and DNA fragmenting when repair enzymes attempt to correct the error. 2% of carboplatin's activity comes from DNA cross-linking from a base on one strand to a base on another, preventing DNA strands from separating for synthesis or transcription. Finally, carboplatin can induce a number of different mutations.

Dosage

Carboplatin dosage

Previously untreated patients: 400 mg/m2 as single short term IV infusion over 15-60 min. Therapy should not be repeated until 4 wk after the previous course and/or until the neutrophil count is at least 2,000 cells/mm3 and the platelet count is at least 100,000 cells/mm3.

Patients previously treated with myelosuppresive therapy or patients with poor performance status: Reduce initial dosage by 20-25% (300-320 mg/m2).

150 mg injection should be reconstituted with 15 ml of sodium chloride solution (0.9%) or water for injection.

450 mg injection should be reconstituted with 45 ml of sodium chloride solution (0.9%) or water for injection.

The reconstituted solution should be diluted by 300 ml (for 150 mg) & 900 ml (for 450 mg) of 5% glucose for injection or 0.9% sodium chloride solution for infusition.

Side Effects

Bone marrow suppression, gastrointestinal effects, nephrotoxicity, nervous system, ototoxicity, allergic reactions, alopecia, mucositis.

Toxicity

Patients experiencing an overdose of carboplatin may present with pronounced neutropenia and hepatotoxicity. Treat patients with symptomatic and supportive measures, which may include delaying their next treatment.

Precaution

Much less renal toxicity than cisplatin so no need for a vigorousm hydration schedule or forced diuresis. If AUC dosing is not used, dose should be reduced to 250 mg/m2 for creatinine clearance of 41 to 59 ml/min and to 200 mg/m2 for clearance of 16 to 40 ml/min. Corticosteroids & antihistamines are employed to alleviate symptoms.

Interaction

Administration of a liver vaccine may be dangerous during treatment with carboplatin. The renal effects of nephrotoxic compounds may be potentiated by carboplatin.

Food Interaction

• Avoid echinacea. Co-administration may decrease effectiveness of immunosuppressants.

Carboplatin Drug Interaction

Moderate: pegfilgrastim, pegfilgrastim, paclitaxel, paclitaxel, docetaxel, docetaxelUnknown: diphenhydramine, diphenhydramine, prochlorperazine, prochlorperazine, dexamethasone, dexamethasone, trastuzumab, trastuzumab, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol, ondansetron, ondansetron

Carboplatin Disease Interaction

Major: infections, bleeding disorders, myelosuppression, renal dysfunctionMinor: peripheral neuropathy

Volume of Distribution

The apparent volume of distribution after a 30 minute intravenous infusion of 300-500 mg/m² was 16 L.

Elimination Route

The C_max and AUC of carboplatin increase proportionally with increasing doses. A 75 mg/m^{2 A 450 mg/m2}

Half Life

The distribution half life of carboplatin is 1.1-2 hours, and the elimination half life was2.6-5.9 hours.

Clearance

The total body clearance after a 30 minute intravenous infusion of 300-500 mg/m² was 4.4 L/h.

Elimination Route

Carboplatin is 65% eliminated in the urine within 12 hours, and 71% eliminated within 24 hours. An additional 3-5% is eliminated in urine from 24 hours to 96 hours. Biliary elimination has not been determined. Carboplatin is predominantly eliminated as the unchanged parent compound.

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk

Contraindication

Carboplatin injection should not be employed in patients with severe bone marrow depression or significant bleeding. It is contraindicated in patients with a history of severe allergic reactions to cisplatin or other platinum containing compounds.

Special Warning

Renal Impairment:

• CrCl (16-40 ml/min)- 200 mg/m2.
• CrCl (41-59 ml/min)- 250 mg/m2.

Storage Condition

Store at 25° C. Protect from light.

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