Carboplatin

Carboplatin is an alkylating agent that covalently binds to DNA. It modifies the cell cycle by interfering with DNA structure and function. Carboplatin is indicated for the initial treatment of advanced ovarian carcinoma of epithelial origin in combination with other approved chemotherapeutic agents and for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy.

Carboplatin is administered as a 15-60 minute IV infusion. The dosage is determined based on renal function, prior treatment, and performance status. Needles or IV sets containing aluminum parts should not be used (aluminum reacts with carboplatin causing precipitate formation and loss of potency).

• Advanced ovarian carcinoma (epithelial) - initial treatment
• Recurrent ovarian carcinoma - palliative treatment
• Small cell lung cancer

Adults (previously untreated, normal renal function): 400 mg/m² IV infusion (15-60 min), not more frequently than every 4 weeks.

Previously treated patients (single agent): 360 mg/m² IV.

With cyclophosphamide (previously untreated): 300 mg/m² IV.

Renal impairment (CrCl):
CrCl >40 mL/min: 400 mg/m²
CrCl 20-39 mL/min: 250 mg/m²

Risk factors (prior myelosuppressive treatment, low performance status): Initial dose reduced by 20-25% (300-320 mg/m²).

Elderly (≥65 years): Dose adjustment may be necessary based on physical condition.

Children (Solid tumor): 300-600 mg/m² IV every 4 weeks.
Children (Sarcoma): 400 mg/m²/day for 2 days every 21 days.
Children (Brain tumor): 175 mg/m² weekly x 4 weeks with 2 weeks recovery.

Hematologic nadir: Repeat when WBC ≥2000/mm³ and platelets ≥100,000/mm³.

Hepatic impairment: Dose adjustment may not be necessary (not studied).

Hematologic (dose-limiting): Thrombocytopenia (platelets <50,000/mm³ - 25%), neutropenia (granulocytes <1,000/mm³ - 18%), leukopenia (WBC <2,000/mm³ - 14%), anemia (Hb <11 g/dL - 71%). Nadir: Days 14-21; recovery within 35-42 days.

Nephrotoxicity: Elevated serum creatinine (6%), BUN (14%), uric acid (5%); electrolyte decreases (Na 29%, K 20%, Ca 22%, Mg 29%).

Gastrointestinal: Vomiting (65%, 1/3 severe), nausea (15%), abdominal pain (17%), diarrhea (6%), constipation (6%), anorexia.

Allergic (<2%): Erythematous rash, fever, pruritus, urticaria; rarely bronchospasm, hypotension.

Hepatic: Elevated total bilirubin (5%), SGOT (15%), alkaline phosphatase (24%) - generally mild and reversible.

Neurotoxicity: Peripheral neuropathy (4%), paresthesias, decreased deep tendon reflexes (more in cisplatin-pretreated patients).

Other: Fatigue, stomatitis, peripheral neuropathy (tingling and numbness of hands and feet).

Infectious (4%) and hemorrhagic (5%) complications reported.

• Carboplatin should be administered under the supervision of a qualified physician experienced in cancer chemotherapy.
• Monitor peripheral blood counts, renal and hepatic function tests regularly.
• Weekly CBC recommended to assess hematologic nadir for subsequent dose adjustment.
• Perform neurologic evaluations regularly.
• Discontinue if abnormal bone marrow depression, renal or hepatic function occurs.
• Carboplatin myelosuppression is related to renal clearance; carefully assess renal function.
• Carboplatin courses should not be repeated more frequently than monthly.
• Avoid combination with aminoglycosides or other nephrotoxic compounds.
• Allergic reactions (within 5 minutes of administration) should be managed with supportive therapy.
• Do not use during pregnancy and lactation (Category D).

• Pre-existing severe renal impairment (unless benefits outweigh risks)
• Severely myelosuppressed patients
• History of severe allergic reactions to carboplatin, other platinum compounds, or mannitol
• Bleeding tumors
• Pregnancy and lactation

• Aminoglycosides: Increased risk of ototoxicity.
• Nephrotoxic compounds: May potentiate renal toxicity.
• Other myelosuppressive drugs: Additive myelosuppressive effects (carefully plan dosages and timing).
• Do not use aluminum-containing needles or IV sets (aluminum reacts with carboplatin causing precipitate and loss of potency).