Cisplatin

Indications

Cisplatin is used for: Lymphomas, Sarcomas, Carcinomas, Small cell lung cancer, Ovarian cancer, Germ cell tumors, Metastatic Testicular Tumors, Metastatic Ovarian Tumors, Advanced Bladder Cancer

Adult Dose

Metastatic Testicular Tumors Usual dose in combination with other approved chemotherapeutic agents is 20 mg/m²/day IV for 5 days/cycle Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose May use concomitant amifostine to decrease nephrotoxicity Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³ Advanced Bladder Cancer 50-70 mg/m² IV cycle q3-4Weeks, depending on prior radiation therapy or chemotherapy; for heavily pretreated patients, give 50 mg/m²/cycle initially; repeat q4Weeks Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose May use concomitant amifostine to decrease nephrotoxicity Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³ Metastatic Ovarian Carcinoma 75-100 mg/m² IV per cycle q4Weeks with cyclophosphamide (600 mg/m² IV q4Weeks); administer sequentially Off-label: 90-270 mg/m² intraperitoneal; retain for 4 hr before draining; repeat q3Weeks (may coadminister systemic Na thiosulfate) Pretreatment hydration: 1-2 L fluid infused for 8-12 hr before dose May use concomitant amifostine to decrease nephrotoxicity Do not repeat course until SCr <1.5 mg/dL [<133 micromoles/L] or BUN <25 mg/dL [<8.93 mmol/L] or WBC >4000/mm³ AND platelets >100 k/mm³

Child Dose

Renal Dose

Renal Impairment CrCl 10-50 mL/min: Decrease dose 50% CrCl <10 mL/min: Contraindicated

Administration

IV Preparation Further dilution stability is dependent on chloride ion concentration & should be mixed in solutions of NS (at least 0.3% NaCl) Further dilution in NS, D5/½NS or D5/NS to a concentration of 0.05-2 mg/mL are stable for 72 hr at 4-25°C in combination with mannitol May administer 12.5-50 g mannitol/L Standard dilution: dose/250-1000 mL NS, D5W/NS or D5/½NS IV Administration Perform pretreatment hydration Do not use aluminum-containing needles or IV administration sets that may come in contact with carboplatin (aluminum can react causing precipitate formation & loss of potency) Administration rate has varied from a 15-120 min infusion, 1 mg/min infusion, 6-8 hr infusion, 24 hr infusion, or per protocol Maximum rate of infusion: 1 mg/min in patients with CHF When administered as sequential infusions, taxane derivatives (docetaxel, paclitaxel) should be administered before platinum derivatives to limit myelosuppression & to enhance efficacy

Contra Indications

Patients with severe renal or auditory disorder, known hypersensitivity, severe bone marrow suppression, peripheral neuropathy, pregnancy, lactation.

Precautions

Patients with renal or hepatic disorder, myelosuppression. Monitor renal, neurological and auditory function. Perform blood counts regularly. Maintain adequate hydration before and 24 hr after admin to minimise nephrotoxicity. Lactation: excreted in breast milk; do not nurse

Pregnancy-Lactation

Interactions

Synergistic with 5-fluorouracil and etoposide. Efficacy increased and toxicity reduced when combined with radioprotecting agent WR 2721. At doses ?100 mg, cisplatin is an ideal drug to combine with other cytotoxic drugs; unlike other antineoplastic drugs, it causes little myelosuppression. Potentially Fatal: Potentiates nephrotoxicity with aminoglycosides. Increased toxicity when combined with other cytotoxic drugs.

Adverse Effects

Side effects of Cisplatin : >10% Nausea (76-100%),Vomiting (76-100%),Nephrotoxicity (28-36%),Ototoxicity, especially in children (31%),Myelosuppression (25-30%),Anaphylaxis (1-20%),Alopecia Frequency Not Defined Cerebral herniation,Encephalopathy,Leukoencephalopathy and reversible posterior leukoencephalopathy syndrome,Seizure,Peripheral neuropathy (dose and duration dependent),Diarrhea,Electrolyte changes,Hyperuricemia,Hepatotoxicity,Local tissue irritation Potentially Fatal: Rarely, renal damage due to inadequate hydration during therapy. Very rarely life-threatening myelosuppression. Anaphylactoid reactions (rare) and cardiac abnormalities.

Mechanism of Action

Cisplatin modifies cell cycle by interfering with DNA structure and function. Effects are most prominent during the S phase but cells are killed at all stages. Cisplatin synergises with other anticancer drugs e.g. fluorouracil. It has a narrow therapeutic margin and is highly toxic.