Cisplatin
Common Brand Names: Platinol
Therapeutic Class: Antineoplastic, Alkylating agent
Common Injectable Dosage Forms:
Solution for Injection: 1 mg/mL in 50 mL, 100 mL, 200 mL vials
Dosage Ranges:
Treatment of bladder cancer: 50-70 mg/m2 IV as a single dose once every 3-4 weeks in combination with other antineoplastic agents.
Malignant mesothelioma: 75 mg/m2 over 2 hours with pemetrexed over 10 minutes on day 1 of 21-day cycle. Give cisplatin 30 minutes after end of pemetrexed infusion.
Treatment of ovarian cancer: 50-75 mg/m2 once every 21 days in combination with cyclophosphamide or paclitaxel.
Treatment of testicular cancer: 60 mg/m2 as a single dose on days 23 of a 60-day regimen with other antineoplastic agents.
Dosing varies from protocol to protocol, and dose greater than 100 mg/m2 should be confirmed with prescriber. No adjustment necessary in hepatic impairment, dosage adjustment necessary if CrCl <50 mL/min.
Administration and Stability: Administer cisplatin IV or intra-arterially. Adequate renal function should be established prior to administration. Hydrate with 250 mL/hour NS 2-4 hours before and after cisplatin to ensure adequate hydration. Premedicate with antiemetics including serotonin antagonists and a corticosteroid to prevent severe nausea and vomiting. Do not use aluminum needles or IV sets. Cisplatin injection should be diluted in NS to a final concentration of 50-500 mg/L. Admixture is stable up to 24 hours at room temperature. Infuse cisplatin over 6-8 hours, no faster than 1 mg/min. PH 3.9-5
Pharmacology/Pharmacokinetics: Cisplatin binds with DNA to form intrastrand crosslinks that cause changes in conformation of DNA, which affects DNA replication. Cisplatin enters cells by passive diffusion, where it undergoes transformation and binds specifically to the N-7 position of guanine and adenine, which changes the DNA and RNA polymerases, as well as RNA translocation and other key enzymes. Cisplatin also causes mitochondrial damage, decreased ATPase activity, and altered cellular transport mechanisms. Cisplatin causes cell cycle disruption at G2 phase, which induces cell death. It is distributed widely throughout the body tissues, with higher concentrations in prostate, liver, and kidneys. Elimination is triphasic, initial phase lasts about 20 minutes, second phase about 48-70 minutes, and the terminal phase is about 24 hours. 23-75% of dose is eliminated in the first 24 hours, while traces of drug may be found in urine up to 6 months following discontinuation of therapy.
Drug and Lab Interactions: Other nephrotoxic drugs can increase renal toxicity and electrolyte loss. Aminoglycosides, amphotericin C, cyclosporin, loop diuretics, and vancomycin should be used cautiously during cisplatin treatment. Cisplatin may decrease renal clearance of some chemotherapy drugs and dose reductions may be necessary when used concomitantly.
Contraindications/Precautions: Contraindicated in patients with known hypersensitivity to cisplatin or other platinum-containing compounds. Cisplatin should be used with caution in patients with preexisting renal insufficiency, myelosuppression, hearing impairment, and in pregnancy. Elderly patients are more susceptible to nephrotoxicity and peripheral neuropathy and should be monitored closely.
Monitoring Parameters: BUN, Cr, CrCl, electrolytes before and within 48 hours after dose, audiography, neurologic exam, liver function tests periodically, CBC with differential, urine output.
Adverse Effects: Acute renal failure (azotemia, increase serum Cr, electrolyte abnormalities) is possible. Inadequate hydration and concomitant aminoglycosides use are the most important risk factors for renal toxicity. Other possible adverse effects include hearing loss, neurotoxicity, blurred vision, hiccups, increased LFTs, and alopecia. Anaphylactoid reactions may occur, usually in patients with prior to platinum and/or more than 6 months of cisplatin therapy.
Common Clinical Applications: Cisplatin is used in the treatment of bladder, testicular, and ovarian cancers.
