Drug type
• A platinum-containing, alkylating agent
• Often used in combination with other chemotherapy agents as well as monotherapy because of its relative lack of hematologic toxicity
Indications
• Invasive bladder malignancy
• Ovarian carcinoma
• Ovarian germ cell tumor carcinoma
• Testicular germ cell tumor
Unlabeled uses
• Adrenal cortex carcinoma
• Conditioning prior to allogeneic hematopoietic stem cell transplantation
• Endometrial carcinoma
• Gastric cancer
• Malignant tumor of cervix
• Malignant tumor of head and neck
• Metastatic breast carcinoma
• Metastatic malignant tumor of anus
• Multiple myeloma
• Neuroblastoma
• Neuroendocrine prostate carcinoma
• Osteosarcoma of bone
• Pancreatic carcinoma
• Progressive diffuse large B-cell lymphoma
• Small cell lung carcinoma and non-small cell lung cancer (NSCLC)
Mechanism of action
• Cell cycle nonspecific
• Complete mechanism of action is not entirely understood
• Appears to inhibit DNA synthesis by binding to DNA and disrupting its function
• Also enhances tumor immunogenicity
Dosage and administration
• Inadvertent substitution of cisplatin for carboplatin can result in potentially fatal overdose.
• Any dose >100 mg/m2 should be verified
• Cisplatin is administered by IV infusion
—Also intra-arterial injection and intraperitoneal injection
• Dose
—Minimum: 25.95 mg/1.73 m2
—Maximum: 173.0 mg/1.73 m2
• For optimum therapeutic results with minimum adverse effects, base dosage on clinical, renal, hematologic, and otic response and patient tolerance
• Consult published protocols for dosage, method, and sequence of administration
• At the usual dosage, do not give courses of therapy more frequently than once every 3-4 weeks
• Patients should be adequately hydrated before and for 24 hours after administration to ensure good urinary output and minimize nephrotoxicity.
• Needles, syringes, catheters, or IV administration sets containing aluminum parts that may come in contact with cisplatin should not be used for preparation or administration.
Pregnancy and lactation
• Pregnancy category D
—Cisplatin may cause fetal harm when administered to a pregnant woman.
• Lactation
—Absolute contraindication
Cautions and adverse effects
• Cautions
—Pediatric: Relative contraindication: risk of severe ototoxicity in children.
—Geriatric: Increased risk of kidney, neurologic, hematologic toxicities; may need to reduce dose
• Adverse effects
—Most frequent: Peripheral neuropathy (dose and duration dependent); bone marrow depression: anemia, leucopenia; hemolytic anemia, thrombocytopenic disorder; hyperuricemia; hypomagnesemia; nephrotoxicity; severe nausea and vomiting (antiemetic therapy is recommended); uric acid nephropathy gout
—Less frequent: Allergic reactions (anaphylaxis, rash, urticaria); alopecia; anorexia; bronchospastic pulmonary disease; CNS toxicity, paresthesia; general weakness, and malaise; injection site sequelae
—Rare:
Cardiovascular: cerebrovascular accident, hypotension, MI, tachyarrhythmia
GI: cramps and diarrhea
Electrolyte imbalances: hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia
Neurotoxicity/CNS toxicity: Ototoxicity, seizure disorder, SIADH syndrome, and dysgeusia
Others: dehydration, facial edema, hiccups, optic neuritis, papilledema, sudden visual loss, thrombotic thrombocytopenic purpura
Drug interactions
• Nephrotoxic drugs
—Concomitant use of amphotericin B and other potentially nephrotoxic drugs should probably be avoided during cisplatin administration
—Cisplatin produces cumulative nephrotoxicity potentiated by aminoglycoside antibiotics
—Risk may be lowered by giving aminoglycoside >2 weeks after cisplatin, if clinically feasible