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Hydration: Induction of diuresis using at least 2000 mL of NS minimizes the risk of cisplatin nephrotoxicity. Fluid administration should be adequate to establish a urine flow of at least 100 mL/hour for two hours prior to and two hours after cisplatin administration. Refer to UpToDate topic on "Cisplatin nephrotoxicity". •

Vesicant/irritant properties: Bleomycin, etoposide, and cisplatin are classified as irritants. Cisplatin can cause significant tissue damage; avoid extravasation [2] . Refer to UpToDate topic on "Extravasation injury from chemotherapy and other non-neoplastic vesicants". •

Infection prophylaxis: Primary prophylaxis with granulocyte colony stimulating factors (G-CSF) is not indicated. Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in patients with chemotherapy-induced neutropenia". • Dose adjustment for preexisting baseline liver or renal dysfunction: Bleomycin should not be administer in patients with a baseline creatinine >2.0 mg/dL. A lower initial dose of cisplatin or etoposide may be needed for patients with renal or hepatic dysfunction [2,3] . Refer to UpToDate topics on "Chemotherapy hepatotoxicity and dose modification in patients with liver disease" and "Chemotherapy-related nephrotoxicity and dose modification in patients with renal insufficiency". Monitoring parameters: • CBC with differential and platelet count weekly during treatment. • Basic metabolic panel (creatinine and electrolytes) prior to each treatment cycle. • Liver function tests prior to each treatment cycle. • Pulmonary function tests, as needed. Suggested dose alterations for toxicity: •

Myelotoxicity: Each cycle should begin on schedule regardless of the degree of myelosuppression [1] . If febrile neutropenia or thrombocytopenic bleeding occurs, a dose reduction of 25 percent for etoposide should be used for subsequent cycles. If neutrophil count remains less than or equal to 2500 cells/mm 3 or platelets remain less than or equal to 100,000/mm 3 , G-CSF should be administered. Refer to UpToDate topic on "Use of granulocyte colony stimulating factors in patients with chemotherapy-induced neutropenia". •

Pulmonary toxicity: Bleomycin can be associated with the development of life-threatening pulmonary toxicity. Bleomycin should be discontinued in patients demonstrating clinical or radiographic evidence of pulmonary injury or significant deterioration of pulmonary diffusion capacity [4] . Do not reintroduce bleomycin to patients with any bleomycin-induced lung injury. Refer to UpToDate topic on "Bleomycin-induced lung injury". •

Neurologic toxicity: Neuropathy usually is seen after cumulative doses of cisplatin beyond 400 mg/m 2 , although there is marked interindividual variation. Patients with mild neuropathy can continue to receive full cisplatin doses. However, if the neuropathy interferes with function, the risk of potentially disabling neurotoxicity must be weighed against the benefit of continued treatment. Peripheral neuropathies can occur with prolonged courses (four to seven months) of cisplatin. Cisplatin treatment should be discontinued with the first signs and symptoms of the development of neurotoxicity [2,5] . Refer to UpToDate topic on "Neurologic complications of platinum-based chemotherapy". •

Renal toxicity: Treatment in the setting of renal impairment (ie, creatinine >2.0 mg/dL or GFR <50 mL/min) requires a balanced discussion of the goals of treatment and the risks of cisplatin nephrotoxiciy in the face of impaired renal function. If there is a change in body weight of at least 10 percent, dose should be recalculated. This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of chemotherapy. The clinician is expected to use his or her independent medical judgment in the context of individual circumstances to make adjustments, as necessary. IV: intravenous; CBC: complete blood count; GFR: glomerular filtration rate. * The precise number of cycles depends on the stage of the germ cell tumor. Δ Cumulative lifetime dose of bleomycin should be limited to 400 units because of the increased rates of pulmonary toxicity. Refer to UpToDate topic on "Bleomycin-induced lung injury". ◊ 1 unit = 1 mg. References: Nichols CR, et al. J Clin Oncol 1998; 16:1287. Platinol (cisplatin) injection, powder, lyophilized, for solution. US FDA-approved manufacturer's package insert. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 8, 2011). Toposar (etoposide) injection. US FDA-approved package insert US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 9, 2011). Blenoxane (bleomycin sulfate) injection. US FDA-approved manufacturer's package insert. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on December 8, 2011). Basch E, et al. Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update. J Clin Oncol 2011; 29:4189.