Increased Pulmonary Toxicity with Bleomycin and Cisplatin Chemotherapy Combinations

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Abstract
Combination chemotherapy that included bleomycin and cisplatin was administered to 45 evaluable patients (30 with cervic carcinoma and 15 with germ cell tumors). Bleomycin was given, following cisplatin infusion, either by intravenous continuous infusion over 72 h (germ cell tumor patients) or intramuscularly every 12 h for 4 days (cervix carcinoma patients). Total bleomycin doses ranged from 156 to 360 U. Nine patients with normal renal function and no previous pulmonary disease prior to chemotherapy developed serious pulmonary toxicity. Six patients died from irreversible respiratory failure. Postmortem lung studies were performed in all six patients and revealed findings compatible with bleomycin-induced lung toxicity. Renal tubular damage was found in four kidneys available for examination. Five (71.5%) of the seven patients whose serum creatinine increased after chemotherapy was initiated developed lung injury, whereas 10.5% of those without change in the serum creatinine level presented this complication (p = 0.001). Renal damage, following cisplatin administration, with subsequent accumulation of bleomycin was the likely cause of the high lung toxicity. Extreme caution is recommended in the administration of combined bleomycin-cisplatin chemotherapy. Whenever possible, bleomycin should precede cisplatin infusion to minimize the risk of lung toxicity.