High-dose cisplatin and etoposide in advanced malignancies of childhood.

Thirty-two children with poor-prognosis solid tumors were treated with a combination of high-dose cisplatin (CDDP) (200 mg/m2 over 5 days) and VP16. In the 30 children evaluable for antitumor effect, there were 7 complete, 12 partial, and 3 minor tumor responses. Wilms' tumor and rhabdomyosarcoma responded best. There were no therapy-related deaths. Severe neutropenia (PMN less than 500/mmc) developed after 29 out of the 45 evaluable courses and lasted a median of 8 days; during periods of neutropenia 8 episodes of fever occurred, 1 of which was caused by streptococcal sepsis. Platelet levels were depressed to less than 50,000/mmc after 17/45 cycles and this thrombocytopenia lasted a median of 8 days. No neurological toxicity occurred. One case developed acute renal failure. A hearing deficit for high frequencies was documented in 14/22 patients evaluated after the first cycle and in all cases after the subsequent cycles; the deficits correlated with the total dose of CDDP administered. High-dose cisplatin and VP16 is an effective association in children with advanced cancer, but cumulative dosage is limited by ototoxicity.