High-dose cyclophosphamide, adriamycin, and vincristine (HD-CAV) in children with recurrent solid tumor

A dose-intensive regimen of cyclophosphamide (140 mg/kg over 2 days), doxorubicin (Adriamycin, 75 mg/m2 over 3 days), and vincristine (1 mg/m2 on days 1, 2, and 3 and 1.5 mg/m2 on day 9) was tested in 18 children and adolescents with poor-prognosis recurrent or refractory solid tumors. Nine were affected by neuroblastoma, 3 by Ewing's tumors, 2 by rhabdomyosarcoma, 2 by synovial sarcoma, 1 by hepatocellular carcinoma, and 1 by osteogenic sarcoma. All enrolled patients were heavily pretreated, including 2 patients after bone marrow transplantation. Forty courses were applied (median, 2). The overall response rate was 33% (2 complete remissions and 4 partial remissions). Responses were obtained in children with neuroblastoma, Ewing's tumors, and hepatocellular carcinoma. Myelosuppression [World Health Organization (WHO) grade IV after all courses] and cardiac toxicity (3 WHO grade I, 5 WHO grade III, and 3 WHO grade IV) were the main side effects. Nephrotoxicity and hepatoxicity were not observed. With further therapy consisting of surgery, radiotherapy, and high-dose chemotherapy [cisplatin, carboplatin/etoposide (VP16), or ifosfamide/VP16 with or without autologous stem cell reinfusion after conditioning with melphalan/VP16/carboplatin], 3 complete remissions and 5 very good partial remissions were obtained. Ten of 18 patients are alive after a median follow-up of 16 months.