A dose-intensive, cyclophosphamide-based regimen for the treatment of recurrent/progressive or advanced solid tumors of childhood: a report from the Australia and New Zealand Children's Cancer Study Group.

Abstract

Children with solid tumors that progress or recur after conventional multimodality therapies have a very poor prognosis. In a pilot study, vincristine, etoposide, and dose-escalated cyclophosphamide (VETOPEC) was shown to be a promising salvage regimen. Continued accrual of patients and increased duration of follow-up has resulted in substantial experience with VETOPEC. Between May 1991 and March 1994, 56 pediatric patients from 6 centers were enrolled in this study; 44 had recurrent or progressive tumors (Group A) and 12 had newly diagnosed, advanced tumors with a very poor prognosis (Group B). The VETOPEC regimen was comprised of vincristine, 0.05 mg/kg, on Days 1 and 14; etoposide, 2.5 mg/kg, on Days 1, 2, and 3; and fractionated, dose-escalated cyclophosphamide on Days 1, 2, and 3. The initial cyclophosphamide dose was 90 mg/kg (2.7 g/m2)/cycle with an escalation of 15 mg/kg/cycle in each subsequent cycle, to a maximum (over 6 cycles) of 165 mg/kg (5.0 g/m2)/cycle. Tumor response was evaluated every two to three cycles and included central review of imaging. The combined and partial response rates for Groups A and B were 66% (25 of 38 patients) and 91% (10 of 11 patients), respectively. In Group A, best evaluable responses and event free (EF) survivors were observed with: brain tumors (7 of 9 patients; 2 EF at 39 and 45 months [mos], respectively), Wilms' tumor (6 of 7 patients; 3 EF at 37-49 mos), and lymphoma (4 of 4 patients; 2 EF at 52 and 59 mos, respectively); in Group B best evaluable responses and EF were observed with: neuroblastoma (5 of 6 patients; 1 disease free at 57 mos) and rhabdomyosarcoma (4 of 4 patients; no survivors). Hematologic toxicity was limiting despite support with myeloid growth factors in 33 patients. Four deaths in Group A and one in Group B were directly associated with this toxicity. Specifically, no cases of drug-related myocardial toxicity or pneumonitis were observed. This chemotherapy regimen with its intense scheduling produced a high response rate and appreciable survival in patients with a variety of recurrent, progressive, or advanced solid tumors of childhood.