Intensive chemotherapy for metastatic neuroblastoma: a Southwest Oncology Group study

Thirty-three children with Evans stage IV neuroblastoma were treated with an intensive chemotherapy regimen reported by Helson to be highly effective. The purpose of the study was to determine whether the toxic regimen was manageable by different investigators and to increase the sample of patients. Remission induction therapy consisted of courses repeated every four weeks: Cyclophosphamide (CTX) 80 mg/kg IV, with IV fluids, and furosemide on days 1 and 2; vincristine (VCR) 0.03 mg/kg IV 12 hours after cyclophosphamide; trifluoro-methyl-2-deoxyridine (F3TdR) 45 mg/kg IV push, and papaverine (PAP) 45 mg/kg (12-hour infusion) under cardiac monitoring on days 3 and 4. Initially during maintenance, courses of therapy were reduced to two days. Because this was found to be ineffective therapy, the courses were extended to four days. Some of the patients who achieved response were removed from the protocol and placed on different maintenance therapy. Seventeen of 21 children newly diagnosed and 6/12 children previously treated for metastatic neuroblastoma achieved partial or complete remission. Eight of 16 newly diagnosed patients achieving response are still alive, six without evidence of disease for periods of time ranging from 20 to 41 months. The median of the administered drug dosages was 100% of the recommended dosages. Seventy percent of the 229 courses given were initiated at correct interval. Therapy had to be delayed on the others because of toxicity. The value of the four-drug combination is limited because of side effects related to myelosuppression which resulted in severe complications and frequent hospitalizations.