Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma: A Report From the Children’s Oncology Group

Abstract

Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

Risk‐based treatment for patients with first relapse or progression of rhabdomyosarcoma: A report from the Children's Oncology Group

“…The response rate of 31.5% for VI was modest, particularly in comparison with the 70% response rate seen in an upfront phase 2 window trial of previously untreated patients with metastatic RMS . After the investigation of the VI phase 2 window in the first‐relapse setting for RMS, the combination was investigated with alternating cycles of VAC chemotherapy in newly diagnosed patients with intermediate‐risk RMS by COG (ARST0531), but it failed to improve outcomes . The objective response rate in this trial for TPZ, doxorubicin, and cyclophosphamide ranged from 22% to 54%.…”

Increased local failure for patients with intermediate‐risk rhabdomyosarcoma on ARST0531: A report from the Children's Oncology Group

“…9,12 The objective of the current analysis was to determine local control among patients treated on ARST0531 in comparison with those treated on D9803. 9,12 The objective of the current analysis was to determine local control among patients treated on ARST0531 in comparison with those treated on D9803.…”

Do children and adolescents with completely resected alveolar rhabdomyosarcoma require adjuvant radiation? A report from the Children's Oncology Group

“…Patients enrolled on ARST0531 were randomized to receive VAC therapy or VAC with cycles of vincristine and irinotecan 18 . The dose of cyclophosphamide was reduced from 2.2 g/m 2 /course on D9803 to 1.2 g/m 2 /course on ARST0531.…”