Abstract
10013 Background: Patients with RMS have a poor prognosis at first relapse/disease progression. CPT-11 has significant and schedule-dependent preclinical activity in RMS, and prolonged exposure results in increased efficacy. Methods: Patients with biopsy proven RMS, < 21 years of age at original diagnosis and unfavorable prognosis at first relapse/progression were eligible. Entry criteria were: life expectancy ≥ 2 months, performance status ≤ 2, adequate organ function and written informed consent. Patients were randomized to one of two schedules of CPT-11/VCR: Regimen 1A: CPT-11, 20 mg/m2 intravenously (IV) daily × 5d × 2w on weeks 1 and 4, VCR 1.5 mg/m2 IV on day 1 of weeks 1, 2, 4 and 5; Regimen 1B: CPT-11, 50 mg/m2 IV daily × 5d on weeks 1 and 4, VCR identical to IA. Disease response at week 6 was assessed using RECIST. Secondary endpoints included toxicity, progression free survival (PFS) and survival (OS). The study was powered to detect a 25% improvement in response to IA when compared to IB (α=0.1, 1-β=0.9, 1-sided test). Those with responsive/stable disease continued to receive 44 weeks of standard multi-agent chemotherapy (doxorubicin, cyclophosphamide, etoposide, ifosfamide) in combination with their assigned CPT- 11/VCR regimen. Results: 92 patients were randomized (IA-45, IB-47). Response in 86 evaluable patients was: 1A - 4 CR, 6 PR, 11 SD, 19 PD (overall response 25%) 1B - 0 CR, 17 PR, 14 SD, 15 PD (overall response 37%) (p=0.23). The 1-year PFS on IA was 32% (95% CI: 18%, 47%) and for IB was 36% (95% CI: 22%, 50%). The 1-year OS for IA was 47% (95% CI: 30%, 62%) and 1B was 56% (95% CI: 40%, 69%). There were no unexpected toxicities or significant differences in toxicity between the two regimens. Conclusions: There was no difference in the response rates between the two CPT-11/VCR regimens. The shorter, more convenient CPT-11/VCR regimen is now being investigated in frontline Children’s Oncology Group RMS clinical trials. No significant financial relationships to disclose.
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