Randomized comparison of every-two-week v. every-three-week chemotherapy in Ewing sarcoma family tumors (ESFT)

Abstract

10504 Background: Chemotherapy with alternating cycles of vincristine-doxorubicin-cyclophosphamide and ifosfamide-etoposide, and primary tumor treatment with surgery and/or radiation therapy, is the usual approach to localized ESFT in North America. We conducted a trial asking whether chemotherapy intensification through interval compression could improve outcome. Methods: This was a prospective randomized-controlled trial for patients less than 50 y old with extra-dural ESFT, without distant metastases or prior chemotherapy or radiation therapy; and with adequate renal, cardiac, and hepatic function. Patients were treated with vincristine (2 mg/sq.m, max. 2 mg), doxorubicin (75 mg/sq.m) and cyclophosphamide (1.2 g/sq.m) alternating with ifosfamide (9 g/sq.m) and etoposide (100 mg/sq.m/), for 14 cycles, with filgrastim (5 mg/kg/day, maximum 300 mg) between cycles. Patients assigned to Regimen A were scheduled to begin chemotherapy cycles every 21 days, and patients assigned to Regimen B were scheduled to begin cycles every 14 days, or when ANC ≥ 750 and platelets ≥ 75. Primary tumor treatment (surgery, radiation, or both) was scheduled to begin week 13 (after 4 cycles in Regimen A and 6 cycles in Regimen B). The primary endpoint was event-free survival using a two-sided log-rank test with size 0.05 and power 0.8 to detect a 13% change in EFS from 60%, with 264 patients in each arm. Results: 587 patients were enrolled and randomized, and 568 were eligible, 284 in each regimen. For all courses, the median cycle interval for Regimen A was 21 days, mean 23.3 days; in Regimen B, the median interval was 15 days, mean 18.5 days. Event-free survival at a median of 3 years was 65% in Regimen A and 76% in Regimen B, p=0.028. The occurence of specific toxicities and the number of hospital days were similar for the two regimens. Conclusions: Every-2-week chemotherapy is more effective than every-three-week chemotherapy for localized ESFT, with no increase in toxicity. No significant financial relationships to disclose.