Sequence dependence of hematologic toxicity using @entity3003 and XXXX for primary therapy of @entity43 : a phase I study of the Gynecologic Oncology Group.

@entity43 @entity1 @entity137 @entity3003 @entity1311 @entity189 @entity1945
PURPOSE: Selection of a feasible sequence and schedule of @entity3003 in combination with @entity1945 for evaluation in @entity43 (EOC). @entity1 AND METHODS: @entity1 with stages III-IV EOC or primary @entity189 without prior chemotherapy were assigned to consecutive cohorts evaluating a "forward" ( @entity3003 day 1, @entity1945 days 1-3), "reverse" ( @entity3003 day 3, @entity1945 days 1-3), or "extended reverse" sequence ( @entity3003 day 5, @entity1945 days 1-5). @entity1 received 4 cycles @entity3003 - @entity1945 followed by 4 cycles @entity3003 - @entity1311 . Feasibility was defined according to the cumulative proportion of @entity1 with dose-limiting events (DLEs) during the first four cycles. RESULTS: Sixty-eight @entity1 were enrolled across 5 cohorts. The forward sequence demonstrated unacceptable hematologic DLEs at the lowest @entity1945 dose (0.75 mg/m2/day x 3 days). The reverse sequence was feasible at 1.25 mg/m2/day x 3 days, with only 1/15 @entity1 experiencing a DLE within 4 cycles, and 14/15 @entity1 were able to receive 4 subsequent cycles of @entity3003 - @entity1311 . The extended reverse sequence was associated with excessive DLEs at 1.00 mg/m2/day x 5 days. Prophylactic hematopoietic growth factors were not required. CONCLUSION: Higher doses of @entity1945 could be safely administered with reduced @entity137 over multiple cycles using the reverse sequence, which was selected for phase III evaluation. The relative efficacy of the forward and reverse sequence is unknown.
