Up-front window trial of topotecan in previously untreated children and adolescents with metastatic rhabdomyosarcoma: An Intergroup Rhabdomyosarcoma Study

Purpose: To investigate the antitumor activity and toxicity of topotecan, u sed alone and in combination with conventional therapy, in patients with me tastatic rhabdomyosarcoma (RMS). Patients and Methods: Forty-eight patients younger than 21 years of age wit h newly diagnosed metastatic RMS received 2.0 to 2.4 mg/m(2) of topotecan i ntravenously daily for 5 days every 21 days before standard therapy. Two co urses were given in the absence of progressive disease or excessive toxicit y and response was assessed. Patients with at least a partial response (PR) to topotecan proceeded to therapy with alternating courses of vincristine 1.5 mg/m(2), dactinomycin 1.5 mg/m(2), and cyclophosphamide 2.2 g/m(2) (VAC ) and vincristine 1.5 mg/m(2), topotecan 0.75 mg/m(2) daily x 5, and cyclop hosphamide 250 mg/m(2) daily x 5. Patients who did not respond to topotecan received continuation therapy with VAC alone. Results: The overall response rate to topotecan was 46% (complete response, 4%; partial response 42%). Unexpectedly, patients with alveolar RMS had a higher rate of response (65%) than those with embryonal RMS (28%; P = .08). The most common grade 3 or 4 toxicities were neutropenia (67%), anemia (33 %), thrombocytopenia (25%), and infection (21%). Two-year failure-free surv ival and survival estimates were 24% and 46%, respectively. Response to win dow therapy did not correlate with survival. Conclusion: The high response rate and acceptable toxicity profile of topot ecan in children with advanced RMS support further evaluation of this agent in phase III trials. The superior responses in alveolar RMS are of interes t. J Clin Oncol 19:213-219. (C) 2001 by American Society of Clinical Oncolo gy.