Benefit of intensified therapy for patients with local or regional embryonal rhabdomyosarcoma: Results from the Intergroup Rhabdomyosarcoma Study IV

Purpose: To compare failure-free survival (FFS) and survival for patients with local or regional embryonal rhabdomyosarcoma created on the Intergroup Rhabdomyosarcoma Study (IRS)-IV with that of comparable patients treated on IRS-III. Patients and Methods: Patients were retrospectively classified as low- or intermediate-risk. Low-risk patients were defined as those with primary tumors at favorable sites, completely resected or microscopic residual, or orbit/eyelid primaries with gross residual disease and tumors less than 5 cm at unfavorable sites but completely resected. Intermediate-risk patients were all of her patients with local or regional tumors. Results: Three-year FFS improved from 72% on IRS-III to 78% on IRS-IV for patients with intermediate-risk embryonal rhabdomyosarcoma (P = .02). Subset analysis revealed two groups that benefited most from IRS-IV therapy. FFS at 3 years for patients with resectable node-positive or unresectable (group III) embryonal rhabdomyosarcoma. arising at certain favorable sites (head and neck [not orbit/eyelid or parameningeal] and genitourinary [not bladder or prostate]) improved from 72% on IRS-III to 92% on IRS-IV (P = .01). Similarly, 3-year FFS for patients with completely resected tumor or with only microscopic disease remaining (group I or II) at unfavorable sites improved from 71% on IRS-III to 86% on IRS-IV (P = .04). Only patients with unresectable embryonal rhabdomyosarcoma (group III) at unfavorable sites had no improvement in outcome on IRS-IV (3-year FFS for IRS-III and IRS-IV, 72% and 75%, respectively; P = .31). Conclusion: IRS-IV therapy benefited certain subgroups of patients with intermediate-risk embryonal rhabdomyosarcoma. A doubling of the intensity of cyclophosphamide (or ifosfamide equivalent) dosing per cycle between IRS-III and IRS-IV is thought to be a key contributing factor for this improvement. J Clin Oncol 18:2427-2434. (C) 2000 by American Society of Clinical Oncology.