PURPOSE: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome. EXPERIMENTAL DESIGN: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others). RESULTS: Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years. CONCLUSIONS: A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.
PURPOSE: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome. EXPERIMENTAL DESIGN: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others). RESULTS: Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years. CONCLUSIONS: A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.
Authors: Daniel M Green; Larry E Kun; Katherine K Matthay; Anna T Meadows; William H Meyer; Paul A Meyers; Sheri L Spunt; Leslie L Robison; Melissa M Hudson Journal: Pediatr Blood Cancer Date: 2013-02-15 Impact factor: 3.167
Authors: Douglas S Hawkins; Yueh-Yun Chi; James R Anderson; Jing Tian; Carola A S Arndt; Lisa Bomgaars; Sarah S Donaldson; Andrea Hayes-Jordan; Leo Mascarenhas; Mary Beth McCarville; Jeannine S McCune; Geoff McCowage; Lynn Million; Carol D Morris; David M Parham; David A Rodeberg; Erin R Rudzinski; Margarett Shnorhavorian; Sheri L Spunt; Stephen X Skapek; Lisa A Teot; Suzanne Wolden; Torunn I Yock; William H Meyer Journal: J Clin Oncol Date: 2018-08-09 Impact factor: 44.544
Authors: Abha A Gupta; James R Anderson; Alberto S Pappo; Sheri L Spunt; Roshni Dasgupta; Daniel J Indelicato; Douglas S Hawkins Journal: Cancer Date: 2011-07-14 Impact factor: 6.860
Authors: Carola A S Arndt; Julie A Stoner; Douglas S Hawkins; David A Rodeberg; Andrea A Hayes-Jordan; Charles N Paidas; David M Parham; Lisa A Teot; Moody D Wharam; John C Breneman; Sarah S Donaldson; James R Anderson; William H Meyer Journal: J Clin Oncol Date: 2009-09-21 Impact factor: 44.544
Authors: Navin Pinto; Sandi L Navarro; Christine Rimorin; Michelle Wurscher; Douglas S Hawkins; Jeannine S McCune Journal: Pediatr Blood Cancer Date: 2021-07-10 Impact factor: 3.167