PURPOSE:MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. PATIENTS AND METHODS: From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms), epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. RESULTS:Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. CONCLUSION: Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity.
RCT Entities:
PURPOSE: MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. PATIENTS AND METHODS: From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m(2) (both arms), epirubicin 450 mg/m(2), etoposide 1,350 mg/m(2) (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. RESULTS: Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. CONCLUSION: Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity.
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: J H M Merks; G L De Salvo; C Bergeron; G Bisogno; A De Paoli; A Ferrari; A Rey; O Oberlin; M C G Stevens; A Kelsey; J Michalski; D S Hawkins; J R Anderson Journal: Ann Oncol Date: 2014-01 Impact factor: 32.976
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Authors: David O Walterhouse; Donald A Barkauskas; David Hall; Andrea Ferrari; Gian Luca De Salvo; Ewa Koscielniak; Michael C G Stevens; Hélène Martelli; Guido Seitz; David A Rodeberg; Margarett Shnorhavorian; Roshni Dasgupta; John C Breneman; James R Anderson; Christophe Bergeron; Gianni Bisogno; William H Meyer; Douglas S Hawkins; Veronique Minard-Colin Journal: J Clin Oncol Date: 2018-10-23 Impact factor: 44.544
Authors: Odile Oberlin; Annie Rey; Kenneth L B Brown; Gianni Bisogno; Ewa Koscielniak; Michael C G Stevens; Douglas S Hawkins; William H Meyer; Trang H La; Modesto Carli; James R Anderson Journal: Pediatr Blood Cancer Date: 2015-08-10 Impact factor: 3.167
Authors: Abby R Rosenberg; James R Anderson; Elizabeth Lyden; David A Rodeberg; Suzanne L Wolden; Simon C Kao; David M Parham; Carola Arndt; Douglas S Hawkins Journal: Eur J Cancer Date: 2013-12-18 Impact factor: 9.162