RHABDOMYOSARCOMA TREATMENT

J Clin Oncol. 2012 Jun 4. [Epub ahead of print]

Randomized Comparison of Intensified Six-Drug Versus Standard Three-Drug Chemotherapy for High-Risk Nonmetastatic Rhabdomyosarcoma and Other Chemotherapy-Sensitive Childhood Soft Tissue Sarcomas: Long-Term Results From the International Society of Pediatric Oncology MMT95 Study.

Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D,Stevens MC.

Source

Odile Oberlin, Annie Rey, and Nathalie Bouvet, Institut Gustave-Roussy, Villejuif; Hélène Martelli, Hôpital de Bicêtre, Le Kremlin-Bicetre; Christophe Bergeron, Centre Léon Bérard, Lyon, France; José Sanchez de Toledo, Hospital Universitari Vall d'Hebron, Barcelona, Spain; Meriel E.M. Jenney, Children's Hospital for Wales, Cardiff; Caroline Ellershaw, Children's Cancer and Leukaemia Group, University of Leicester, Leicester; Anna Kelsey, Royal Manchester Children's Hospital, Manchester; David Spooner, Queen Elizabeth Medical Center, Birmingham; Michael C.G. Stevens, Bristol Royal Hospital for Children and University of Bristol, Bristol, United Kingdom; Marcelo Scopinaro, Hospital de Pediatría J.P. Garrahan, Buenos Aires, Argentina; and Johannes H.M. Merks, Emma Children's Hospital, Academic Medical Center, Amsterdam, the Netherlands.

Abstract

PURPOSEMMT95 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 METHODSFrom 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: 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. CONCLUSIONIntensification 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.