title: SFOP OS94: a randomised trial comparing preoperative high-dose methotrexate plus doxorubicin to high-dose methotrexate plus etoposide and ifosfamide in osteosarcoma patients.
abstract: The SFOP-OS94 randomised multi-centre trial was designed to determine whether preoperative chemotherapy regimen combining high-dose methotrexate courses and etoposide-ifosfamide could improve the proportion of good histologic response (5% viable cells) compared to a regimen based on high-dose methotrexate and doxorubicin, in children/adolescents with localised high-grade limb osteosarcoma. Postoperative chemotherapy was adapted to the histologic response. Overall, 234 patients were randomised between 1994 and 2001. There were 56% good responders in the etoposide-ifosfamide arm versus 39% in the doxorubicin arm (p-value=0.009). With a median follow-up of 77 months, the 5-year event-free survival of the entire population was 62%, slightly greater in the etoposide-ifosfamide arm than in the doxorubicin arm, but the difference was not significant (Hazard Ratio: HR=0.71, 95%CI: 0.5-1.06, p-value=0.09). Five-year overall survival of the entire population was 76%, similar in both arms (HR=0.95, 95%CI: 0.6-1.6, p-value=0.85). Toxicity was manageable with different acute toxicity profiles between treatment arms. No acute toxicity related death was reported. About 43% of the patients in the etoposide-ifosfamide arm were event-free at 3 years without having received any doxorubicin or cisplatin, thus avoiding the risk of long-term cardio- and ototoxicity.
authors.affiliation: Service de Biostatistique et d'Epidémiologie, Institut Gustave-Roussy, 39, rue Camille Desmoulins, 94805 Villejuif Cedex, France. le_deley@igr.fr
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Le Deley
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Guinebretière
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Gentet
authors.forename: Hélène
authors.initials: H
authors.lastname: Pacquement
authors.forename: Fabienne
authors.initials: F
authors.lastname: Pichon
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec-Bérard
authors.forename: Natacha
authors.initials: N
authors.lastname: Entz-Werlé
authors.forename: Claudine
authors.initials: C
authors.lastname: Schmitt
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Daniel
authors.initials: D
authors.lastname: Vanel
authors.forename: Noëlle
authors.initials: N
authors.lastname: Dupoüy
authors.forename: Marie-Dominique
authors.initials: MD
authors.lastname: Tabone
authors.forename: Chantal
authors.initials: C
authors.lastname: Kalifa
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy* / Q000601:surgery; D011300:Preoperative Care / Q000379:methods
chemical_list: D005047:Etoposide; D004317:Doxorubicin; D007069:Ifosfamide; D008727:Methotrexate