title: Nonmetastatic osteosarcoma of the extremity. Neoadjuvant chemotherapy with methotrexate, cisplatin, doxorubicin and ifosfamide. An Italian Sarcoma Group study (ISG/OS-Oss).
abstract: BACKGROUND
  Based on the results of the ISG/OS-1 study, the MAP regimen (methotrexate [MTX], doxorubicin [ADM] and cisplatin [CDP] with the addition of ifosfamide [IFO] in poor-responder patients) was investigated in patients with nonmetastatic osteosarcoma of the extremity (ISG/OS-Oss study).
  
  
  METHODS
  Compared with the ISG/OS-1 study (cumulative doses: ADM 420 mg/m(2), MTX 120 g/m(2), CDP 600 mg/m(2), IFO 30 g/m(2)), the ISG/OS-Oss study reduced the number of MTX cycles from 10 to 5 (cumulative MTX dose: 60 g/m(2)) in order to diminish treatment duration and toxicity.
  
  
  RESULTS
  From January 2007 to June 2011, 171 patients (median age 16 years, 60% males) were registered. The limb salvage rate was 94% and the good pathologic response rate 51% (these figures were 92% and 48%, respectively, in the ISG/OS-1 study). At a median follow-up of 39 months (range, 4-80), the 5-year overall survival rate was 80% (95% CI, 73%-87%) and the event-free survival was 50% (95% CI, 39%-59%). For comparison, the 5-year overall and event-free survival rates in ISG/OS-1 were 73% (95% CI, 65%-81%) and 64% (95% CI, 56%-73%), respectively.
  
  
  CONCLUSIONS
  This study confirms that in nonmetastatic osteosarcoma of the extremity, conservative surgery in more than 90% and a good pathologic response rate of 50% can be expected with primary chemotherapy based on the MAP regimen. The response and resection rates in the ISG/OS-Oss study are in the same range as those of the previous study, whereas the event-free survival is lower than that previously achieved. Since the only difference between the two studies was the cumulative dose of postoperatively given MTX, our data support the importance of the cumulative dose of MTX in the MAP regimen.
authors: Stefano
authors: S
authors: Ferrari
authors: Cristina
authors: C
authors: Meazza
authors: Emanuela
authors: E
authors: Palmerini
authors: Angela
authors: A
authors: Tamburini
authors: Franca
authors: F
authors: Fagioli
authors: Raffaele
authors: R
authors: Cozza
authors: Virginia
authors: V
authors: Ferraresi
authors: Gianni
authors: G
authors: Bisogno
authors: Maurizio
authors: M
authors: Mascarin
authors: Graziella
authors: G
authors: Cefalo
authors: Marco
authors: M
authors: Manfrini
authors: Rodolfo
authors: R
authors: Capanna
authors: Roberto
authors: R
authors: Biagini
authors: Davide
authors: D
authors: Donati
authors: Piero
authors: P
authors: Picci
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007558:Italy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D020360:Neoadjuvant Therapy / Q000379:methods*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology* / Q000601:surgery; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide; D008727:Methotrexate