title: Neoadjuvant chemotherapy for osteosarcoma of the extremity: intensification of preoperative treatment does not increase the rate of good histologic response to the primary tumor or improve the final outcome.
abstract: OBJECTIVE
  The aim of this study was to compare the results in terms of histologic response to primary chemotherapy of two sequential studies in osteosarcoma patients preoperatively treated with methotrexate, doxorubicin, cisplatin, and ifosfamide, given at different doses.
  
  
  METHODS
  Between January 1993 and March 1995, 171 patients with osteosarcoma of the extremity were treated according to a protocol of neoadjuvant chemotherapy with preoperative methotrexate, cisplatin, doxorubicin, and ifosfamide. From April 1995 to December 1999, 196 osteosarcoma patients were preoperatively treated with the same drugs at higher doses. Postoperatively, patients received the same treatment in both studies used, but poor responders (tumor necrosis <95%) had more cycles of treatment than good responders.
  
  
  RESULTS
  Comparing the two chemotherapy regimens, there were no significant differences in terms of good histologic response to chemotherapy (69% vs. 62%), 5-year event-free survival (60% vs. 65%), 5-year overall survival (74% vs. 80%), and rate of local recurrence (6% vs. 4%). The 5-year event-free survival was significantly related to the serum level of alkaline phosphatase before treatment (77% for patients with normal values vs. 46% for patients with high values) and the degree of histologic response to preoperative chemotherapy (69% for good responders vs. 54% for poor responders).
  
  
  CONCLUSIONS
  Increasing the doses of preoperative chemotherapy does not improve the rate of good histologic response and survival in osteosarcoma of the extremity. The degree of necrosis induced by preoperative treatment probably reflects an innate sensitivity to chemotherapy, which is not altered by increasing drug doses.
authors: Chemotherapy, Department of Musculoskeletal Oncology, Istituto Ortopedico Rizzolo, Bologna, Italy. gaetano.bacci@ior.it
authors: Gaetano
authors: G
authors: Bacci
authors: Cristiana
authors: C
authors: Forni
authors: Stefano
authors: S
authors: Ferrari
authors: Alessandra
authors: A
authors: Longhi
authors: Franco
authors: F
authors: Bertoni
authors: Mario
authors: M
authors: Mercuri
authors: Davide
authors: D
authors: Donati
authors: Rodolfo
authors: R
authors: Capanna
authors: Gabriella
authors: G
authors: Bernini
authors: Antonio
authors: A
authors: Briccoli
authors: Elisabetta
authors: E
authors: Setola
authors: Michela
authors: M
authors: Versari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005121:Extremities; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010349:Patient Compliance; D016896:Treatment Outcome