title: Multiinstitutional phase II study of neoadjuvant chemotherapy for osteosarcoma (NECO study) in Japan: NECO-93J and NECO-95J.
abstract: BACKGROUND
  Osteosarcoma is the most frequent primary malignant bone tumor. In Europe and the United States, its prognosis has been greatly improved by the use of multimodal treatment, including preoperative and postoperative chemotherapy as well as surgery. In Japan, however, only a few clinical studies on osteosarcoma have been carried out.
  
  
  METHODS
  To evaluate the efficacy of neoadjuvant chemotherapy on nonmetastatic, operable osteosarcoma arising in the extremities, a prospective multi-institutional phase II trial, the Neoadjuvant Chemotherapy for Osteosarcoma (NECO) study, was conducted. Preoperative chemotherapy included high-dose methotrexate (HD-MTX), cisplatin (CDDP), and adriamycin (ADR). If the induction therapy was assessed as not effective, high-dose ifosfamide (IFO) was added to the chemotherapy regimen. A total of 124 patients were enrolled in this trial, and ultimately 113 patients were eligible.
  
  
  RESULTS
  The 5-year overall survival (OAS) and event-free survival (EFS) rates in the NECO study were 77.9% and 65.5%, respectively. A good histological response to the induction chemotherapy resulted in favorable OAS (78.7%). The patients assessed as poor histological responders with progressive disease after the induction chemotherapy exhibited comparable outcomes (OAS 89.5%, EFS 68.2%). There were no significant differences between the OAS and EFS rates of the patients in terms of response to preoperative chemotherapy.
  
  
  CONCLUSIONS
  We analyzed the results of the intensive neoadjuvant chemotherapy and the effects of adding IFO on patients with osteosarcoma in Japan. The results suggest efficacy of the high-dose IFO addition to the standard three-drug chemotherapy regimen. However, a randomized clinical study is needed to establish the true impact of IFO on patients with osteosarcoma.
authors: Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan.
authors: Yukihide
authors: Y
authors: Iwamoto
authors: Kazuhiro
authors: K
authors: Tanaka
authors: Kazuo
authors: K
authors: Isu
authors: Akira
authors: A
authors: Kawai
authors: Shin-ichiro
authors: S
authors: Tatezaki
authors: Takeshi
authors: T
authors: Ishii
authors: Kazuyoshi
authors: K
authors: Kushida
authors: Yasuo
authors: Y
authors: Beppu
authors: Masamichi
authors: M
authors: Usui
authors: Akio
authors: A
authors: Tateishi
authors: Kiyoo
authors: K
authors: Furuse
authors: Takeshi
authors: T
authors: Minamizaki
authors: Noriyoshi
authors: N
authors: Kawaguchi
authors: Shinya
authors: S
authors: Yamawaki
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002648:Child; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D020360:Neoadjuvant Therapy / Q000379:methods*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011300:Preoperative Care / Q000379:methods; D011446:Prospective Studies; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult