title: A phase II study of cisplatin, ifosfamide and epirubicin combination chemotherapy in adults with nonmetastatic and extremity osteosarcomas.
abstract: BACKGROUND
  Osteosarcoma is a rare malignancy, and patients with this disease benefit from adjuvant chemotherapy. While cisplatin, anthracyclines and ifosfamide are the most commonly used agents in the treatment of osteosarcoma, a search for the best combination with higher efficacy and minimal toxicity continues. We planned to evaluate the efficacy of epirubicin combined with cisplatin and ifosfamide in patients with localized primary osteosarcoma.
  
  
  METHODS
  Patients with nonmetastatic extremity osteosarcoma who were older than 15 years were included in the study. The preoperative chemotherapy regimen consisted of epirubicin 90 mg/m(2), cisplatin 100 mg/m(2) on day 1 and ifosfamide 2.0 g/m(2)/day with an equivalent dose of mesna on days 2-4, repeated every 21 days. Six cycles of this combination regimen were administered (3 cycles prior to surgery and 3 cycles postoperatively).
  
  
  RESULTS
  Forty-five patients with localized osteosarcoma entered this phase II trial. Median follow-up was 64 months. Thirty-two patients (84%) received the assigned 6 cycles of chemotherapy. Complete and good histological response to neoadjuvant chemotherapy was 26 and 37%, respectively. The 5-year disease-free and overall survival rates were 41.9% (95% CI 33.6-50.2) and 48.2% (95% CI 39.6-56.8). The most prominent grade 4 toxicity was neutropenia occurring in 32% of patients. The lungs were the most frequent site of relapse (32%).
  
  
  CONCLUSIONS
  The combination of cisplatin, ifosfamide and epirubicin is an active, reasonably well-tolerated regimen without grade 3 or 4 cardiac toxicity in patients with nonmetastatic extremity osteosarcoma and deserves further investigation in the context of prospective phase III trials.
authors.affiliation: Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey. basaranm@istanbul.edu.tr
authors.forename: Mert
authors.initials: M
authors.lastname: Basaran
authors.forename: E Sevil
authors.initials: ES
authors.lastname: Bavbek
authors.forename: Sezer
authors.initials: S
authors.lastname: Saglam
authors.forename: Levent
authors.initials: L
authors.lastname: Eralp
authors.forename: Burak
authors.initials: B
authors.lastname: Sakar
authors.forename: Ata Can
authors.initials: AC
authors.lastname: Atalar
authors.forename: Bilge
authors.initials: B
authors.lastname: Bilgic
authors.forename: Harzem
authors.initials: H
authors.lastname: Ozger
authors.forename: Haluk
authors.initials: H
authors.lastname: Onat
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D015251:Epirubicin; D002945:Cisplatin; D007069:Ifosfamide