title: Dose-intense ifosfamide/doxorubicin/cisplatin based chemotherapy for osteosarcoma in adults.
abstract: The efficacy of neoadjuvant and adjuvant chemotherapy has been clearly established in the treatment of osteosarcoma; however, the most active regimen remains to be identified. This prospective study evaluated the efficacy and toxicity of a dose-intense ifosfamide, doxorubicin, and cisplatin-based neoadjuvant regimen in adults with osteosarcoma. We prospectively treated 20 patients with osteogenic sarcoma with two cycles of ifosfamide/doxorubicin followed by two cycles of doxorubicin/cisplatin every 2 weeks. Surgical specimens were analyzed for percent tumor necrosis. Patients who demonstrated a "good response" (GR) to chemotherapy received the same combination postoperatively at a lower dose rate. Patients who demonstrated a "poor response" (PR) received four cycles of high-dose methotrexate alternating with two cycles of ifosfamide/etoposide and two cycles of cisplatin/etoposide after the surgery. Neoadjuvant chemotherapy was well tolerated with moderate hematologic toxicity. Twelve of 19 evaluable patients (63%) were treated according to the GR arm and 7 according to the PR arm. At median follow-up of 5.5 years, disease-free survival (DFS) and overall survival (OS) are 68% and 74%, respectively. Patients treated on the GR arm had DFS and OS of 75% and 83%, respectively, whereas patients on the PR arm had DFS and OS of 57%. Intensive neoadjuvant chemotherapy is effective and moderately well tolerated in patients with de novo osteosarcoma. The outcome data suggest that lack of a near complete response to preoperative chemotherapy reflects inherent biologic resistance to chemotherapy and hence a poor prognosis.
authors.affiliation: Division of Hematology and Oncology, University of Florida College of Medicine, Gainesville, Florida, USA.
authors.forename: Shailesh J
authors.initials: SJ
authors.lastname: Patel
authors.forename: James W
authors.initials: JW
authors.lastname: Lynch
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.forename: Robert R
authors.initials: RR
authors.lastname: Carroll
authors.forename: Cynthia
authors.initials: C
authors.lastname: Schumacher
authors.forename: Susanne
authors.initials: S
authors.lastname: Spanier
authors.forename: Mark
authors.initials: M
authors.lastname: Scarborough
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D004317:Doxorubicin; D002945:Cisplatin; D007069:Ifosfamide