Dose-intense ifosfamide/doxorubicin/cisplatin based chemotherapy for osteosarcoma in adults.

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.
AuthorsShailesh J Patel, James W Lynch Jr, Thomas Johnson, Robert R Carroll, Cynthia Schumacher, Susanne Spanier, Mark Scarborough
JournalAmerican journal of clinical oncology (Am J Clin Oncol) Vol. 25 Issue 5 Pg. 489-95 (Oct 2002) ISSN: 0277-3732 [Print] United States
PMID12393991 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Doxorubicin
  • Cisplatin
  • Ifosfamide
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
  • Bone Neoplasms (drug therapy, pathology, surgery)
  • Cisplatin (administration & dosage)
  • Doxorubicin (administration & dosage)
  • Histiocytoma, Benign Fibrous (drug therapy, pathology, surgery)
  • Humans
  • Ifosfamide (administration & dosage)
  • Middle Aged
  • Neoadjuvant Therapy
  • Osteosarcoma (drug therapy, secondary, surgery)
  • Prospective Studies
  • Survival Analysis

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