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.