Effect of dose intensity of methotrexate, doxorubicin, and ifosfamide on the prognosis of patients with osteosarcoma

Background. The prognosis of patients with osteosarcoma has improved due to the introduction of systemic chemotherapy. The current study tried to identify the effect of each anti-tumor drug on the prognosis of patients with osteosarcoma. Methods. The records of 29 patients with osteosarcoma who received systemic chemotherapy were retrospectively analyzed. All tumors were classified as stage IIB (Enneking's surgical stage) and were located around the knee joint or more distal areas. The histologic response to preoperative chemotherapy was determined in 20 patients: 9 patients had grade 1, 4 grade 2, 5 grade 3, and 2 grade 4. The mean follow-up period was 102 months. Results. The 5-year overall survival and relapse-free survival (RFS) in the 29 patients was 47.7% and 41.4%, respectively. The 5-year RFS for the 7 good responders (grade 3 and 4) was 85.7%, and that for the 13 poor responders (grade 1 and 2) was 23.1% (P = 0.008). The mean preoperative dose intensity (DI) of methotrexate (MTX) for good responders was significantly higher than that for poor responders (P = 0.028). In 23 patients who received MTX and doxorubicin (ADR) but not ifosfamide (IFOS), the DI of MTX significantly influenced the RFS (P = 0.0128). In the 13 poor responders, 6 of whom received IFOS, the DI of IFOS and ADR significantly influenced RFS (P = 0.0112, 0.0395). Conclusion. The preoperative DI of MTX was related to the histologic response rate. The DI of MTX was significartly associated with the patients' RFS. In poor responders, the DI of IFOS and ADR influenced the patients' RFS. Received: November 17, 1997 / Accepted: July 9, 1998