Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy

One-hundred and forty-four patients with osteosarcoma of the extremity trea ted with neoadjuvant chemotherapy at the authors' institution between 1986 and 1989 were retrospectively analyzed to evaluate the relationship between the dose-intensity of chemotherapy actually received (RDI) and the prognos is. Preoperative chemotherapy consisted of high-dose methotrexate i.v., cis platin i.a., and doxorubicin i.v. After surgery 'good responder' patients ( 90% or more tumor necrosis) had a 31-weeks of chemotherapy with the same dr ugs, while 'poor responder' patients (less than 90% tumor necrosis) receive d a 40 weeks treatment with ifosfamide and etoposide added to the three dru gs used preoperatively. Due to delays and dose-reductions, only 17 patients (12%) received the treatment exactly as scheduled by the protocol, 66 (46% ) received a dose-intensity between 90 and 99%, and 61 (42%) a dose-intensi ty between 63 and 89%. At a follow-up ranging between 10 and 13 years, 97 p atients (67%) remained continuously free of disease, 45 relapsed, and two d ied of doxorubicin-induced cardiopathy. The continuos disease-free survival (CDFS) was not related to patients' gender and age, tumor histology, site and size, serum value of alkaline phosphatase, type of surgery and histolog ic response to chemotherapy. According to the RDI, CDFS resulted significan tly higher for those 81 patients who received 90% or more of the scheduled dose-intensity than for those 61 who had less than 90% of the scheduled dos e-intensity (76.5% v.s. 57.3%; p <0.02). These results seem to suggest that in neoadjuvant treatment of osteosarcoma the dose-intensity of chemotherap y is crucial for outcome, therefore every effort should be made to avoid re ductions of doses and/or delays in performing the cycles of chemotherapy.