Received Dose and Dose-Intensity of Chemotherapy and Outcome in Nonmetastatic Extremity Osteosarcoma

Abstract

PURPOSE: To examine the relationship between received dose, received dose-intensity (RDI), and survival in patients with osteosarcoma. PATIENTS AND METHODS: Between 1983 and 1993, the European Osteosarcoma Intergroup (EOI) conducted two randomized trials involving patients with high-grade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These trials shared a common treatment arm of doxorubicin (DOX) 75 mg/m² and cisplatin (CDDP) 100 mg/m² planned for six cycles at 3-week intervals. Definitive surgery was scheduled at week 9, after three cycles. Survival time was calculated from 122 days, the scheduled end of chemotherapy. RESULTS: A total of 287 patients randomized to DOX/CDDP received at least one cycle of chemotherapy, and 232 (81%) received all six cycles. On average, 79% of the intended dose of DOX and 80% of the intended dose of CDDP was given. Mean time to completion of chemotherapy was 1.27 times that specified by the protocol. Mean RDI was 0.64 for DOX (SD = 0.19) and 0.65 for CDDP (SD = 0.18). Progression-free survival was lower for those who received one to five cycles compared with those who completed all six cycles (hazards ratio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progression-free survival were lowest for patients with RDI less than 0.6, although these differences were not statistically significant at the 5% level. There was no clear evidence of preoperative dose or dose-intensity influencing histologic response. CONCLUSION: This analysis did not establish a clear survival benefit for increasing received dose or dose-intensity in the context of this two-drug regimen. The hypothesis that increasing dose-intensity may improve survival in osteosarcoma requires prospective evaluation.