Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma

Purpose: To examine the relationship between received dose, received dose-i ntensity (RDI), and survival in patients with osteosarcoma. Patients and Methods: Between 1983 and 1993,the European Osteosarcoma Inter group (EOI) conducted two randomized trials involving patients with high-gr ade, nonmetastatic, biopsy-proven osteosarcoma of the extremity. These tria ls shared a common treatment arm of doxorubicin (DOX) 75 mg/m(2) and cispla tin (CDDP) 100 mg/m(2) planned for six cycles at 3-week intervals. Definiti ve surgery was scheduled at week 9, after three cycles. Survival time was c alculated from 122 days, the scheduled end of chemotherapy. Results: A total of 287 patients randomized to DOX/CDDP received at least o ne 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 specifie d 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 r atio, 1.69; 95% confidence interval, 1.03 to 2.78). Survival and progressio n-free survival were lowest for patients with RDI less than 0.6, although t hese differences were not statistically significant at the 5% level, There was no clear evidence of preoperative dose or dose-intensity influencing hi stologic response. Conclusion: This analysis did not establish a clear survival benefit far in creasing received dose or dose-intensity in the context of this two-drug re gimen. The hypothesis that increasing dose-intensity may improve survival i n osteosarcoma requires prospective evaluation. J Clin Oncol 18:4028-4037. (C) 2000 by American Society of Clinical Oncology.