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

Lookup NU author(s): Emeritus Professor Alan Craft


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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/m(2) and cisplatin (CDDP) 100 mg/m(2) 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 far 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. J Clin Oncol 18:4028-4037. (C) 2000 by American Society of Clinical Oncology.

Publication metadata

Author(s): Lewis, I. J., Weeden, S., Machin, D., Stark, D., Craft, A. W.

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Oncology

Year: 2000

Volume: 18

Issue: 24

Pages: 4028-4037

ISSN (print): 0732-183X

ISSN (electronic): 1527-7755


PubMed id: 11118463

Notes: European Osteosarcoma Intergroup