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- Title
Phase 1 adaptive dose-finding study of neoadjuvant gemcitabine combined with radiation therapy for patients with high-risk extremity and trunk soft tissue sarcoma.
- Authors
Tseng, William W.; Zhou, Shouhao; To, Christina A.; Thall, Peter F.; Lazar, Alexander J.; Pollock, Raphael E.; Lin, Patrick P.; Cormier, Janice N.; Lewis, Valerae O.; Feig, Barry W.; Hunt, Kelly K.; Ballo, Matthew T.; Patel, Shreyaskumar; Pisters, Peter W. T.
- Abstract
<bold>Background: </bold>This study was performed to determine the maximum tolerated dose (MTD) of gemcitabine given concurrently with preoperative, fixed-dose external-beam radiation therapy (EBRT) for patients with resectable, high-risk extremity and trunk soft tissue sarcoma (STS).<bold>Methods: </bold>Gemcitabine was administered on days 1, 8, 22, 29, 43, and 50 with EBRT (50 Gy in 25 fractions over 5 weeks). The gemcitabine MTD was determined with a toxicity severity weight method (TSWM) incorporating 6 toxicity types. The TSWM is a Bayesian procedure that choses each cohort's dose to have a posterior mean total toxicity burden closest to a predetermined clinician-defined target. Clinicopathologic and outcome data were also collected.<bold>Results: </bold>Thirty-six patients completed the study. According to the TSWM, the gemcitabine MTD was 700 mg/m(2). At this dose level, 4 patients (24%) experienced grade 4 toxicity; no toxicity-related deaths occurred. All tumors were resected with microscopically negative margins. Pathologic responses of >90% tumor necrosis were achieved in 17 patients (47%); 14 (39%) had complete responses. With a median follow-up of 6.2 years, the 5-year locoregional recurrence-free survival, distant metastasis-free survival, and overall survival rates were 85%, 80%, and 86%, respectively.<bold>Conclusions: </bold>The TSWM combines data from qualitatively different toxicities and can be used to determine the MTD for a drug given as part of a multimodality treatment. Neoadjuvant gemcitabine plus radiation therapy is feasible and safe in patients with high-risk extremity and trunk STS. Major pathologic responses can be achieved, and after complete resection, long-term clinical outcomes are encouraging.
- Publication
Cancer (0008543X), 2015, Vol 121, Issue 20, p3659
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.29544