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A Phase I Study of UFT/Leucovorin, Carboplatin, and Paclitaxel in Combination With External Beam Radiation Therapy for Advanced Esophageal Carcinoma

Journal Article · · International Journal of Radiation Oncology, Biology and Physics
 [1];  [2]; ;  [1];  [2];  [3];  [4]; ;  [1]
  1. Department of Internal Medicine, Division of Medical Oncology and Transplantation, Duke University Medical Center, Durham, NC (United States)
  2. Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)
  3. Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, WV (United States)
  4. Department of General Surgery, Duke University Medical Center, Durham, NC (United States)

Purpose: Concurrent chemotherapy and radiation therapy (RT) are used to treat patients with esophageal cancer. The optimal combination of chemotherapeutic agents with RT is not well established. We evaluated the safety and preliminary efficacy of a combination of UFT/leucovorin, carboplatin, and paclitaxel with RT in a Phase I study of patients with advanced esophageal cancer. Methods and Materials: Patients with squamous cell carcinoma or adenocarcinoma of the esophagus initially received UFT/leucovorin, carboplatin, and paclitaxel with RT (1.8 Gy daily to 45 Gy). After completion, the disease was restaged and patients were evaluated for surgery. Primary end points included determination of dose-limiting toxicities (DLTs) and a recommended Phase II dose. Secondary objectives included determination of non-DLTs, as well as preliminary radiographic and pathologic response rates. Results: Twelve patients were enrolled (11 men, 1 woman). All were assessable for toxicity and efficacy. One of 6 patients at Dose Level 1 (UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, area under the curve [AUC] 5, Weeks 1 and 4; paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4) had a DLT (febrile neutropenia). Of these 6 patients, 4 underwent esophagectomy and none achieved a pathologic complete response. Six patients were then enrolled at Dose Level 2 (UFT/leucovorin, 300/30 mg in the morning and 200/30 mg in the evening on RT days; carboplatin, AUC 5, Weeks 1 and 4; paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4). Two of 6 patients at Dose Level 2 developed DLTs (febrile neutropenia in both). Esophagectomy was performed in 3 patients, with 2 achieving a pathologic complete response. Conclusions: Maximum tolerated doses in this study were UFT/leucovorin, 200/30 mg twice daily on RT days; carboplatin, AUC 5, Weeks 1 and 4; and paclitaxel, 175 mg/m{sup 2} Weeks 1 and 4 when delivered with external RT. In this small study, this regimen appears active, but toxic.

OSTI ID:
21039826
Journal Information:
International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 70; ISSN IOBPD3; ISSN 0360-3016
Country of Publication:
United States
Language:
English

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