Phase I/II trial of preoperative oxaliplatin, docetaxel, capecitabine, and radiation for localized esophageal cancer

Abstract

4595 Background: Preoperative chemoradiotherapy is a primary treatment option for patients (pts) with resectable esophageal cancer. Combination regimens using newer agents may improve pt outcomes. This multicenter community-based trial examined a modern triplet regimen comprised of oxaliplatin (O), docetaxel (D), and capecitabine (C) combined with radiation (RT). Methods: The primary endpoints were objective response rate (ORR) and safety. Eligibility criteria: pts with resectable stage I-III cancer of the mid-/distal-esophagus or gastroesophageal junction, measurable disease, ECOG PS 0–1, and informed consent. Treatment: O 40 mg/m2 IV and D 20 mg/m2 IV weekly x 5; C 1,000 mg/m2 PO twice daily D1–7, 15–21, 29–35; and concurrent RT to 45 Gy. Pts were resected 4–8 weeks later. O/D/RT safety was determined in a phase I portion (n=10) before adding C in a phase II portion. Results: 43 pts were enrolled from 9/04 to 12/06 (trial ongoing, n=60 planned). Data on 38 pts are available for analysis. Baseline characteristics: median age 61 years; male/female, 76%/24%; ECOG PS 0/1, 32%/68%; adenocarcinoma/squamous, 74%/26%; and stage I, II, III, 8%/45%/47%. The ORR was 58% (95% CI 42%-72%), with 4 complete and 18 partial responses. 37% had stable disease, and 1 pt had progressive disease (PD). 26 pts (68%) were resected. Unresected pts: awaiting surgery, 3 pts; poor PS, 4 pts; PD, 1 pt; pt choice, 1 pt; death, 3 pts. Pathologic complete responses were seen in 17 pts (65%). With a median follow-up of 16 months, 1-year progression-free survival (PFS) and overall survival (OS) are 58% and 64%, respectively. Median PFS and OS have not been reached. Grade (G) 3/4 non-hematologic toxicity: anorexia (21%), dehydration, esophagitis (16% each), nausea (13%), and dysphagia, fatigue, vomiting, and pain (11% each). Other G3/4 non- hematologic toxicities were = 5%. No G3/4 hematologic toxicities or treatment-related deaths occurred. Conclusions: O/D/C/RT appears safe and active as a preoperative regimen for resectable esophageal cancer - with a G3/4 esophagitis rate that compares favorably with historical combination regimens. Additional accrual and follow-up are needed to determine if these benefits are sustained. No significant financial relationships to disclose.