Docetaxel (DTX) and carboplatin (CP) followed by a dose-ranging study of oral capecitabine, weekly DTX, concomitant radiotherapy and surgery for the treatment of patients with stage II-III carcinoma of the esophagus

Abstract

4049 Background: We previously reported promising phase I data using neoadjuvant weekly DTX and 5-fluorouracil (5-FU) with thoracic irradiation followed by surgery in patients with locally advanced esophageal cancer. This trial was modified in an attempt to improve the pathological complete response rate by increasing the 5-FU exposure during thoracic radiation with oral capecitabine (C). Here we report preliminary results from our dose escalation, trimodality trial. Methods: 18 patients with esophageal cancer (16 = adenocarcinoma, 2 = squamous) were consented and enrolled on this study. Patients (Pts) were staged with a CT scan and endoscopic ultrasound (EUS). Neoadjuvant therapy included DTX, 80 mg/M2, and CP, AUC 6, intravenously every three weeks for 2 cycles. Subsequently, concomitant chemoradiotherapy (CXRT) was initiated with DTX, 15 mg/M2, weekly for five doses and C (7 = 500 mg, 3 = 1000 mg, 8 = 1500 mg) orally prior to each fraction of irradiation (50.4 Gy in 28 fractions). Pts were then restaged with CT and EUS. Transhiatal esophagectomy was performed at 4–8 weeks post CXRT. Results: Patient characteristics: EUS stage, 1 = T3N0, 2 = T2N1, 15 = T3N1. Dose limiting toxicity (DLT), grade 3 dysphagia, occurred in 2 pts (1 = 300 mg, 1 = 1000 mg). No other grade 3 and no grade 4 toxicities were encountered. Only 3 pts required a feeding tube; 11 pts had weight gain over the course of therapy. Antitumor response following chemotherapy and CXRT was 78% (95% confidence interval: 52%–94%) by EUS. To date, 16 of 18 patients have had R0 resection. 2 pts had pathologic CR. Conclusions: Response rates are encouraging using this tri-modality approach. Pts have tolerated combined modality therapy well with minimal side effects, thereby allowing for weight gain without the need for a feeding tube in the majority of enrollees. Capecitabine appears to be a safe agent in this combination up to a dose of 1500 mg. Patient accrual continues at 2000 mg dose level. Funded in part by CA23108, Aventis, and Roche. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis Aventis Abbott; Amgen; Aventis; Bristol-Myers Squibb; Genentech; GlaxoSmithKline; Ortho Biotech; Ligand; Merck; Pfizer; OSI; Roche