Selective dose escalation of chemoradiotherapy for esophageal cancer: role of treatment intensification

Abstract

This ongoing phase II study is designed to assess the outcomes (survival and failure patterns) of therapy for localized esophageal cancer with conventional dose radiation (50.4 Gy) with concurrent continuous infusion 5-fluorouracil (5-FU) and weekly carboplatin/paclitaxel. Patients with less than complete response or partial response received dose escalation of radiation to 59.4 Gy with the same chemotherapy. This report details the results of the first 18 patients treated. From July 2000 to June 2003, we prospectively enrolled 18 patients with T1-4, N0-1, M0-1a esophageal carcinoma to receive paclitaxel 45 mg/m 2 intravenously over 1 hour and carboplatin AUC 2 intravenously over 30 minutes on days 1, 8, 15, 22, 29, and 36. 5-Fluorouracil 225 mg/m2 was delivered as a continuous infusion on days 1 through 38. Radiation therapy was given 1.8 Gy x 5 days/week x 5.5 weeks (50.4 Gy in 28 fractions). After 6 to 8 weeks, patients underwent repeat staging with computed tomography scan, endoscopic ultrasound, and biopsy. Patients with a positive biopsy, or less than partial response by computed tomography and endoscopic ultrasound, received a boost of 9 Gy with the same concurrent chemotherapy. Patients were followed every 4 months with computed tomography/endoscopic ultrasound the first year and every 6 months thereafter. Median follow-up was 19 months. Eleven of 18 patients (61.1%) attained a complete response/partial response; six of 18 (33.3%) received a boost. Overall survival was 30% at 3 years, with a median of 25 months. Patients with less than 10% pretreatment weight loss had an overall survival of 36% with a median of 26 months. In patients with more than 10% pretreatment weight loss, median survival was 14 months with 0% surviving at 2 years. Local/regional control was 67% (no-boost patients [78%]; boost patients [40%]). Progression-free survival was 31% at 3 years, with a median of 14 months. Distant metastasis-free survival was 40% at 3 years, with a median of 27 months. Seventy-nine percent of patients required at least one dose reduction in chemotherapy because of toxicities. Radiation delays ranged from 0 to 62 days, with a median of 7 days. Grade 2/3 acute esophagitis was experienced by 89% and 39% of patients, respectively; 28% of patients developed esophageal strictures requiring dilatations. The combination of continuous-infusion 5-FU and weekly carboplatin/paclitaxel with selective radiation dose escalation yields promising results without surgery and adjuvant chemotherapy. The toxicities of therapy, while manageable, were significant.