Concurrent paclitaxel/carboplatin/infusional 5-FU/radiation therapy (RT) with or without subsequent esophageal resection in patients with localized esophageal cancer: A Minnie Pearl Cancer Research Network trial

Abstract

4018 Background: Optimal treatment for patients (pts) with localized esophageal cancer is unclear. In various reported trials, results with concurrent chemotherapy/RT have been comparable to results with treatment programs containing surgical resection. We previously demonstrated the efficacy of preoperative concurrent paclitaxel/carboplatin/5FU/RT in a large phase II trial (41% 3-yr PFS). In this trial, we attempt to further define the role of surgical resection by randomizing pts to resection vs completion of full dose RT, following the same preop therapy. Methods: Eligibility: untreated esophageal/GE junction squamous or adenocarcinoma; clinical stage I-III; surgical candidate; ECOG PS 0–2; adequate organ function; informed consent. All pts received paclitaxel 200mg/m2 IV and carboplatin AUC 6.0 IV, days 1 & 22; 5-FU 225mg/m2/day, 24-h continuous infusion, days 1–42; radiation therapy 45 Gy (1.8 Gy single daily fractions). After completion of preop treatment, pts were randomized to either surgical resection (4–6 weeks after preop therapy) or continued RT (total dose 64.8 Gy) plus 1 additional course of paclitaxel/carboplatin. Overall survival and PFS were the major endpoints. Results: Between 10/99 and 10/04, 194 pts were treated: median age 60 years; male/female 81%/19%; adenocarcinoma 72%; distal or GE junction location 84%; clinical stage I vs II/III 9%/91%. Following chemotherapy/RT, 89 pts (46%) agreed to randomization, and 57 pts proceeded with the treatment to which they randomized. When all patients are considered, resected pts (N=91) and full dose RT pts (N=50) had similar median PFS (20 vs 15 mo; p=.92), OS (27 vs 24 mo; p=.74), and 3-yr survival (35% vs 31%). Comparisons were similar in the subset of randomized pts. 4 pts (2%) had treatment-related death during induction; 3 pts (3%) had postop death. Conclusions: Attempts to randomize pts to resection vs full dose RT were largely unsuccessful. However, in large parallel groups of pts, these treatments produced similar PFS and OS, suggesting resection may not be a required component of combined modality treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb