Induction primary CT with Folfox-4 and cetuximab followed by RT and cetuximab in locally advanced esophageal cancer (LAEC): Analysis of preliminary data from B152 Trial

Abstract

15524 Background: Primary CRT improves the survival of pts with EC when compared with surgery alone.However, the survival benefit conferred by CRT is modest and further improvements in the management of LAEC are required. In EC, increased EGFR expression correlates with a worse prognosis in terms of shorter DFS and OS suggesting the possibility of treatment with anti- EGFR mAb Cetuximab (C). Methods: Based on this background, we initiated a phase II trial to investigate the feasibility of C with FOLFOX- 4 regimen as induction CT followed by C and RT in pts with LAEC. Pts underwent staging with EUS plus biopsies, PET and CT scans. Eligibility: untreated EC; EUS stage II-III; ECOG PS 0–2; adequate organs function; informed consent. All pts received induction treatment with C at a starting dose of 400 mg/m2 and further weekly infusion at a maintenance dose of 250 mg/m2 and 4 cycles of FOLFOX-4 every two weeks. Post-induction EUS and CT scans were performed, while a PET scan was repeated early before second cycle of CT: pts without PD were given daily RT (180cGy fractions to 5040cGy) with concurrent weekly C. Post RT, EUS plus biopsies, CT scan and PET were performed. At wk 18, pts without PD had esophagectomy. The primary end-point was the pathologic complete responses (pCR) rate. According on a two step Simon design, 31 pts have to be enrolled at the first step of the study. In case of 4 or more pCR, the study will be continued and 24 additional pts will be treated. Results: Up to December 2007, 27 pts have been enrolled: 21 men, 6 women, squamous cell carcinoma 18, adenocarcinoma 9, stage II 3 pts, stage III 24 pts. After induction treatment, the following grade 3–4 toxicities were recorded: neutropenia 7%, thrombocytopenia 4%, skin 4%. Between the 16 pts who completed RT and C, the main grade 3–4 toxicities were: esophagitis 6%, skin 12 %. After CRT 3 pts had PD; of the remaining pts, 10 underwent esophagectomy and 3 pts await surgery. All 10 pts had R0 resections:9 pts were downstaged and 1 pt had no change; a pCR was recorded in 4 pts (40%). Conclusions: The integration of CRT with C is well tolerated; the preliminary activity, indicate that this regimen is efficacy suggesting the continuation of the study until the final sample of 55 pts. No significant financial relationships to disclose.