4045 Background: Preoperative CRT with irinotecan and capecitabine is effective and safe in rectal cancer. Cetuximab, an EGFR- targeted agent, is synergistic with chemotherapy and radiotherapy. We conducted this study to determine efficacy and safety of cetuximab, irinotecan, and capecitabine as a combined preoperative CRT in patients with locally advanced resectable rectal cancer. Methods: This is a non-randomized, open-label, multicenter phase II study with cetuximab 400mg/m2 on D-6 (1 week before radiation) followed by cetuximab 250mg/m2 and irinotecan 40mg/m2 once a week (D1, 8, 15, 22, & 29) and capecitabine 1650mg/m2/day for weekdays only during radiation. Radiotherapy was given to a total dose of 50.4 Gy/28 fractions starting on D1. Main eligibility criteria were histologically proven rectal adenocarcinoma; T3–4 lesions; age 18 - 75 years; ECOG PS 0 - 2; no prior chemotherapy or EGFR targeted therapy. Total mesorectal excision was planned to be performed 4–8 weeks after completion of CRT. Results: Between May 2006 and Dec 2006, 40 patients were enrolled; median age 56.5 years (34 - 72); M/F 32/8; PS 0–1/2 38/2; cT3/T4 36/4; cN0/N+ 8/32; median tumor location from anal verge 5.5cm (0 - 8.0); moderately-differentiated adenocarcinoma 29. At present, 21 patients completed preoperative CRT and were evaluable for toxicity. Grade 3/4 toxicities included leucopenia (2, 9.5%), neutropenia (1, 4.8%), anemia (1, 4.8%) and diarrhea (1, 4.8%). Grade 2 hypersensitivity reactions and skin rashes were observed in 2 (9.5%) and 9 patients (42.9%), respectively and no grade >1 hand-foot syndrome was observed. Of 10 patients who underwent surgery (all R0 resection) till now, 9 were treated with sphincter saving procedure. Pathologic T0 and N0 were observed in 3 and 7 patients, respectively. Pathologic complete responses were observed in 2 patients and another 2 patients had only minimal microscopic residual tumor. Conclusions: Preoperative CRT with cetuximab, irinotecan and capecitabine showed promising preliminary pathologic responses with mild toxicity profiles. Study enrollment has now been completed and further results of efficacy and safety will be presented. No significant financial relationships to disclose.
Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study
