• Karoline Horisberger, Anne Treschl, Sabine Mai, Manuel Barreto-Miranda, Peter Kienle, Philipp Ströbel, Philipp Erben, Christoph Woernle, Dietmar Dinter, Georg Kähler, Andreas Hochhaus, Stefan Post, Frank Willeke, Frederik Wenz, Ralf-Dieter Hofheinz, and MARGIT (Mannheimer Arbeitsgruppe für Gastrointestinale Tumoren).
• Chirurgische Klinik und Poliklinik, Medizinische Fakultät Mannheim der Universität Heidelberg, Germany.
• Int. J. Radiat. Oncol. Biol. Phys. 2009 Aug 1; 74 (5): 1487-93.

PurposeTo evaluate the safety and efficacy of preoperative radiotherapy (RT) in combination with cetuximab, capecitabine, and irinotecan in patients with locally advanced rectal cancer.Methods And MaterialsPatients with rectal cancer (clinical stage T3/4 or N+) were scheduled to receive cetuximab (400 mg/m(2) Day 1, 250 mg/m(2) Days 8, 15, 22, 29) in combination with weekly irinotecan 40 mg/m(2) and capecitabine 500 mg/m(2) twice daily (Days 1-38). RT was given to a dose of 50.4 Gy (45 + 5.4 Gy). Primary endpoint was toxicity, and antitumor activity as assessed by the pathologic complete remission (pCR) rate was a secondary endpoint.ResultsFifty patients were enrolled; 88% showed T3 or T4 and 76% nodal-positive tumors with a median distance from the anal verge of 7.5 cm. The actual dose intensity was as follows (median/mean, %): cetuximab 100/92, irinotecan 100/91, capecitabine 100/89). Main adverse events Grades 2/3/4 were (National Cancer Institute common toxicity criteria version 3.0, %): leukocytopenia 6/2/2, nausea/vomiting 4/2/0, diarrhea 34/30/0, proctitis 26/2/0, elevation of liver transaminases 8/10/0, and acnelike skin rash 46/6/0. All patients underwent surgery, and no postoperative deaths occurred. Eighty-four percent underwent low-anterior resection, and 68% of the specimen exhibited moderate or good tumor regression, but only 4 patients had a pCR.ConclusionPreoperative chemoradiation with cetuximab-CapIri-RT has manageable toxicity, with diarrhea being the most commonly observed adverse event. Nevertheless, the efficacy of this regimen with a pCR rate of only 8% was significantly lower than that observed in a previous Phase I trial.

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