Phase I-II Trial of Cetuximab, Capecitabine, Oxaliplatin, and Radiotherapy as Preoperative Treatment in Rectal Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 70; no. 4; pp. 1081 - 1086
• Main Authors: Rödel, Claus, M.D, Arnold, Dirk, M.D, Hipp, Matthias, M.D, Liersch, Torsten, M.D, Dellas, Kathrin, M.D, Iesalnieks, Igors, M.D, Hermann, Robert Michael, M.D, Lordick, Florian, M.D, Hinke, Axel, M.D, Hohenberger, Werner, M.D, Sauer, Rolf, M.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.03.2008
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Capecitabine; CARCINOMAS; Cetuximab; Chemoradiotherapy; Combined Modality Therapy - methods; COMBINED THERAPY; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; DIARRHEA; Diarrhea - etiology; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds - administration & dosage; Oxaliplatin; PATIENTS; RADIATION DOSES; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy - adverse effects; Rectal cancer; Rectal Neoplasms - drug therapy; Rectal Neoplasms - radiotherapy; Rectal Neoplasms - surgery; RECTUM; SURGERY; Oxaliplatin; Rectal cancer; Cetuximab; Capecitabine; Chemoradiotherapy
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2007.07.2356

Purpose To evaluate the safety and activity of preoperative radiotherapy (RT) with concurrent cetuximab, capecitabine, and oxaliplatin in rectal cancer patients. Patients and Methods A total of 60 patients with rectal cancer (T3-T4 or N+, M1 allowed) entered the trial at five investigator sites; the data from 58 patients were assessable. Cetuximab was given as an initial dose of 400 mg/m2 7 days before the start of RT, and then at 250 mg/m2 once weekly during RT (50.4 Gy in 28 fractions). Capecitabine and oxaliplatin were administered according to an established schedule of oxaliplatin (50 mg/m2 on Days 1, 8, 22, and 29) and capecitabine (Days 1–14 and 22–35) at three dose levels: 1,000, 1,300, and 1,650 mg/m2 /d during the Phase I part of the study. The main endpoint of the Phase II was the pathologic complete response rate. Results Thirteen patients were included in the Phase I part of the study, and the maximal tolerated dose was not reached. Overall, 48 patients were treated at the recommended dose of capecitabine (1,650 mg/m2 ) and 45 patients (94%) underwent surgery. A pathologic complete response was observed in 4 patients (9%), and moderate ( n = 12), minimal ( n = 10), and no tumor regression ( n = 2) was noted in 24 (53%) of 45 patients. The mean radiation dose intensity, cetuximab, capecitabine, oxaliplatin was 98%, 95%, 94%, and 94%, respectively. The incidence of Grade 3-4 diarrhea was restricted to 19%. Postoperative complications of any grade occurred in 33% of patients. Conclusions The results of our study have shown that cetuximab can be combined safely with capecitabine and oxaliplatin plus RT. The low pathologic complete response rate achieved should stimulate additional preclinical investigations to establish the best sequence of triple combinations.