Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer
- Onkologisches Zentrum, III, Medizinische Klinik, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim (Germany)
- Chirurgische Klinik, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim (Germany)
- Klinik fuer Strahlentherapie und Radioonkologie, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim (Germany)
- Institut fuer Klinische Radiologie, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim (Germany)
- Pathologisches Institut, Fakultaet fuer Klinische Medizin Mannheim der Universitaet Heidelberg, Mannheim (Germany)
- Merck Pharma KGaA, Darmstadt (Germany)
Purpose: To establish the feasibility and efficacy of chemotherapy with capecitabine, weekly irinotecan, cetuximab, and pelvic radiotherapy for patients with locally advanced rectal cancer. Methods and materials: Twenty patients with rectal cancer (clinical Stage uT3-T4 or N+) received a standard dosing regimen of cetuximab (400 mg/m{sup 2} on Day 1 and 250 mg/m{sup 2} on Days 8, 15, 22, and 29) and escalating doses of irinotecan and capecitabine according to phase I methods: dose level I, irinotecan 40 mg/m{sup 2} on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m{sup 2} on Days 1-38; dose level II, irinotecan 40 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}; and dose level III, irinotecan 50 mg/m{sup 2} and capecitabine 1000 mg/m{sup 2}. Radiotherapy was given to a dose of 50.4 Gy (45 Gy plus 5.4 Gy). Resection was scheduled 4-5 weeks after termination of chemoradiotherapy. Results: On dose level I, no dose-limiting toxicities occurred; however, Grade 3 diarrhea affected 1 of 6 patients on dose level II. Of 5 patients treated at dose level III, 2 exhibited dose-limiting toxicity (diarrhea in 2 and nausea/vomiting in 1). Therefore, dose level II was determined as the recommended dose for future studies. A total of 10 patients were treated on dose level II and received a mean relative dose intensity of 100% of cetuximab, 94% of irinotecan, and 95% of capecitabine. All patients underwent surgery. Five patients had a pathologically complete remission and six had microfoci of residual tumor only. Conclusion: Preoperative chemoradiotherapy with cetuximab, capecitabine, and weekly irinotecan is feasible and well tolerated. The preliminary efficacy is very promising. Larger phase II trials are ongoing.
- OSTI ID:
- 20850261
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 66, Issue 5; Other Information: DOI: 10.1016/j.ijrobp.2006.07.005; PII: S0360-3016(06)01162-X; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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