Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer

• Verfasst von: Hofheinz, Ralf-Dieter [VerfasserIn]
• Verfasst von: Horisberger, Karoline [VerfasserIn]
• Verfasst von: Woernle, Christoph [VerfasserIn]
• Verfasst von: Wenz, Frederik [VerfasserIn]
• Verfasst von: Kraus-Tiefenbacher, Uta [VerfasserIn]
• Verfasst von: Kähler, Georg [VerfasserIn]
• Verfasst von: Dinter, Dietmar [VerfasserIn]
• Verfasst von: Grobholz, Rainer [VerfasserIn]
• Verfasst von: Heeger, Steffen [VerfasserIn]
• Verfasst von: Post, Stefan [VerfasserIn]
• Verfasst von: Hochhaus, Andreas [VerfasserIn]
• Verfasst von: Willeke, Frank [VerfasserIn]
• Titel: Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan, and radiotherapy as neoadjuvant therapy for rectal cancer
• Verf.angabe: Ralf-Dieter Hofheinz, Karoline Horisberger, Christoph Woernle, Frederik Wenz, Uta Kraus-Tiefenbacher, Georg Kähler, Dietmar Dinter, Rainer Grobholz, Steffen Heeger, Stefan Post, Andreas Hochhaus, and Frank Willeke
• E-Jahr: 2006
• Jahr: 18 September 2006
• Umfang: 7 S.
• Fussnoten: Gesehen am 25.02.2022
• Titel Quelle: Enthalten in: International journal of radiation oncology, biology, physics
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1975
• Jahr Quelle: 2006
• Band/Heft Quelle: 66(2006), 5, Seite 1384-1390
• ISSN Quelle: 1879-355X
• DOI: doi:10.1016/j.ijrobp.2006.07.005
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: 5-fluorouracil
• Sach-SW: adjuvant therapy
• Sach-SW: capecitabine
• Sach-SW: carcinomas
• Sach-SW: cetuximab
• Sach-SW: chemoradiation
• Sach-SW: fluorouracil
• Sach-SW: irinotecan
• Sach-SW: leucovorin
• Sach-SW: local-control
• Sach-SW: locally advanced rectal cancer
• Sach-SW: plus irinotecan
• Sach-SW: preoperative chemoradiotherapy
• Sach-SW: radiation-therapy
• Sach-SW: radiotherapy
• K10plus-PPN: 1793951683

Abstract

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(2) on Day 1 and 250 mg/m(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(2) on Days 1, 8, 15, 22, and 29 and capecitabine 800 mg/m(2) on Days 1-38; dose level II, irinotecan 40 mg/m(2) and capecitabine 1000 mg/m(2); and dose level III, irinotecan 50 mg/m(2) and capecitabine 1000 mg/m(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. (c) 2006 Elsevier Inc.