Infusional 5-Fluorouracil and ZD1839 (Gefitinib-Iressa) in Combination With Preoperative Radiotherapy in Patients With Locally Advanced Rectal Cancer: A Phase I and II Trial (1839IL/0092)
- Department of Radiation, Catholic University of the Sacred Heart, Rome (Italy)
- Department of Radiation Therapy, Centro Referimento Oncologico, Aviano (Italy)
- Department of Surgery, Catholic University of the Sacred Heart, Rome (Italy)
- Department of Pathology, Catholic University of the Sacred Heart, Rome (Italy)
- Department of Radiology, Catholic University of the Sacred Heart, Rome (Italy)
- Department of Surgery, Centro Referimento Oncologico, Aviano (Italy)
- Department of Radiation Therapy, University of Perugia, Perugia (Italy)
Purpose: To report the final data of a Phase I and II study (1839IL/0092) on the combination of an anti-epidermal growth factor receptor drug (gefitinib), infusional 5-fluorouracil, and preoperative radiotherapy in locally advanced, resectable rectal cancer. Methods and Materials: Patients received 45 Gy in the posterior pelvis plus a boost of 5.4 Gy on the tumor and corresponding mesorectum. Infusional 5-fluorouracil (5-FU) and gefitinib (250 and 500 mg/day) were delivered during all radiotherapy course. An IORT boost of 10 Gy was allowed. The main endpoints of the study were to establish dose-limiting toxicity (DLT) and to evaluate the rate of pathologic response according to the tumor regression grade (TRG) Mandard score. Results: A total of 41 patients were enrolled. The DLT was not reached in the 6 patients enrolled in the dose-escalation part of the study. Of the 33 patients in the Phase II, TRG 1 was recorded in 10 patients (30.3%) and TRG 2 in 7 patients (21.2 %); overall 17 of 33 patients (51.5%) had a favorable endpoint. Overall, Grade 3+ toxicity was recorded in 16 patients (41%); these included Grade 3+ gastrointestinal toxicity in 8 patients (20.5%), Grade 3+ skin toxicity in 6 (15.3%), and Grade 3+ genitourinary toxicity in 4 (10.2%). A dose reduction of gefitinib was necessary in 24 patients (61.5%). Conclusions: Gefitinib can be associated with 5-FU-based preoperative chemoradiation at the dose of 500 mg without any life-threatening toxicity and with a high pCR (30.3%). The relevant rate of Grade 3 gastrointestinal toxicity suggests that 250 mg would be more tolerable dose in a neaoadjuvant approach with radiotherapy and infusional 5-FU.
- OSTI ID:
- 21128191
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 3 Vol. 72; ISSN IOBPD3; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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