Abstract
Sunitinib (S) is a multi-targeted tyrosine kinase inhibitor. It is synergistic with chemotherapy in preclinical models. We hypothesized that sunitinib in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) would be a tolerable and effective regimen in advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. Since the outcomes of advanced gastric and GEJ adenocarcinoma patients are poor, we decided to study a combination of FOLFIRI + S, to establish tolerability and efficacy. This was a phase I study for patients with advanced chemo-naïve gastric or GEJ adenocarcinoma. Dose escalation used a standard 3 + 3 design. The primary objective was to determine the tolerability and safety of FOLFIRI + S. Secondary objectives were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). A total of 23 patients participated in the study (male 78%, female 22%). The median age was 61 (range: 38-77) years. Median follow-up time was 67.5 (95% CI 58.9-76) months. The most frequently reported adverse events were anemia (78%; G3/4: 4%), neutropenia (78%; G3/4: 43%), nausea (74%; G3/4:13%), diarrhea (65%; G3/4: 4%), vomiting (61%, G3/4: 9%) lymphopenia (52%; G3/4: 13%), and fatigue (52%; G3/4:17%). Two dose-limiting toxicities were noted each at dose level (DL) 1 and 1A, one at DL 1B, and three at DL 2. Maximum tolerated dose was determined at DL 1B. At the time of data reporting, 21 patients had died. The median OS and PFS were 12.4 (95% CI 8.9, 16.5) months and 6.2 (95% CI 3.4, 13.5) months, respectively. Of all patients, 35% (eight out of 23) had a partial response. FOLFIRI + S has signs of clinical activity in patients with advanced gastric and GEJ adenocarcinoma, and the side-effect profile was similar to previously reported studies. Current treatment paradigms in gastric cancer probably negate further study of this regimen. ClinicalTrials.gov identifier: NCT00524186.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
