A phase I clinical trial of combination therapy with gemcitabine and epitope peptides derived from human vascular endothelial growth factor receptor for patients with advanced pancreatic cancer.

Abstract

e13138 Background: Vascular endothelial growth factor receptors (VEGFR) were reported to be a promising target for antiangiogenic cancer immunotherapy. Therefore, a phase I clinical trial of combination therapy with gemcitabine and epitope peptides derived from VEGFR1 and VEGFR2 was conducted for patients with advanced pancreatic cancer. The aim of this study was to evaluate the safety, immunological response, and tumor response. Methods: Patients with metastatic and unresectable pancreatic cancer were eligible for the trial. Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1, 8, and 15 in a 28-day cycle. Epitope peptides derived from VEGFR1 (VEGFR1-1084) and VEGFR2 (VEGFR2-169) were subcutaneously injected on days 3, 10, 17, and 24 in a dose-escalation manner (doses of 0.5, 1, and 3 mg/body, three patients/one cohort). Results: Nine patients were enrolled in this trial. During the clinical course, no major adverse events of grade 4 or higher were observed. So no dose-limiting toxicity was found in this trial. Two patients who showed grade 2 reaction at the injection site were judged as having partial response of the tumor. The analysis of immunological parameters including measurement of the specific cytotoxic T lymphocytes is now in progress. Conclusions: Combination therapy with gemcitabine and epitope peptides derived from VEGFR was well tolerated and the optimal dose for further clinical trials might be 3 mg/body. No significant financial relationships to disclose.