Most
pancreatic cancer patients are diagnosed at the advanced stages, and no
therapy is superior to
gemcitabine alone. To confirm the feasibility and efficacy of a novel clinical intervention using
tumor vessel-specific anti-
angiogenic peptide vaccination, we conducted a clinical phase I/II trial using
HLA-A*2402/A*0201-restricted
vascular endothelial growth factor receptor type 1 (VEGFR1)-derived
peptide vaccination in combination with
gemcitabine for advanced
pancreatic cancer (http://www.clinical-trials.gov; NCT00683358 and NCT00683085). Four of the enrolled patients (n = 2 for
HLA-A*2402 and n = 2 for
HLA-A*0201 protocol, respectively), defined as having progressive disease according to the Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v.1.0), failed to respond to the
therapy. Another two patients enrolled in
HLA-A*2402 protocol dropped out of the study due to rapid
disease progression. Grade 2-3 hematologic toxicities were observed in all cases, but the treatment was well tolerated with minimal systemic adverse events. One case in
HLA-A*2402 protocol and another case in
HLA-A*0201 protocol suffered complicated gastrointestinal (GI)
bleeding during vaccination. The causal relationship between GI
bleeding and VEGFR1-peptide vaccination is unclear according to the pathologic examination. These studies terminated prematurely because of the advanced stage of the disease in the enrolled patients on entry to the study. Despite GI
bleeding,
peptide vaccination provides a feasible treatment option for many advanced
pancreatic cancer patients.