title: A phase II study of personalized peptide vaccination combined with gemcitabine for non-resectable pancreatic cancer patients.
abstract: We evaluated the safety of, and clinical and immune responses to personalized peptide vaccination with gemcitabine (GEM) as the first line therapy in patients with non-resectable pancreatic cancer. Pre-vaccination peripheral blood mononuclear cells (PBMCs) and plasma were prepared to examine cellular and humoral responses to 14 and 16 peptides in human leukocyte antigen (HLA)-A24+ or -A2+ patients, respectively. Only the reactive peptides (maximum of 4) were administered weekly at 3 mg/peptide. GEM was administered at 1000 mg/m(2) per week for 3 weeks, followed by 1 week of rest. Twenty-one patients with untreated and non-resectable pancreatic cancer were enrolled. The combination therapy was generally well tolerated. Boosting of cellular and humoral responses to the vaccinated peptides was observed in the post-vaccination (eighth) PBMCs and plasma from 14 of 18 and 13 of 18 patients tested, respectively. The best clinical responses were 7 cases of partial response, 9 cases of stable disease, and 5 cases of progressive disease. Median survival time of all 21 patients was 9.0 months (95% CI, 6-15.5 months) with a one year survival rate of 38%. Immune boosting in both cellular and humoral responses was well correlated with overall survival with a hazard ratio of 0.2 (95% CI, 0.06-0.73; log-rank p=0.0239). These results suggest a potential clinical benefit of this combination therapy for non-resectable pancreatic cancer patients as the first line therapy. Further exploration of this approach is warranted.
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yanagimoto
authors.forename: Hisanori
authors.initials: H
authors.lastname: Shiomi
authors.forename: Sohei
authors.initials: S
authors.lastname: Satoi
authors.forename: Takashi
authors.initials: T
authors.lastname: Mine
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Toyokawa
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tohru
authors.initials: T
authors.lastname: Tani
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.forename: A-Hon
authors.initials: AH
authors.lastname: Kwon
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007564:Japan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D019496:Cancer Vaccines; D006680:HLA Antigens; D022223:Vaccines, Subunit; D003841:Deoxycytidine; D000093542:Gemcitabine