title: Phase I clinical trial of a peptide vaccine combined with tegafur-uracil             plus leucovorin for treatment of advanced or recurrent colorectal cancer.
abstract: Recently, analysis of tumor antigens using micro-arrays has revealed upregulation             of cancer-testis antigens RNF43 and TOMM34 and vascular endothelial growth factor             receptors VEGFR1 and VEGFR2 in colorectal cancer. A phase I clinical trial of             peptide vaccine therapy together with oral anticancer drugs was conducted to treat             advanced colorectal cancer using synthesized peptides of these tumor antigens             in order to confirm the safety, immunogenicity and activity of this treatment.             The subjects were patients with a human leukocyte antigen (HLA) type of A2402             who had inoperable colorectal cancer but had failed to respond to or were unable             to undergo standard chemotherapy. Four peptides (RNF43, TOMM34, VEGFR1 and VEGFR2)             were emulsified with incomplete Freund's adjuvant (Montanide), and the resulting             solution was administered subcutaneously once a week. Patients received the oral             anticancer drug tegafur-uracil plus leucovorin for four weeks continuously as             part of one course followed by one week of rest. The primary endpoint of the trial             was observation of adverse events as determined by the NCI-CTCAE criteria, and             the secondary endpoints were the size of the tumor and the number of cytotoxic             T lymphocytes (CTLs) in the peripheral blood after treatment. Vaccine therapy             was administered 148 times to 10 patients from July 2008 to December 2009. The             adverse events were grade 1 redness and induration, a grade 2 skin ulcer at the             vaccination site and grade 1 pyrexia. All patients tolerated treatment. Tumor             imaging revealed that after 1 course of treatment 1 patient had partial response             (PR), 7 had stable disease (SD) and 2 had progressive disease. A CTL assay of             10 patients revealed an increase in peptide-specific CTLs in patients with PR             and SD, and the clinical responses of those patients were observed. Kaplan‑Meier             analysis indicated that patients who had a strong CTL reaction had a tendency             to have longer progression‑free survival and overall survival.
authors: Department of Surgery, Institute of Gastroenterology, Tokyo Women's                     Medical University, Tokyo, Japan.
authors: Norimasa
authors: N
authors: Matsushita
authors: Atsushi
authors: A
authors: Aruga
authors: Yuji
authors: Y
authors: Inoue
authors: Yoshihito
authors: Y
authors: Kotera
authors: Kazuyoshi
authors: K
authors: Takeda
authors: Masakazu
authors: M
authors: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D015179:Colorectal Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin