title: An Open-Label, Randomized Phase II Trial of Personalized Peptide Vaccination in Patients with Bladder Cancer that Progressed after Platinum-Based Chemotherapy.
abstract: OBJECTIVE
  The prognosis of platinum-based chemotherapy-resistant metastatic urothelial cancer of the bladder remains poor. Personalized selection of the right peptides for each patient could be a novel approach for a cancer vaccine to boost anticancer immunity.
  
  
  METHODS
  In this randomized, open-label, phase II study, patients ages ≥18 years with progressive bladder cancer after first-line platinum-based chemotherapy were randomly assigned (1:1) to receive personalized peptide vaccination (PPV) plus best supportive care (BSC) or BSC. PPV treatment used a maximum of four peptides chosen from 31 candidate peptides according to human leukocyte antigen types and peptide-reactive IgG titers, for 12 s.c. injections (8 injections, weekly; 4 injections, bi-weekly). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), immune response, and toxicity.
  
  
  RESULTS
  Eighty patients were randomly assigned to receive either PPV plus BSC (n = 39) or BSC (n = 41). No significant improvement in PFS was noted [HR, 0.7; 95% confidence interval (CI), 0.4-1.2, P = 0.17]. For the secondary endpoints, PPV plus BSC significantly prolonged OS compared with BSC (HR, 0.58; 95% CI, 0.34-0.99, P = 0.049), with median OS of 7.9 months (95% CI, 3.5-12.0) in the PPV plus BSC and 4.1 months (95% CI, 2.8-6.9) in the BSC. PPV treatment was well tolerated, without serious adverse drug reactions.
  
  
  CONCLUSIONS
  PPV could not prolong PFS, but OS appeared to be improved with low toxicity and immune responses. Further large-scale, randomized trials are needed to confirm these results.
authors.affiliation: Divisions of Clinical Research, Kurume University School of Medicine, Kurume, Japan. Department of Urology, Kurume University School of Medicine, Kurume, Japan. noguchi@med.kurume-u.ac.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Urology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Uemura
authors.affiliation: Department of Urology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Arai
authors.affiliation: Department of Urology, Kumamoto University, Kumamoto, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Eto
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, University of Kyushu, Fukuoka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.affiliation: Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ohyama
authors.affiliation: Department of Urology, Okayama University Graduate School of Medicine, Okayama, Japan.
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Nasu
authors.affiliation: Department of Urology, Fukuoka University, Fukuoka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Fukuko
authors.initials: F
authors.lastname: Moriya
authors.affiliation: Department of Urology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Suekane
authors.affiliation: Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.affiliation: Kurume University School of Medicine, Kurume, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.affiliation: Cancer Vaccines, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Bio-Statistics Center, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kakuma
authors.affiliation: Cancer Vaccine Center, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003131:Combined Modality Therapy; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010984:Platinum / Q000008:administration & dosage; D019233:Retreatment; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D010984:Platinum