title: Telomerase peptide vaccination combined with temozolomide: a clinical trial in stage IV melanoma patients.
abstract: OBJECTIVE
  The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001. Our previous GV1001 trials showed immune responses in approximately 60% of lung or pancreatic cancer patients.
  
  
  METHODS
  Twenty-five subjects with advanced stage IV melanoma (M1B or M1C) received concomitant temozolomide and GV1001. Temozolomide was administered 200 mg/m² orally for 5 days every fourth week, and GV1001 as eight injections over 11 weeks. Immune response was evaluated by delayed type hypersensitivity, T-cell proliferation, and cytokine assays. The immunologic responders continued monthly vaccination.
  
  
  RESULTS
  The treatment was well tolerated. A GV1001-specific immune response was shown in 18 of 23 evaluated subjects (78%). Patients developing long-term T-cell memory survived more than those rapidly losing their responses. The immune response exhibited several characteristics of possible clinical significance including high IFNγ/IL-10 ratios, polyfunctional cytokine profiles, and recognition of naturally processed antigens. Survival compared favorably with matched controls from a benchmark meta-analysis (1 year: 44% vs. 24%, 2 years: 16% vs. 6.6%). The clinical responses developed gradually over years, contrary to what is expected from chemotherapy. Five patients developed partial tumor regression and six more recorded stable disease. One patient has no remaining disease on fluorodeoxyglucose positron emission tomography scans after 5 years.
  
  
  CONCLUSIONS
  The immunologic response rate is considerable compared with previous GV1001 trials without concomitant chemotherapy, although low toxicity is retained. The results warrant further studies of GV1001/temozolomide treatment and support the general concept of combining cancer vaccination with chemotherapy.
authors.affiliation: Section for Clinical Cancer Research, Department of Oncology, Oslo University Hospital, Oslo, Norway. jon.amund.kyte@rr-research.no
authors.forename: Jon Amund
authors.initials: JA
authors.lastname: Kyte
authors.forename: Gustav
authors.initials: G
authors.lastname: Gaudernack
authors.forename: Svein
authors.initials: S
authors.lastname: Dueland
authors.forename: Sissel
authors.initials: S
authors.lastname: Trachsel
authors.forename: Lars
authors.initials: L
authors.lastname: Julsrud
authors.forename: Steinar
authors.initials: S
authors.lastname: Aamdal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007156:Immunologic Memory; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology; D019098:Telomerase / Q000276:immunology; D000077204:Temozolomide; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D016207:Cytokines; D022223:Vaccines, Subunit; D003606:Dacarbazine; D019098:Telomerase; D000077204:Temozolomide