PMID- 21586625
OWN - NLM
STAT- MEDLINE
DCOM- 20111024
LR  - 20220330
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 13
DP  - 2011 Jul 1
TI  - Telomerase peptide vaccination combined with temozolomide: a clinical trial in 
      stage IV melanoma patients.
PG  - 4568-80
LID - 10.1158/1078-0432.CCR-11-0184 [doi]
AB  - PURPOSE: 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. EXPERIMENTAL DESIGN: Twenty-five subjects with advanced stage IV 
      melanoma (M1B or M1C) received concomitant temozolomide and GV1001. Temozolomide 
      was administered 200 mg/m(2) 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 IFNgamma/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.
FAU - Kyte, Jon Amund
AU  - Kyte JA
AD  - Section for Clinical Cancer Research, Department of Oncology, Oslo University 
      Hospital, Oslo, Norway. jon.amund.kyte@rr-research.no
FAU - Gaudernack, Gustav
AU  - Gaudernack G
FAU - Dueland, Svein
AU  - Dueland S
FAU - Trachsel, Sissel
AU  - Trachsel S
FAU - Julsrud, Lars
AU  - Julsrud L
FAU - Aamdal, Steinar
AU  - Aamdal S
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110517
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (Vaccines, Subunit)
RN  - 7GR28W0FJI (Dacarbazine)
RN  - EC 2.7.7.49 (Telomerase)
RN  - YF1K15M17Y (Temozolomide)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/*therapeutic use
MH  - Cancer Vaccines/*therapeutic use
MH  - Cytokines/biosynthesis
MH  - Dacarbazine/*analogs & derivatives/therapeutic use
MH  - Humans
MH  - Immunologic Memory
MH  - Melanoma/immunology/mortality/*pathology/*therapy
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Survival Analysis
MH  - T-Lymphocytes/immunology
MH  - *Telomerase/immunology
MH  - Temozolomide
MH  - Treatment Outcome
MH  - Vaccines, Subunit/*therapeutic use
MH  - Young Adult
EDAT- 2011/05/19 06:00
MHDA- 2011/10/25 06:00
CRDT- 2011/05/19 06:00
PHST- 2011/05/19 06:00 [entrez]
PHST- 2011/05/19 06:00 [pubmed]
PHST- 2011/10/25 06:00 [medline]
AID - 1078-0432.CCR-11-0184 [pii]
AID - 10.1158/1078-0432.CCR-11-0184 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Jul 1;17(13):4568-80. doi: 10.1158/1078-0432.CCR-11-0184. 
      Epub 2011 May 17.