PMID- 22692758
OWN - NLM
STAT- MEDLINE
DCOM- 20130507
LR  - 20211203
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 61
IP  - 12
DP  - 2012 Dec
TI  - Analysis of pre-treatment markers predictive of treatment benefit for the 
      therapeutic cancer vaccine MVA-5T4 (TroVax).
PG  - 2283-94
LID - 10.1007/s00262-012-1302-9 [doi]
AB  - Cancer vaccines such as MVA-5T4 (TroVax((R))) must induce an efficacious immune 
      response to deliver therapeutic benefit. The identification of biomarkers that 
      impact on the clinical and/or immunological efficacy of cancer vaccines is 
      required in order to select patients who are most likely to benefit from this 
      treatment modality. Here, we sought to identify a predictor of treatment benefit 
      for renal cancer patients treated with MVA-5T4. Statistical modeling was 
      undertaken using data from a phase III trial in which patients requiring 
      first-line treatment for metastatic renal cell carcinoma were randomized 1:1 to 
      receive MVA-5T4 or placebo alongside sunitinib, IL-2 or IFN-alpha. Numerous 
      pre-treatment factors associated with inflammatory anemia (e.g., CRP, hemoglobin, 
      hematocrit, IL-6, ferritin, platelets) demonstrated a significant relationship 
      with tumor burden and patient survival. From these prognostic factors, the 
      pre-treatment mean corpuscular hemoglobin concentration (MCHC) was found to be 
      the best predictor of treatment benefit (P < 0.01) for MVA-5T4 treated patients 
      and also correlated positively with tumor shrinkage (P < 0.001). Furthermore, 
      MCHC levels showed a significant positive association with 5T4 antibody response 
      (P = 0.01). The latter result was confirmed using an independent data set 
      comprising phase II trials of MVA-5T4 in patients with colorectal, renal and 
      prostate cancers. Retrospective analyses demonstrated that RCC patients who had 
      very large tumor burdens and low MCHC levels received little or no benefit from 
      treatment with MVA-5T4; however, patients with smaller tumor burdens and normal 
      MCHC levels received substantial benefit from treatment with MVA-5T4.
FAU - Harrop, Richard
AU  - Harrop R
AD  - Oxford BioMedica (UK) Ltd, The Medawar Centre, Oxford Science Park, Oxford, OX4 
      4GA, UK. r.harrop@oxfordbiomedica.co.uk
FAU - Treasure, Peter
AU  - Treasure P
FAU - de Belin, Jackie
AU  - de Belin J
FAU - Kelleher, Michelle
AU  - Kelleher M
FAU - Bolton, Gemma
AU  - Bolton G
FAU - Naylor, Stuart
AU  - Naylor S
FAU - Shingler, William H
AU  - Shingler WH
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20120613
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Hemoglobins)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-2)
RN  - 0 (TroVax)
RN  - 0 (Vaccines, DNA)
SB  - IM
MH  - Anemia/immunology/metabolism
MH  - Antibodies, Neoplasm/immunology
MH  - Biomarkers, Tumor/*immunology/*metabolism
MH  - Cancer Vaccines/immunology/*therapeutic use
MH  - Carcinoma, Renal Cell/*drug therapy/immunology/metabolism
MH  - Hemoglobins/immunology/metabolism
MH  - Humans
MH  - Interferon-alpha/immunology/metabolism
MH  - Interleukin-2/immunology/metabolism
MH  - Kidney Neoplasms/*drug therapy/immunology/metabolism
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Retrospective Studies
MH  - Vaccines, DNA
PMC - PMC11029511
EDAT- 2012/06/14 06:00
MHDA- 2013/05/08 06:00
PMCR- 2012/06/13
CRDT- 2012/06/14 06:00
PHST- 2012/03/26 00:00 [received]
PHST- 2012/05/30 00:00 [accepted]
PHST- 2012/06/14 06:00 [entrez]
PHST- 2012/06/14 06:00 [pubmed]
PHST- 2013/05/08 06:00 [medline]
PHST- 2012/06/13 00:00 [pmc-release]
AID - 1302 [pii]
AID - 10.1007/s00262-012-1302-9 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2012 Dec;61(12):2283-94. doi: 
      10.1007/s00262-012-1302-9. Epub 2012 Jun 13.