Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort.
BACKGROUND
We report a survey of mesothelioma survival rates with insights into the survival benefit because of pemetrexed. We also studied a potential link between specific single nucleotide polymorphisms of transcobalamin II (TCII) gene and susceptibility to both asbestos and pemetrexed.


METHODS
Clinical and occupational data from 287 consecutive mesothelioma patients were collected from the north-east region of France (1989-2007). Blood or paired tumoral and normal samples were collected from the last 210 French patients to study the TCII single nucleotide polymorphisms at the codon 259 (quantitative polymerase chain reaction). Results were compared with those obtained from a group of 263 French control healthy subjects and to a group of 91 German mesothelioma patients. Patients' characteristics and genotypes results were statistically analyzed for significant correlations.


RESULTS
The mean overall patient's survival was 18.19 +/- 21.07 months. Pemetrexed increased the patients' survival by 50% (21.81 versus 16.99 months). The TCII allele Proline (Pro) was overrepresented into the mesothelioma cohort when compared with the controls (35 versus 19.77%). This also concerned German patients. The alleles Pro and Proline Arginine (ProArg) were more frequent among patients exposed to asbestos (p = 0.005, p < 0.001, respectively). The allele ProArg was associated with the longest survival while under pemetrexed (p = 0.007). No difference was found in the genotypes of patients untreated with pemetrexed.


CONCLUSIONS
Pemetrexed treatment is related to a survival increase in mesothelioma patients. The allele Pro seems overrepresented in mesothelioma patients. Those having the allele ProArg present a better outcome under pemetrexed.
Vlastos
Fotis
F
The Centre for Biological Resources of Nancy/U724 INSERM, Central Hospital, Nancy, France.
Hillas
Georgios
G
Vidal
Philippe
P
Lacomme
Stéphanie
S
Galateau-Sallé
Françoise
F
Vollmer
Ekkehard
E
Guzman-Costabel
Josune
J
Vignaud
Jean Michel
JM
Martinet
Nadine
N
D000368:Aged; D000483:Alleles; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001194:Asbestos; D015331:Cohort Studies; D005260:Female; D005602:France; D005838:Genotype; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D000068437:Pemetrexed; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015996:Survival Rate; D014155:Transcobalamins / Q000235:genetics; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D014155:Transcobalamins; D000068437:Pemetrexed; D001194:Asbestos; D006147:Guanine