Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort

Our plain-English summary of Survey and biological insights of pemetrexed-related therapeutic improvement in mesothelioma: The Nancy Centre of Biological Resources' Mesothelioma Cohort, by F. Vlastos, G. Hillas, P. Vidal, et al (Journal of Thoracic Oncology, 2009).

The study

• Authors: F. Vlastos, G. Hillas, P. Vidal, S. Lacomme, F. Galateau-Sallé, E. Vollmer, J. Guzman-Costabel, J.M. Vignaud, N. Martinet
• Journal: Journal of Thoracic Oncology
• Published: 2009;4(10):1259-63
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: 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.

In plain English

This study looked back at 287 consecutive French patients with mesothelioma recorded by a biobank in Nancy, north-east France, between October 1989 and January 2007. Asbestos exposure was recorded for 80.7% of the men and 30% of the women. The article does not name fiber types. Mean survival after diagnosis was 18.19 months, and neither asbestos exposure nor pleural plaques was found to predict survival. The 63 patients who received pemetrexed-containing chemotherapy had a mean survival of 21.81 months, versus 16.99 months for the others, a statistically significant difference. The authors noted this was not a clinical trial and that many factors may have influenced the difference. In 210 patients, the authors tested a variation in the transcobalamin II gene. The Pro genotype appeared in 35% of patients versus 19.77% of 263 healthy French controls, and Pro and ProArg were more frequent among asbestos-exposed patients. Among pemetrexed-treated patients, the ProArg group had the longest mean survival, 26.47 months. The authors concluded that pemetrexed offers a measurable survival gain, while noting their study groups were relatively small.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cohort survey of consecutive mesothelioma patients from a biobank, with survival analysis and a genetic comparison against healthy controls and German patients; the authors state it is not a clinical trial
• Who was studied: 287 consecutive French mesothelioma patients from north-east France (Nancy biobank), accrued October 1989 to January 2007 (234 men, 53 women). Gene testing was done in 210 of them. Comparison groups were 263 French healthy control subjects matched in age and sex, and 91 German mesothelioma patients with no clinical data.
• Exposure: Asbestos exposure, recorded with age of onset and duration (no fiber types or jobs specified). 205 of 287 patients (71.4%) were exposed: 189 men (80.7%) and 16 women (30%). The study also looked at treatment with a pemetrexed-containing chemotherapy regimen (63 patients, 21.95%) and at transcobalamin II gene variants at codon 259 (Pro, ProArg, Arg).
• Main results:
  • Mean overall survival of the whole cohort was 18.19 months (SD 21.07).
  • Survival was related to histology. Patients with atypical mesothelial hyperplasia or the epithelial type survived statistically longer than those with other subtypes.
  • Asbestos exposure was not found to predict survival (p printed as 0.51).
  • The presence of pleural plaques was not correlated with survival (p printed as 0.33).
  • Pemetrexed-treated patients had a statistically significantly longer survival: mean 21.81 months (SD 20.33), versus 16.99 months (SD 21.52) for patients not given a pemetrexed-containing regimen.
  • Transcobalamin II genotypes in French mesothelioma patients were ProArg 55%, Pro 35% and Arg 10%. In the 263 healthy controls they were ProArg 61.21%, Pro 19.77% and Arg 19.01%. The Pro percentage was significantly higher in patients than in controls.
  • Pro and ProArg genotypes were more frequent among asbestos-exposed patients.
  • The genotype profile of French patients did not differ from that of the 91 German mesothelioma patients (ProArg 53.61%, Pro 29.34%, Arg 16.3%).
  • Genotype was not correlated with overall survival in the cohort.
  • Among pemetrexed-treated patients, mean survival was 26.47 months (SD 24.11) for ProArg (n = 34), 18.54 months (SD 13.73) for Pro (n = 22) and 14 months (SD 8.72) for Arg (n = 4). This association was statistically significant (p printed as 0.007).
  • No correlation was found between genotype and survival among patients not treated with pemetrexed.
• The authors' conclusion: The authors concluded that pemetrexed offers a measurable survival gain to mesothelioma patients and that transcobalamin II genotype differs between healthy subjects and mesothelioma patients, with Pro more frequent in French and German patients. At least for the French patients, they concluded that those with ProArg had a better outcome under pemetrexed. They suggested the higher frequency of Pro and ProArg in asbestos-exposed patients 'may indicate a genetic predisposition'.
• Limitations the authors state:
  • The study groups were relatively small.
  • The study was not a clinical trial, so many factors may have influenced the pemetrexed survival finding.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Pemetrexed (Alimta), Mesothelioma.

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