Predictive role of erythrocyte macrocitosys during treatment with pemetrexed in advanced non-small cell lung cancer patients
Menée à partir de données portant sur 191 patients atteints d'un cancer du poumon non à petites cellules de stade avancé (âge médian : 62 ans), cette étude évalue l'effet d'un traitement par pémétrexed sur l'évolution du volume globulaire moyen des érythrocytes, puis analyse la corrélation entre la survenue d'une macrocytose et la survie des patients
Objectives : Pemetrexed has been approved for the treatment of advanced non-small cell lung cancer (NSCLC) non-squamous histology, both as first- and second-line therapy. Pemetrexed is an antimetabolite drug, that inhibits enzymes involved in nucleotides bio-synthesis arresting cancer cells cycle. The aim of this study was the evaluation of the impact of pemetrexed on erythrocyte mean corpuscolar volume (MCV) change and its possible correlation with disease control rate (DCR), progression-free (PFS) and overall survival in NSCLC patients.
Materials and methods : A retrospective collection of clinical and laboratory data (including basal MCV and maximum MCV occurred during therapy) in advanced NSCLC patients treated with pemetrexed at seven Italian centres was performed. Nonparametric tests, univariate and multivariate analisys were used to assess correlation between variables and to identify predictors of outcomes.
Results : 191 patients were enrolled: median age 62, 60% male, 61% performance status (PS) 0, 91% stage IV, 88% adenocarcinoma histotype, 25% never smoker, 62% received pemetrexed as first-line. Mean MCV significantly increased from basal (89 fL) to during treatment (94 fL), with mean
ΔMCV = 4 fL. The median time from therapy start to maximum MCV was 2.2 months. Median PFS was 7 [CI95% 6-8] and 3 [CI95% 2-4] months [p = 0.0016], and median survival was 17 [CI95% 12-23] and 10 [CI95% 8-12] months [p = 0.02], in patients with ΔMCV > 5 fL (n = 80) and ΔMCV
≤ 5 fL (n = 111), respectively. Multivariate analysis identified age ≥ 62, PS 0, adenocarcinoma histology and
ΔMCV > 5 fL as independent predictors of longer PFS. A ΔMCV > 5 fL significantly correlates with DCR.
Conclusion
:
Pemetrexed induces macrocitosys. ΔMCV > 5 fL on pemetrexed therapy correlated with better DCR, PFS and OS. These results deserve further validation in prospective studies.
Lung Cancer , résumé, 2014