title: Predictive role of erythrocyte macrocytosis during treatment with pemetrexed in advanced non-small cell lung cancer patients.
abstract: OBJECTIVE
  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 corpuscular volume (MCV) change and its possible correlation with disease control rate (DCR), progression free (PFS) and overall survival (OS) in NSCLC patients.
  
  
  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 centers was performed. Nonparametric tests, univariate and multivariate analysis 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 (89fL) to during treatment (94fL), with mean ΔMCV=4fL. 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>5fL (n=80) and ΔMCV≤5fL (n=111), respectively. Multivariate analysis identified age ≥62, PS 0, adenocarcinoma histology and ΔMCV>5fL as independent predictors of longer PFS. A ΔMCV>5fL significantly correlates with DCR.
  
  
  CONCLUSIONS
  Pemetrexed induces macrocytosis. ΔMCV>5fL on pemetrexed therapy correlated with better DCR, PFS and OS. These results deserve further validation in prospective studies.
authors: Oncology Unit, University Hospital of Parma, Parma, Italy. Electronic address: sebabuti@libero.it.
authors: Sebastiano
authors: S
authors: Buti
authors: Oncology Unit, University Hospital of Parma, Parma, Italy.
authors: Paola
authors: P
authors: Bordi
authors: Oncology Unit, University Hospital of Parma, Parma, Italy.
authors: Marcello
authors: M
authors: Tiseo
authors: Oncology Unit, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Emilio
authors: E
authors: Bria
authors: Biostatistics Unit, Regina Elena National Cancer Institute, Roma, Italy.
authors: Isabella
authors: I
authors: Sperduti
authors: Clinical Trials Unit, Istituto Nazionale dei Tumori Fondazione 'G. Pascale' - IRCCS, Napoli, Italy.
authors: Massimo
authors: M
authors: Di Maio
authors: Oncology Unit, Azienda Istituti Ospitalieri di Cremona, Cremona, Italy.
authors: Stefano
authors: S
authors: Panni
authors: Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria "San Luigi Gonzaga", Orbassano, Torino, Italy.
authors: Silvia
authors: S
authors: Novello
authors: Department of Oncology, University of Turin, Azienda Ospedaliero-Universitaria "San Luigi Gonzaga", Orbassano, Torino, Italy.
authors: Simonetta Grazia
authors: SG
authors: Rapetti
authors: Oncology Unit, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Sara
authors: S
authors: Pilotto
authors: Department of Oncology, AUSL Rimini, Cervesi Hospital, Cattolica (RN), Italy.
authors: Giovenzio
authors: G
authors: Genestreti
authors: Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy.
authors: Antonio
authors: A
authors: Rossi
authors: Oncology Day Hospital, Guastalla Hospital, AUSL of Reggio Emilia, Italy.
authors: Debora
authors: D
authors: Pezzuolo
authors: Oncology Unit, University Hospital of Parma, Parma, Italy.
authors: Roberta
authors: R
authors: Camisa
authors: Oncology Unit, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors: Giampaolo
authors: G
authors: Tortora
authors: Oncology Unit, University Hospital of Parma, Parma, Italy.
authors: Andrea
authors: A
authors: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D004909:Erythrocyte Indices; D004913:Erythrocytes, Abnormal / Q000473:pathology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068437:Pemetrexed
keywords: Macrocytosis; Mean corpuscular volume; Non-small cell lung cancer; Pemetrexed; Predictive role; Prognostic