title: A randomized phase II trial evaluating standard (50 mg/min) versus low (10 mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy.
abstract: OBJECTIVE
  Gemcitabine is one of the most active drugs against non-small-cell lung cancer (NSCLC). Preclinical data suggested that gemcitabine efficacy could be improved by increasing the dose or by increasing the infusion duration. This study has been designed in order to explore two different approaches of gemcitabine dose intensification in patients with advanced NSCLC.
  
  
  METHODS
  A total of 121 chemonaive patients with locally advanced or metastatic NSCLC not suitable for a platinum-based chemotherapy were randomly allocated to chemotherapy with gemcitabine 1500 mg/m2 on days 1 and 8 every 3 weeks by standard 30 min intravenous infusion (arm A), or gemcitabine 10 mg/m2/min for 150 min on days 1 and 8 every 3 weeks by intravenous infusion at fixed dose rate (arm B).
  
  
  RESULTS
  One hundred and seventeen patients were fully analyzed. No difference in response rate (16.1% versus 9.9%, p=0.28), median time to disease progression (4 months versus 4.5 months, p=0.34) median survival (9.8 months in both arms), and 1-year survival (42.6% versus 39.0% p=0.98) was detected in arms A and B, respectively. No treatment-related deaths occurred. Main hematological toxicities were grade 3-4 neutropenia observed in 17.9% of patients in group A and in 49.2% of individuals in group B (p=0.0002). The incidence of febrile neutropenia was 3.3% in arm A and 0% in arm B (p=0.17). Grade 3-4 thrombocytopenia was more frequently observed in arm B patients (9.9% versus 1.8%, p=0.057). Non-hematological toxicity was similar in both arms, and consisted in grade 1-2 gastrointestinal toxicity observed in 48.2% of patients in arm A and 41.0% in arm B.
  
  
  CONCLUSIONS
  Intensification of standard doses or prolonged infusion schedule did not result in efficacy improvement. Gemcitabine infusion duration does not warrant further investigation in patients with advanced NSCLC.
authors.affiliation: Division of Medical Oncology, Bellaria Hospital, Bologna, Via Altura 3, 40139 Bologna, Italy. federico.cappuzzo@ausl.bo.it
authors.forename: F
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: S
authors.initials: S
authors.lastname: Novello
authors.forename: F
authors.initials: F
authors.lastname: De Marinis
authors.forename: G
authors.initials: G
authors.lastname: Selvaggi
authors.forename: G V
authors.initials: GV
authors.lastname: Scagliotti
authors.forename: F
authors.initials: F
authors.lastname: Barbieri
authors.forename: M
authors.initials: M
authors.lastname: Maur
authors.forename: M
authors.initials: M
authors.lastname: Papi
authors.forename: E
authors.initials: E
authors.lastname: Pasquini
authors.forename: S
authors.initials: S
authors.lastname: Bartolini
authors.forename: L
authors.initials: L
authors.lastname: Marini
authors.forename: L
authors.initials: L
authors.lastname: Crinò
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine