title: The MILES-2G phase 2 study of single-agent gemcitabine with prolonged constant infusion in advanced non-small cell lung cancer elderly patients.
abstract: BACKGROUND
  Gemcitabine has been widely studied in elderly patients affected by advanced non-small cell lung cancer (NSCLC). A prolonged constant infusion (10 mg/m2/min) has been proposed as a way to improve its efficacy. Aim of this study is to describe activity and toxicity of single-agent gemcitabine given as prolonged infusion in the treatment of elderly patients with advanced NSCLC.
  
  
  METHODS
  Patients aged 70 years or older, with stage IV or IIIB (effusion/supraclavicular nodes) NSCLC, good performance status (0 or 1 according to ECOG classification) who had never received chemotherapy were eligible. Gemcitabine was administered at the dose of 1200 mg/m2 by prolonged infusion (10 mg/m2/min) on days 1 and 8 of each cycle. Courses were repeated every 21 days, for a maximum of 6 cycles, unless disease progression or severe toxicity. A single stage phase 2 design was applied, with 51 patients required to estimate a 25% +/- 10% response rate. Ten responses were required to define the treatment as active.
  
  
  RESULTS
  Fifty-one patients were enrolled, with a median age of 76 years (range 70-83). Two complete responses and seven partial responses were observed, for an overall response rate of 17.6% (95% exact C.I.: 8.4-30.9%). The median time to disease progression was 16.1 weeks (95% C.I.: 11.1-20.6) and the median overall survival was 41.3 weeks (95% C.I.: 27.6-50.6). There were 2 toxic deaths, due to bleeding and liver toxicity, and one patient had an ischemic stroke. Other non-haematological toxicities were: fatigue (44% of patients), grade 2-3 pulmonary toxicity (8%), grade 2-3 hepatic toxicity (16%). Nausea and stomatitis were mild and no cases of cardiac toxicity were observed. Haematological toxicity was mild, with no case of febrile neutropenia.
  
  
  CONCLUSIONS
  Gemcitabine at prolonged constant infusion produced a response rate lower than that required by study design and should no longer be of interest for the treatment of elderly patients with advanced NSCLC.
authors.affiliation: Medical Oncology, S. Giuseppe Moscati Hospital, Avellino, Italy. cgridelli@libero.it
authors.forename: Cesare
authors.initials: C
authors.lastname: Gridelli
authors.forename: Ermelinda
authors.initials: E
authors.lastname: De Maio
authors.forename: Santi
authors.initials: S
authors.lastname: Barbera
authors.forename: Mirella
authors.initials: M
authors.lastname: Sannicolo
authors.forename: Elena
authors.initials: E
authors.lastname: Piazza
authors.forename: FrancoVito
authors.initials: F
authors.lastname: Piantedosi
authors.forename: Luigi
authors.initials: L
authors.lastname: Brancaccio
authors.forename: Alessandro
authors.initials: A
authors.lastname: Morabito
authors.forename: Paolo
authors.initials: P
authors.lastname: Maione
authors.forename: Francesco
authors.initials: F
authors.lastname: Renda
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Signoriello
authors.forename: Francesco
authors.initials: F
authors.lastname: Perrone
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; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine