title: Phase II trial of pemetrexed disodium (ALIMTA, LY231514) in chemotherapy-naïve patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  To evaluate the efficacy and safety of pemetrexed therapy for chemotherapy-naïve patients with surgically incurable non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Eligible patients received pemetrexed 600 mg/m2 every 3 weeks. Restaging was performed after every two cycles of therapy and toxicity was assessed at each cycle of pemetrexed. In the absence of disease progression or undue toxicity, treatment was continued for a maximum of 12 cycles.
  
  
  RESULTS
  Fifty-nine patients (median age 59 years; range 39-74 years) received a median of four cycles of pemetrexed. Nineteen patients (32%) had a ECOG performance status (PS) of two and 39 patients (66%) had stage IV disease. The most common histological sub-types were adenocarcinoma (20 patients, 34%) and large cell (18 patients, 31%). Sixteen patients (27%) had received prior radiotherapy. Nine patients achieved a partial response for an overall response rate of 15.8% (95% confidence interval CI 7% to 28%). The median duration of response was 4.9 months, and the median survival was 7.2 months. The principal toxicities were myelosuppression and rash. While grade 3 or 4 neutropenia was seen in 25 patients (42%), only two patients (3%) developed grade 3 infection. Eighteen patients (31%) developed grade 3 or 4 cutaneous toxicity, which improved with prophylactic oral dexamethasone administered for 3 days beginning the day before pemetrexed treatment. Asymptomatic elevations in hepatic biochemistry (especially alanine transaminase and aspartate transaminase) were seen in 47 patients (80%); however, these did not interfere with the dose or schedule of pemetrexed and returned to normal levels throughout the study.
  
  
  CONCLUSIONS
  This is the largest study confirming the encouraging single-agent activity of pemetrexed in chemotherapy-naïve patients with NSCLC. In addition, this study demonstrates that a dose of 600 mg/m2 can be delivered safely; however, treatment should be restricted to patients with a PS of 0 or 1. The results of combination studies are awaited with interest.
authors.affiliation: Sydney Cancer Centre, Camperdown, NSW, Australia. sclarke@canc.rpa.cs.nsw.gov.au
authors.forename: S J
authors.initials: SJ
authors.lastname: Clarke
authors.forename: R
authors.initials: R
authors.lastname: Abratt
authors.forename: L
authors.initials: L
authors.lastname: Goedhals
authors.forename: M J
authors.initials: MJ
authors.lastname: Boyer
authors.forename: M J
authors.initials: MJ
authors.lastname: Millward
authors.forename: S P
authors.initials: SP
authors.lastname: Ackland
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care / Q000379:methods*; D000068437:Pemetrexed; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine