title: Single-arm, open label study of pemetrexed plus cisplatin in chemotherapy naïve patients with malignant pleural mesothelioma: outcomes of an expanded access program.
abstract: BACKGROUND
  An expanded access program (EAP) provided patient access to pemetrexed prior to its commercial availability. The current report consists of US patients in the EAP who had chemotherapy naïve pleural mesothelioma.
  
  
  METHODS
  Eligible patients had a histologic or cytologic diagnosis of malignant mesothelioma that was not amenable to curative treatment with surgery. Study treatment consisted of pemetrexed 500mg/m(2) in combination with cisplatin 75mg/m(2) once every 21 days. Vitamin B12, folic acid, and dexamethasone were administered as prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all patients enrolled in the EAP.
  
  
  RESULTS
  Of 1056 patients receiving at least one dose of pemetrexed in the EAP, 728 had chemotherapy naïve pleural mesothelioma. Median age of this group was 70 years (range 23-89 years) and 84% were male. Among 615 patients, overall response rate was 20.5%, including 12 complete responses (2.0%) and 114 partial responses (18.5%). An additional 290 patients (47.2%) had stable disease. Median survival for all 728 patients was 10.8 months (95% CI=9.8, 12.3; 60.3% censorship) and 1 year survival was 45.4%. The most commonly reported SAEs in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%).
  
  
  CONCLUSIONS
  In this large cohort, 67.7% of patients treated with first-line chemotherapy experienced a response or stable disease. Survival time and toxicity from this EAP were promising for this difficult-to-treat disease.
authors.affiliation: Eli Lilly and Company, Lilly Corporate Center, Drop Code 6831, Indianapolis, IN 46285, USA. cobasaju@lilly.com
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: Zhishen
authors.initials: Z
authors.lastname: Ye
authors.forename: Antoinette J
authors.initials: AJ
authors.lastname: Wozniak
authors.forename: Chandra P
authors.initials: CP
authors.lastname: Belani
authors.forename: Mary-Louise
authors.initials: ML
authors.lastname: Keohan
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Ross
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Polikoff
authors.forename: David M
authors.initials: DM
authors.lastname: Mintzer
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Monberg
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage*; D017326:Clinical Trials, Phase III as Topic; D016001:Confidence Intervals; D018450:Disease Progression; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin