title: Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program.
abstract: BACKGROUND
  In a randomized phase III trial, pemetrexed plus cisplatin was associated with improved survival compared with cisplatin alone for patients with malignant pleural mesothelioma (MPM). However, there are limited data available on the efficacy of these and other chemotherapy regimens in patients who have received previous systemic chemotherapy. To gather additional efficacy and safety data of pemetrexed/cisplatin and pemetrexed alone in previously treated patients, we examined patients treated on the Eli Lilly and Company expanded access program (EAP).
  
  
  METHODS
  Patients with malignant mesothelioma were enrolled in this trial. Of 1056 patients receiving at least one dose of the study drug, 187 (17.7%) were previously treated patients with MPM. Patients were treated every 21 days with pemetrexed 500 mg/m alone (n = 91) or in combination with cisplatin 75 mg/m (n = 96) for a maximum of six cycles. All patients received folic acid and vitamin B12 supplementation and steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmaco-vigilance database for all patients enrolled in the EAP.
  
  
  RESULTS
  Median age of the previously treated pleural mesothelioma subset was 66 years (range, 27-87 years). Based on 153 evaluable patients (a subset of the larger intent-to-treat population of 187), the overall response rate was 32.5% for pemetrexed and cisplatin and 5.5% for pemetrexed alone. The disease control rate (response rate + stable disease) was 68.7% for pemetrexed and cisplatin and 46.6% for pemetrexed alone. Median survival was 7.6 months for pemetrexed plus cisplatin (67% censored) and 4.1 months for pemetrexed alone (55% censored). The most commonly reported serious adverse events 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
  The data from this EAP study suggest that patients with previously treated MPM can benefit from treatment with pemetrexed alone or in combination with cisplatin. The treatment is associated with acceptable toxicity.
authors.affiliation: Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Pasi_Janne@dfci.harvard.edu
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
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: Zhishen
authors.initials: Z
authors.lastname: Ye
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Monberg
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001707:Biopsy, Needle; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020714:Maximum Tolerated Dose; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D010166:Palliative Care; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D012074:Remission Induction; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin