title: Pemetrexed maintenance therapy in patients with malignant pleural mesothelioma.
abstract: OBJECTIVE
  To investigate the toxicity and effectiveness of pemetrexed maintenance therapy (PMT) in patients with malignant pleural mesothelioma (MPM).
  
  
  METHODS
  Eligible were patients with histologically proven advanced MPM, WHO PS 0-2 and adequate hematological, renal and hepatic function in whom during 6 courses of pemetrexed containing induction therapy no disease progression was observed. PMT, 500 mg/m intravenously on day 1 every 3 weeks, was continued until disease progression, unacceptable toxicity, or if continuation was considered to be not in the patient's best interest. Written informed consent was obtained from all patients.
  
  
  RESULTS
  Of the 27 patients who received induction therapy, 13 were treated with PMT. The median number of PMT courses was 4 (range = 2 to 14). No grade 4 toxicity was observed. Grade 3 neutropenia, leucopenia and anemia occurred 15%, 8% and 8%, respectively. The only non-hematological grade 3 toxicity during PMT was fatigue (15%). During PMT creatinine clearance decreased from 88 (+/-21) ml/min to 77 (+/-26) ml/min (p < 0.05). The reason to stop PMT was disease progression (69%), toxicity (23%) and in patient's best interest (8%). During PMT 23% of the patients with stable disease after induction therapy achieved a partial response. Time to progression and overall survival were 3.4 and 6.0 months versus 8.5 and 17.9 months, respectively (p < 0.0001).
  
  
  CONCLUSIONS
  PMT in MPM patients is non-toxic, well tolerated and although promising effects on TTP and OS are demonstrated, the effectiveness of PMT should be further explored in a prospective randomized clinical trial.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC-Daniel den Hoed Cancer Clinic, Rotterdam, The Netherlands.
authors.forename: Debby P M
authors.initials: DP
authors.lastname: van den Bogaert
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Pouw
authors.forename: Gerda
authors.initials: G
authors.lastname: van Wijhe
authors.forename: René M
authors.initials: RM
authors.lastname: Vernhout
authors.forename: Veerle F M
authors.initials: VF
authors.lastname: Surmont
authors.forename: Henk C
authors.initials: HC
authors.lastname: Hoogsteden
authors.forename: Rob J
authors.initials: RJ
authors.lastname: van Klaveren
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009426:Netherlands / Q000453:epidemiology; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase