title: Pemetrexed plus gemcitabine as first-line chemotherapy for patients with peritoneal mesothelioma: final report of a phase II trial.
abstract: OBJECTIVE
  Pemetrexed in combination with cisplatin is approved for the treatment of pleural mesothelioma and is active in malignant peritoneal mesothelioma (MPeM). Pemetrexed and gemcitabine are synergistic in preclinical models, but the activity of this combination in MPeM is unknown. This clinical study assessed safety and efficacy of pemetrexed plus gemcitabine in chemotherapy-naïve patients with MPeM.
  
  
  METHODS
  Treatment consisted of gemcitabine 1,250 mg/m(2) on days 1 and 8, and pemetrexed 500 mg/m(2) on day 8, administered immediately before gemcitabine. Treatment was repeated every 21 days for six cycles or until disease progression. All patients received folic acid, vitamin B(12), and dexamethasone supplementation. End points included tumor response, toxicity, time to disease progression (TTPD), and overall survival (OS). Disease control rate (DCR) was also calculated.
  
  
  RESULTS
  Twenty patients were enrolled between December 2002 and May 2004. The confirmed response rate was 15% (95% CI, 3.2% to 37.9%), with three patients experiencing a partial response. The DCR was 50% (95% CI, 27.2% to 72.8%). The most common grade 3 to 4 nonhematologic toxicities included fatigue (20%), constipation (10%), vomiting (10%), and dehydration (10%). Hematologic toxicities included grade 3 to 4 neutropenia (60%) and febrile neutropenia (10%). One patient death was attributed to treatment. Median TTPD and OS times were 10.4 months and 26.8 months, respectively.
  
  
  CONCLUSIONS
  The combination of pemetrexed plus gemcitabine was active in patients with MPeM with a notably high incidence of neutropenia. Median TTPD and OS seem promising. This regimen may provide an alternative to standard therapies, especially for patients who cannot tolerate a platinum-based regimen.
authors.affiliation: Thoracic Oncology Program and Experimental Therapeutics Program, H. Lee Moffitt Cancer Center and Research Institute, MRC-4W, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA. george.simon@moffitt.org
authors.forename: George R
authors.initials: GR
authors.lastname: Simon
authors.forename: Claire F
authors.initials: CF
authors.lastname: Verschraegen
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Langer
authors.forename: Afshin
authors.initials: A
authors.lastname: Dowlati
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.forename: Karen
authors.initials: K
authors.lastname: Kelly
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Kalemkerian
authors.forename: Anne M
authors.initials: AM
authors.lastname: Traynor
authors.forename: Guangbin
authors.initials: G
authors.lastname: Peng
authors.forename: John
authors.initials: J
authors.lastname: Gill
authors.forename: Coleman K
authors.initials: CK
authors.lastname: Obasaju
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D000093542:Gemcitabine