title: Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.
abstract: BACKGROUND
  Pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM.
  
  
  METHODS
  From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. Gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity.
  
  
  RESULTS
  A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild.
  
  
  CONCLUSIONS
  The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors.
authors.affiliation: Department of Medical Oncology and Hematology, Humanitas Clinical Institute of Rozzano, Milan, Italy. paolo.zucali@humanitas.it
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Zucali
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: Isabella
authors.initials: I
authors.lastname: Garassino
authors.forename: Fabio
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Cavina
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Campagnoli
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: Silvia
authors.initials: S
authors.lastname: Salamina
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Soto Parra
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D014747:Vinblastine; D006147:Guanine; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine