title: Vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma.
abstract: BACKGROUND
  Pemetrexed-platinum chemotherapy is the standard first-line treatment of unresectable malignant pleural mesothelioma (MPM). At progression, patients are generally selected to experimental trials, when available, or, in every-day clinical practice, they are offered second-line chemotherapy. The optimal treatment has not yet been defined. The aim of this retrospective, single-center study was to evaluate the activity and toxicity of vinorelbine administered to a consecutive series of pemetrexed-pretreated MPM patients.
  
  
  METHODS
  Vinorelbine 25 mg/m(2) was administered intravenously as a single agent on days 1, 8 every three weeks, either as second-line (2L) or further-line (>2L) therapy. Treatment was repeated for a maximum of 6 cycles, until progression, or unacceptable toxicity.
  
  
  RESULTS
  Fifty-nine patients were included in this analysis. Vinorelbine was given to 34 patients as 2L, and to 25 as > 2L treatment. The median age was 69 years (range 45-80). Forty-two patients (71.2%) had a good EORTC prognostic score. Partial response was observed in 9 (15.2%) cases, stable disease in 20 (33.9%). The overall disease control rate (DCR) was 49.1%. Median progression-free survival (PFS) and overall survival (OS) were 2.3 and 6.2 months, respectively. ECOG performance status (PS) (HR(0 vs. 1-2) 0.50; 95%CI: 0.3-0.8; p = 0.014) and PFS ≥ 6 months following first-line (FL) chemotherapy (HR(FL-PFS>6 ms vs. <6 ms) 0.50; 95%CI: 0.3-0.9; p = 0.031) were significantly associated to OS in multivariate analysis. No difference was observed in terms of DCR, PFS, and OS in relation to age, histology, sex, line of vinorelbine therapy, or response to FL treatment. Hematological toxicity was acceptable, with grade 3/4 neutropenia occurring in 5 (8.4%) patients, and there were no cases of febrile neutropenia. The main non-hematological toxicities were grade 2 fatigue in 17 (28.8%) and constipation in 7 (11.8%) patients.
  
  
  CONCLUSIONS
  Vinorelbine was moderately active in pemetrexed-pretreated MPM patients, with an acceptable toxicity profile, particularly in patients with ECOG-PS0 and FL-PFS ≥ 6 months.
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy. Electronic address: paolo.zucali@humanitas.it.
authors: P A
authors: PA
authors: Zucali
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: M
authors: M
authors: Perrino
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: E
authors: E
authors: Lorenzi
authors: Department of Medical Oncology and Hematology, Istituto Humanitas Gavazzeni, Bergamo, Italy.
authors: G L
authors: GL
authors: Ceresoli
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: F
authors: F
authors: De Vincenzo
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: M
authors: M
authors: Simonelli
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: L
authors: L
authors: Gianoncelli
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: R
authors: R
authors: De Sanctis
authors: Biostatistic Unit, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: L
authors: L
authors: Giordano
authors: Department of Medical Oncology and Hematology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
authors: A
authors: A
authors: Santoro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D005971:Glutamates / Q000627:therapeutic use; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D014747:Vinblastine; D006147:Guanine; D000077235:Vinorelbine
keywords: Activity and toxicity; Chemotherapy; Malignant pleural mesothelioma; Pemetrexed-pretreated patients; Second or further-line; Vinorelbine