title: Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience.
abstract: BACKGROUND
  The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.
  
  
  METHODS
  Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.
  
  
  RESULTS
  Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).
  
  
  CONCLUSIONS
  Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.
authors.affiliation: Medical Oncology Department, Istituto Oncologico Veneto, Via Gattamelata 64, I-35128 Padua, Italy. giulia.pasello@ioveneto.it
authors.forename: Giulia
authors.initials: G
authors.lastname: Pasello
authors.forename: Samuele
authors.initials: S
authors.lastname: Nicotra
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Marulli
authors.forename: Federico
authors.initials: F
authors.lastname: Rea
authors.forename: Laura
authors.initials: L
authors.lastname: Bonanno
authors.forename: Paolo
authors.initials: P
authors.lastname: Carli
authors.forename: Cristina
authors.initials: C
authors.lastname: Magro
authors.forename: Antonio
authors.initials: A
authors.lastname: Jirillo
authors.forename: Adolfo
authors.initials: A
authors.lastname: Favaretto
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D008875:Middle Aged; D009367:Neoplasm Staging; D000068437:Pemetrexed; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D013921:Thrombocytopenia / Q000209:etiology; D000093542:Gemcitabine
chemical_list: D005971:Glutamates; D017671:Platinum Compounds; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D016190:Carboplatin; D000093542:Gemcitabine