title: Second-line chemotherapy in malignant pleural mesothelioma: results of a retrospective multicenter survey.
abstract: The pemetrexed-cisplatin chemotherapy is standard of care in first-line (FL) treatment of malignant pleural mesothelioma (MPM). The second-line (SL) chemotherapy is considered, but the optimal treatment has not been defined yet. The aim of this study was to evaluate the clinical outcomes of SL-therapy in a series of MPM-patients included in a retrospective multicenter database. Clinical records of MPM-patients who received SL-treatment from 1996 to 2008 were reviewed. Study endpoints were response, overall-survival (OS), and progression-free-survival (PFS) for SL, stratified for patient characteristics, FL-outcomes, and type of SL. Out of 423 patients, 181 with full clinical data were identified. Patients' characteristics: median-age 64 years (range: 36-85); male gender 115 (63.5%); good EORTC-score 109 (60.2%); epithelial histology 135 (74.6%). After FL, 147 (81.2%) patients achieved disease-control (DC) and 45 had a time-to-progression≥12 months (TTP≥12). After SL, 95 patients (52.6%) achieved DC (21 response; 74 stable-disease); median PFS and OS were 4.3 and 8.7 months, respectively. According to multivariate analysis, DC after SL-therapy was significantly related to pemetrexed-based treatment (OR: 2.46; p=0.017) and FL-TTP≥12 (OR: 3.50; p=0.006). PFS was related to younger age (<65 years) (HR: 0.70; p=0.045), ECOG-PS0 (HR: 0.67; p=0.022), and FL-TTP≥12 (HR: 0.45; p<0.001). OS was significantly related to ECOG-PS0 (HR: 0.43; p<0.001) and to FL-TTP≥12 (HR: 0.54; p=0.005). In pemetrexed pre-treated patients, re-treatment with a pemetrexed/platinum combination significantly reduced the risk-of-death than pemetrexed alone (HR: 0.11; p<0.001). In conclusion, SL-chemotherapy seems to be active in MPM-patients, particularly in younger patients with ECOG-PS0 and prolonged TTP after FL-pemetrexed-based chemotherapy. In selected patients, re-challenge with pemetrexed-based regimens, preferentially associated with platinum-compound, appears to be an option for SL-setting. Considering the important limitations of this study, due to retrospective nature and the possible selection bias, prospective clinical trials are warranted to clarify these issues.
authors.affiliation: Department of Oncology, Humanitas Cancer Center, Rozzano, Italy. paolo.zucali@humanitas.it
authors.forename: P A
authors.initials: PA
authors.lastname: Zucali
authors.forename: M
authors.initials: M
authors.lastname: Simonelli
authors.forename: G
authors.initials: G
authors.lastname: Michetti
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
authors.forename: G L
authors.initials: GL
authors.lastname: Ceresoli
authors.forename: E
authors.initials: E
authors.lastname: Collovà
authors.forename: A
authors.initials: A
authors.lastname: Follador
authors.forename: M
authors.initials: M
authors.lastname: Lo Dico
authors.forename: A
authors.initials: A
authors.lastname: Moretti
authors.forename: F
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: E
authors.initials: E
authors.lastname: Lorenzi
authors.forename: M
authors.initials: M
authors.lastname: Perrino
authors.forename: L
authors.initials: L
authors.lastname: Giordano
authors.forename: G
authors.initials: G
authors.lastname: Farina
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: M
authors.initials: M
authors.lastname: Garassino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D000068437:Pemetrexed; D017671:Platinum Compounds / Q000627:therapeutic use; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D017671:Platinum Compounds; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin