Second-line chemotherapy in malignant pleural mesothelioma: Results of a retrospective multicenter survey

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 75; no. 3; pp. 360 - 367
• Main Authors: Zucali, P.A, Simonelli, M, Michetti, G, Tiseo, M, Ceresoli, G.L, Collovà, E, Follador, A, Lo Dico, M, Moretti, A, De Vincenzo, F, Lorenzi, E, Perrino, M, Giordano, L, Farina, G, Santoro, A, Garassino, M
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ireland Ltd 01-03-2012; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cisplatin - administration & dosage; Disease control; Female; Glutamates - administration & dosage; Guanine - administration & dosage; Guanine - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; Male; Malignant pleural mesothelioma; Medical sciences; Mesothelioma - drug therapy; Mesothelioma - mortality; Middle Aged; Multivariate Analysis; Pemetrexed; Platinum Compounds - therapeutic use; Pleural Neoplasms - drug therapy; Pleural Neoplasms - mortality; Pneumology; Progression-free survival; Pulmonary/Respiratory; Re-treatment; Retrospective Studies; Second-line therapy; Survival Rate; Treatment Outcome; Tumors; Tumors of the respiratory system and mediastinum; Malignant pleural mesothelioma; Pemetrexed; Re-treatment; Progression-free survival; Disease control; Second-line therapy; Prognosis; Disease; Respiratory disease; Malignant tumor; Survival; Retrospective; Chemotherapy; Control; Survey; Treatment; Cancerology; Pleural disease; Cancer; Pneumology
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2011.08.011

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.