PURPOSE: We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m2 IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m2 (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria. Health related quality of life (HRQOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module (QLQ-LC13). RESULTS:Two hundred fifty patients were randomized: 80% male; median age, 58 years; and WHO PS, 0, 1, 2 in 25, 62, and 13% of cases, respectively. There were no toxic deaths. The main grade 3 or 4 toxicities observed were neutropenia and emesis, reported twice as often in the combination arm. Among 213 patients with measurable disease, response rate was 13.6% (arm A) versus 23.6% (arm B; P = .056). No difference in HRQOL was observed on any of the scales. Median overall and 1-year survival in arms A and B were 8.8 (95% CI, 7.8 to 10.8) v 11.4 months (95% CI, 10.1 to 15), respectively, and 40% v 46%, respectively (P = .048). CONCLUSION: A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone. This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM, without harmful effect on HRQOL.
RCT Entities:
PURPOSE: We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m2 IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m2 (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria. Health related quality of life (HRQOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module (QLQ-LC13). RESULTS: Two hundred fifty patients were randomized: 80% male; median age, 58 years; and WHO PS, 0, 1, 2 in 25, 62, and 13% of cases, respectively. There were no toxic deaths. The main grade 3 or 4 toxicities observed were neutropenia and emesis, reported twice as often in the combination arm. Among 213 patients with measurable disease, response rate was 13.6% (arm A) versus 23.6% (arm B; P = .056). No difference in HRQOL was observed on any of the scales. Median overall and 1-year survival in arms A and B were 8.8 (95% CI, 7.8 to 10.8) v 11.4 months (95% CI, 10.1 to 15), respectively, and 40% v 46%, respectively (P = .048). CONCLUSION: A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone. This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM, without harmful effect on HRQOL.
Authors: A Scherpereel; P Astoul; P Baas; T Berghmans; H Clayson; P de Vuyst; H Dienemann; F Galateau-Salle; C Hennequin; G Hillerdal; C Le Pe'choux; L Mutti; J-C Pairon; R Stahel; P van Houtte; J van Meerbeeck; D Waller; W Weder Journal: Zhongguo Fei Ai Za Zhi Date: 2010-10
Authors: S Cedrés; M A Montero; E Zamora; A Martínez; P Martínez; L Fariñas; A Navarro; D Torrejon; A Gabaldon; S Ramon Y Cajal; E Felip Journal: Clin Transl Oncol Date: 2013-12-10 Impact factor: 3.405
Authors: Deepa Magge; Mazen S Zenati; Frances Austin; Arun Mavanur; Magesh Sathaiah; Lekshmi Ramalingam; Heather Jones; Amer H Zureikat; Matthew Holtzman; Steven Ahrendt; James Pingpank; Herbert J Zeh; David L Bartlett; Haroon A Choudry Journal: Ann Surg Oncol Date: 2013-12-10 Impact factor: 5.344
Authors: Stephanie R Rice; Yun R Li; Theresa M Busch; Michele M Kim; Sally McNulty; Andrea Dimofte; Timothy C Zhu; Keith A Cengel; Charles B Simone Journal: Photochem Photobiol Date: 2018-12-28 Impact factor: 3.421