For first line unresectable pleural mesothelioma, NCCN recommends: Alimta and carboplatin or cisplatin every 3 weeks as a Category 1 recommendation. In various studies, these combinations obtained overall response rate of 26.3% in 745 mesothelioma patients, and the combination of pemetrexed and carboplatin was associated with an overall response rate of 21.6%. One-year survival rate was 63 to 64%. The researchers’ findings were derived from an analysis of outcome data on 1,704 chemotherapy-naive patients.
NCCN also advises gemcitabine/cisplatin or Alimta or vinorelbine as a single agent . It also now recommends pemetrexed/cisplatin/bevacizumab followed by maintenance bevacizumab as a first‐line treatment option for patients with unresectable malignant pleural mesothelioma. This is a category 2A recommendation.
In a Phase III randomized, open-label trial, Avastin in combination with pemetrexed and cisplatin (CP) followed by Avastin maintenance significantly improved the primary outcome measure of median overall survival by 2.75 months from 16.07 to 18.82 months (stratified HR=0.76, 95%CI [0.61-0.94], p=0.0127) vs. CP alone in chemotherapy-naive malignant pleural mesothelioma patients. Progression-free survival was also significantly improved in the Avastin arm by 2 months from 7.48 to 9.59 months (stratified HR=0.61; 95%CI [0.50-0.75].
Substituting carboplatin is supported by peer-reviewed medical literature: Santoro et al and Razak et al.
Zalcman G, Mazières J, Margery J, et al. Bevacizumab 15mg/kg plus cisplatinpemetrexed (CP) triplet versus CP doublet in Malignant Pleural Mesothelioma (MPM): Results of the IFCTGFPC0701 MAPS randomized phase 3 trial [abstract]. J Clin Oncol 2015; 33:Abstract 7500.
Santoro A1, O’Brien ME, Stahel RA, Nackaerts K, Baas P, Karthaus M, Eberhardt W, Paz-Ares L, Sundstrom S, Liu Y, Ripoche V, Blatter J, Visseren-Grul CM, Manegold C. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program.J Thorac Oncol. 2008 Jul;3(7):756-63.
Kindler HL, Karrison TG, Gandara DR, et al. Multicenter, double-blind, placebo-controlled, randomized phase II trial of gemcitabine/cisplatin plus bevacizumab or placebo in patients with malignant mesothelioma. J Clin Oncol 2012;30:2509-2515.
Ceresoli GL, Zucali PA, Mencobono M, et al. Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma. Br J Cancer. 2013 Aug 6;109(3):552-8. doi: 10.1038/bjc.2013/bjc.2013.368. Epub 2013 Jul 16. 3. Dowell JE, Dunphy FR, Taub RN, et al. A multicenter, phase II study of cisplatin, pemetrexed and bevacizumab in patients with advanced malignant mesothelioma. Lung Cancer. 2012 Sep;77(3):567-71.
doi:10.1016/j.lungcan.2012.05.111. Epub 2012 Jul 4. 4. Jackman DM, Kindler HL, Yeap BY, et al. Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma. Cancer. 2008 Aug 15;113(4):808-14: 10.1002/cncr.23617
NCCN, MPM-B, 1 2016
Santoro A, O’Brien ME, Stahel RA, Nackaerts K, Baas P, Karthaus M, Eberhardt W, Paz-Ares L, Sundstrom S, Liu Y, Ripoche V, Blatter J, Visseren-Grul CM, Manegold C. Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. J Thorac Oncol. 2008 Jul;3(7):756-63.
Li L, Razak AR, Hughes A. Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: A realistic treatment option? Lung Cancer. 2008 Oct 14.
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