Treatment of stage IIIb/IV nonsmall cell lung can

Authors: ShengBin Shi RongHang Hu JieLin Qi XiaoYong Tang Jing Tian Rui Li ChunXiao Chang

Publish Date: 2013/04/11

Volume: 30, Issue: 2, Pages: 550-

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Abstract

To determine the efficacy and toxicity of Pemetrexed plus Oxaliplatin in patients suffering from stage IIIb or IV lung adenocarcinoma and being treated with Erlotinib as secondline treatment a total of 45 patients were randomly divided into two groups One group was treated with 500 mg/m2 Pemetrexed plus 100 mg/m2 Oxaliplatin and the other was treated with 500 mg/m2 Pemetrexed plus 75 mg/m2 Cisplatin All drugs were administered on day one of a 21day cycle In the Oxaliplatin group 3 patients 136  experienced partial response PR 9 patients 410  showed stable disease SD and 10 patients 455  had progressive disease PD In the Cisplatin group 2 patients 87  experienced PR 7 patients 304  showed SD and 14 patients 609  had PD The PFS of the Oxaliplatin group and the Cisplatin group was 445 months 95  CI 410–480 and 396 months 95  CI 368–424 P = 003 respectively The median overall survival OS was 108 months 95  CI 102–115 and 107 months 95  CI 102–113 P = 072 respectively There was no statistically significant difference in the occurrence rate of grades 3 and 4 myelotoxicity between the two groups However there was a significant difference in the occurrence rate of grades 3 and 4 gastrointestinal reactions and peripheral neurotoxicity between the two groups P  005 A regime combining Pemetrexed and Oxaliplatin was marginally effective and well tolerated in patients with stage IIIb or IV lung adenocarcinoma who have received Erlotinib as secondline treatmentLung cancer is one of the major malignant diseases that threaten human health and is the leading cause of death among all cancer patients 1 Nonsmall cell lung cancer NSCLC accounts for about 80  of all forms of lung cancer Over twothird of NSCLC cases are diagnosed in the advanced stage 2 Currently comprehensive treatments including chemotherapy and targeted drug therapies are the major therapies for advanced NSCLC Doublet chemotherapies consisting of platinum plus one of the thirdgeneration agents have become the standard regime 3 Different platinumbased chemotherapy doublets which have similar levels of efficacy are the firstline chemotherapies for patients with good performance 4 Consequently the current treatment guidelines recommend 4–6 cycles of chemotherapy For the secondline treatment EGFR–TKI monotherapy tended to be more effective in East Asian patients in terms of PFS and ORR compared with standard secondline chemotherapy and was associated with less toxicity and better tolerability 5 6 7 However it is unclear how to treat patients with disease progression or drug resistance after targeted therapy which has become a hot research fieldPemetrexed is an antifolate agent with multiple targets It inhibits the activities of several enzymes that are involved in purine and pyrimidine synthesis In elderly NSCLC patients promising results have been obtained when Pemetrexed is used in both firstline and maintenance therapies For example the efficacy and safety of Pemetrexed treatment have been evaluated in elderly patients with advanced nonsquamous NSCLC and a performance status of 0–1 Data from largescale randomized studies have been retrospectively analyzed for patients aged younger than 65 and older than 65 And it has been shown that the safety and efficacy are similar between two groups 8Oxaliplatin also named diaminocyclohexane oxalatoplatinum is a thirdgeneration platinum analogue that inhibits DNA replication It belongs to a distinct family of platinum compounds 9 Several randomized studies have suggested that Oxaliplatinbased doublets exert antitumor activities that are as effective as those of Cisplatin or Carboplatinbased regimes 10 11 In a phase III study the efficacy and tolerability of Gemcitabine and Oxaliplatin GEMOX with Paclitaxel and Carboplatin PCb in chemotherapynaive patients with stage IIIb/IV NSCLCs have been compared and it has been shown that the PFS OS and objective response rate of GEMOX are similar to those of PCb 12 In a one experience the combination of Pemetrexed Oxaliplatin and Bevacizumab has been well tolerated and has promising activity as a firstline therapy in random patients with stage IV nonsquamous NSCLC The objective response rate is 553  95  CI 395–711 The median PFS and OS are 62 95  CI 54–90 and 146 95  CI 98–195 months respectively 13 Misset et al 14 have shown that the combination of Pemetrexed and Oxaliplatin can be administered every 21 days using full therapeutic doses of each agent with acceptable tolerability and that the recommended dose for phase II studies is 500 mg/m2 Pemetrexed plus 120 mg/m2 Oxaliplatin in patients suffering from metastatic solid tumors The toxicity profile of Oxaliplatin particularly when compared with Cisplatin makes it an alternative treatment for patients unable to tolerate Cisplatin 15 In this study we evaluated the efficacy and safety of Pemetrexed plus Oxaliplatin and compared those with Pemetrexed plus Cisplatin in patients who have previously received Erlotinib

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