The role of maintenance pemetrexed in the treatment of non-small-cell lung cancer

Abstract

Until recently, the weight of evidence has supported the discontinuation of chemotherapy in advanced non-small-cell lung cancer (NSCLC) after 4-6 cycles of induction therapy. This allows patients with limited life expectancy a "treatment holiday." A minority of cases then go on to receive second-line therapy, although many deteriorate rapidly and never receive further active treatment. There has been renewed interest in the concept of maintenance from trials with pemetrexed and erlotinib. Both these agents can be given for long periods without serious cumulative toxicity in most patients. Both trials have shown significant extension of progression free survival in placebo-controlled trials. In cases who are not receiving pemetrexed as induction therapy, a statistically significant 5-month prolongation of overall survival in nonsquamous NSCLC has been reported. Treatment was well tolerated. This effect may reflect the early administration of an active second-line agent and it remains to be seen whether similar benefits will accrue to patients having pemetrexed as induction therapy. Keywords: inoperable NSCLC, chemotherapy, targeted treatments Treatment of advanced non-small-cell lung cancerThe majority of patients with non-small-cell lung cancer (NSCLC) present with inoperable metastatic or advanced disease at the time of diagnosis. With the 5-year survival rate ranging from 8% to 15%, the prognosis for many of the patients with advanced or metastatic NSCLC is poor.1 For patients with good performance status (PS), palliative systemic chemotherapy with platinum regimens offers modest life extension and improves quality of life. A meta-analysis in 1995 analyzed individual data from 9,387 patients in 52 clinical trials and confirmed the benefit of chemotherapy. 2The authors updated this meta-analysis in 2008 using data from 2,714 patients from 16 randomized clinical trials including newer chemotherapy regimens.3 Chemotherapy proved to reduce the risk of death by 13% (hazard ratio [HR] = 0.87; P = 0.005) 2 and increase the survival by 9% at 12 months translating to absolute survival benefit of 1.5 months. 3Adding a second active agent such as paclitaxel, docetaxel, gemcitabine, or vinorelbine to cisplatin has shown survival benefit over single-agent treatment, cisplatin. Addition of second agent proved to have superior response and survival rate over single-agent therapy in a meta-analysis conducted by Delbaldo et al 4 in 2004 that included 13,601 patients from 65 trials.Several platinum-based doublet therapies incorporating agents such as gemcitabine, docetaxel, paclitaxel, vinorelbine, or more recently pemetrexed for NSCLC of nonsquamous histology have become available. There have been several attempts Lung Cancer: Targets and Therapy downloaded from https: //www.dovepress.com/ by 54.245.55.244 on 12-May-2018 For personal use only.

Pemetrexed Disodium Heptahydrate Induces Apoptosis and Cell-cycle Arrest in Non-small-cell Lung Cancer Carrying an EGFR Exon 19 Deletion

“…For advanced NSCLC and locally advanced NSCLC treatment, pemetrexed is currently combined with cisplatin or carboplatin as a firstline treatment (3). In addition, pemetrexed is also used as a single drug in second-line therapy for maintenance therapy after platinum chemotherapy (3,4).…”