Track topics on Twitter Track topics that are important to you
Subjects, who are eligible for the study, will be treated with four cycles of carboplatin AUC of 5 IV and pemetrexed 500mg/m2 IV every 21 days +/- 2 days as per the standard of care. Subjects who have not progressed after four cycles by radiological assessment (partial response or stable disease) will receive single agent pemetrexed 500mg/m2 IV q 21 days +/- 2 days as maintenance therapy and as the standard of care until disease progression or subject cannot tolerate.
Metformin will be given as 500 mg pills starting on day 1 of chemotherapy. Starting dose will 500mg po bid (1000mg/day). If tolerating (see below for dose reduction), the dose will be escalated to 1000mg po qam and 500mg po qpm (1500mg/day) from days 8 to 14. If still tolerating, the dose will be escalated to 2 500mg pills twice a day for a total dose of 2000mg/day from days 15 until end of the study. This dose has been found to be safe in healthy controls and in subjects treated with chemotherapy.
Metformin, an oral biguanide agent used for the treatment of non-insulin-dependent diabetes mellitus, is now prescribed to more than 120 million people worldwide. Its glucose lowering effects result from both inhibition of liver gluconeogenesis and increased insulin sensitivity in peripheral tissue. Metformin has limited adverse effects with little or no risk of hypoglycemia in healthy, nondiabetic controls. In addition to its anti-diabetic properties, metformin has demonstrated both chemopreventative and therapeutic effects in both prostate and breast cancer.
The role of metformin as a preventative and therapeutic agent in lung cancer is beginning to be assessed. A recent epidemiological study from Taiwan demonstrated a 39-45% decreased risk of lung cancer in diabetic patients being treated with antidiabetic drugs including metformin versus those not taking these agents. These studies have triggered preclinical and clinical observational trials that further support metformin's potential as an antineoplastic agent. Two observational studies in humans have reinforced metformin's potential role as a therapeutic agent in lung cancer. In the first, Mezzone et al. showed that diabetic patients with lung cancer previously treated with metformin or thiazolidinediones had a lower incidence of metastatic disease at the time of diagnosis and a reduced risk of death compared to those who did not receive the same treatment. More recently, a retrospective study performed by Tan et al. evaluated the outcomes of three groups of diabetic patients with NSCLC treated with first line chemotherapy and receiving various diabetic drugs. In this study, patients treated with chemotherapy with metformin had superior outcomes compared to those patients treated with chemotherapy with insulin or with drugs other than metformin (OS, 20 months vs. 13.1 months vs 13.0 months, respectively, p=0.007). The remarkable activity of this agent in both preclinical and clinical lung cancer models as well as its low toxicity and tolerability in non- diabetic patients warrants further prospective studies evaluating the therapeutic efficacy with platinum based chemotherapy in NSCLC.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Carcinoma, Non-squamous Non-small-cell Lung
Metformin, Carboplatin, Pemetrexed
Moun Sinai Beth Israel Comprehensive Cancer Center
Beth Israel Medical Center
Published on BioPortfolio: 2014-10-06T18:08:21-0400
iTRAP is an open-label, multi-centre, dose escalation study of ADI PEG20 in combination with atezolizumab, pemetrexed and carboplatin in patients with advanced non-squamous non-small cell ...
A Study of Atezolizumab in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Participants Who Are Chemotherapy-Naive and Have Stage IV Non-Squamous Non-Small Cell Lung Cancer
This is a randomized, Phase III, multicenter, open-label study designed to evaluate the safety and efficacy of atezolizumab in combination with cisplatin or carboplatin + pemetrexed compar...
Multi-center, open, randomized (parallel) and comparative phase III. Eligible patients will receive bevacizumab + chemotherapy for a minimum of 4 cycles followed by bevacizumab (+ pemetre...
This is an efficacy and safety study of pembrolizumab (MK-3475) combined with platinum-pemetrexed chemotherapy versus platinum-pemetrexed chemotherapy alone in participants with advanced o...
This randomized phase II study will compare the efficacy and safety of the combination of carboplatin and pemetrexed with and without OGX-427 in patients with previously untreated advanced...
Randomized phase 2 trial of pemetrexed, pemetrexed/bevacizumab, and pemetrexed/carboplatin/bevacizumab in patients with stage IIIB/IV non-small cell lung cancer and an Eastern Cooperative Oncology Group performance status of 2.
The best treatment for patients with advanced non-small cell lung cancer (NSCLC) and a poor performance status is not well defined. In this phase 2 trial, patients were randomized to receive treatment...
Cohort G of KEYNOTE-021 (NCT02039674) evaluated the efficacy and safety of pembrolizumab plus pemetrexed-carboplatin (PC) versus PC alone as first-line therapy for advanced nonsquamous NSCLC. At the p...
There are various mechanisms underlying the resistance of EGFR-mutant lung adenocarcinoma to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We herein report a case of pulmona...
In head and neck squamous cell carcinoma (HNSCC), the occurrence of concurrent lung malignancies poses a significant diagnostic challenge because metastatic HNSCC is difficult to discern from second p...
Treatment choice for lung squamous cell carcinoma could be aided by identifying predictive biomarkers.
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).
A carcinoma derived from stratified squamous epithelium. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
A mixed adenocarcinoma and squamous cell or epidermoid carcinoma.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...