GMX1778 and its prodrug GMX1777 represent a new class of cancer drugs that targets nicotinamide phosphoribosyltransferase (NAMPT) as a new strategy to interfere with biosynthesis of the key enzymatic cofactor NAD, which is critical for a number of cell functions, including DNA repair. Using a genome-wide synthetic lethal siRNA screen, we identified the folate pathway-related genes, deoxyuridine...

Gynecologic cancers represent a significant problem worldwide. Advanced, recurrent gynecologic cancers are often refractory to chemotherapy, so new treatment regimens are needed. Pemetrexed is a third-generation, multi-targeted antifolate that has been approved for use in nonsquamous non-small cell lung cancer and malignant pleural mesothelioma in both the United States and European Union. This...

The combination of pemetrexed and sorafenib has significant clinical activity against a wide variety of tumor types in patients and the present studies were performed to determine whether sildenafil enhances the killing potential of [pemetrexed + sorafenib]. In multiple genetically diverse lung cancer cell lines, sildenafil enhanced the lethality of [pemetrexed + sorafenib]. The three-drug comb...

OBJECTIVES Findings from the largest randomized phase III trial in patients with unresectable malignant pleural mesothelioma (EMPHACIS study; n = 448) were used to examine the cost-effectiveness of pemetrexed plus cisplatin therapy versus cisplatin monotherapy in patients with the disease. The cost-effectiveness of pemetrexed/cisplatin versus alternative treatments was also examined. METHODS ...

Combination of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) with platinumcontaining standard chemotherapy failed to provide better outcomes in the first-line setting for advanced nonsmall cell lung cancer (NSCLC) in several phase III trials. The approved monotherapy of erlotinib, pemetrexed or docetaxel as the second-line regimen still remains unsatisfactory in anti-tum...

LESSONS LEARNED Difficulties in translating in vitro results into clinical practice are inevitable.Further efforts to verify the efficacy of alternative schedules of pemetrexed in solid tumors are encouraged. BACKGROUND We investigated the cytotoxic activity of pemetrexed in combination with several drugs (gemcitabine, carboplatin, vinorelbine, and mitomycin C) using different exposure schedu...

Pemetrexed is a new-generation antifolate, approved for the treatment of mesothelioma and non-small cell lung cancer, currently being evaluated for the treatment of a variety of other solid tumors. This review traces the history of antifolates that led to the development of pemetrexed and describes the unique properties of this agent that distinguish it from other antifolates. These include (a)...

INTRODUCTION Radiation recall dermatitis is a well known but still poorly understood inflammatory reaction. It can develop in previously irradiated areas and has been shown to be triggered by a variety of different drugs, including cytostatic agents. Pemetrexed may cause radiation recall dermatitis in pre-irradiated patients. CASE PRESENTATION We present the case of a 49-year-old Caucasian wo...

BACKGROUND Chemoradiotherapy is the standard treatment for locally advanced non-small cell lung cancer (NSCLC); however, it is disputed whether this treatment is suitable for patients aged ≥75. This study was conducted to determine the maximum tolerated dose (MTD) of pemetrexed for use in concurrent radiotherapy for elderly patients with locally advanced non-squamous NSCLC. METHODS The eligib...

Previous studies have suggested that astrocyte-elevated gene-1 (AEG-1) contributes to the mechanisms of resistance to various chemotherapeutics. In this study, we investigated whether AEG-1 expression level correlated with that of thymidylate synthase (TS), as higher TS expression is known to be associated with the resistance to pemetrexed chemotherapy in patients with advanced lung adenocarcin...