Inhibition of thymidylate synthase (TS) results in a transient "flare" in DNA thymidine salvage pathway activity measurable with FLT ([18F]thymidine)-positron emission tomography (PET). Here we characterize this imaging strategy for potential clinical translation in non-small cell lung cancer (NSCLC). Since pemetrexed acts by inhibiting TS, we defined the kinetics of increases in thymidine salv...

Reactive oxygen species (ROS) can promote or inhibit tumorigenesis. In mesothelioma, asbestos exposure to serous membranes induces ROS through iron content and chronic inflammation, and ROS promote cell survival signaling in mesothelioma. Moreover, a current chemotherapy regimen for mesothelioma consisting of a platinum and antifolate agent combination also induce ROS. Mesothelioma is notorious...

PURPOSE Present chemotherapeutic regimens are marginally efficient in tumor cells being particularly resistant to radiotherapy and/or chemotherapy. We hypothesized that unresponsiveness of tumors to conventional therapeutic agents might be due to inappropriate gene expression resulting from epigenetic modifications and leading to transcriptional silencing. The goal of this study was to evaluate...

Malignant pleural mesothelioma (MPM) is a disease with a poor prognosis, related in part to the aggressiveness of this disease, and in part due to the lack of drugs that have demonstrated tumor activity. Historically, antifolates such as methotrexate have been the most active drugs in the treatment of mesothelioma. Newer antifolates have recently demonstrated higher efficacy than older regimens...

BACKGROUND Previous studies of the gemcitabine-pemetrexed combination in patients with late-stage non-small-cell lung cancer (NSCLC) utilized a 90-min delay between gemcitabine and pemetrexed administration. This phase II study evaluated activity when these agents were administered in rapid succession. MATERIALS AND METHODS Chemonaive patients with late-stage NSCLC received gemcitabine 1250 m...

BACKGROUND The current standard first-line chemotherapy for malignant pleural mesothelioma (MPM) is pemetrexed and cisplatin. However, other regimens, with or without a platinum agent, are reported to be effective in the treatment of MPM. PATIENTS AND METHODS Patients who were diagnosed with MPM and treated with chemotherapy between January 1999 and June 2010 at the Osaka Prefectural Medical ...

The present study evaluated the efficacy and safety of pemetrexed, carboplatin and bevacizumab, followed by maintenance pemetrexed and bevacizumab, in chemotherapy-naïve patients with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). The patients were administered pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve, 6.0 mg/ml × min) and bevacizumab (15 mg/k...

Pemetrexed (Alimta) is a novel antimetabolite that inhibits the folate-dependent enzymes thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. Pemetrexed has demonstrated activity in clinical trials in a variety of tumor types, including lung, breast, colon, mesothelioma, pancreatic, gastric, bladder, head and neck, and cervix. Pemetrexed is rapidly me...

BACKGROUND Eli Lilly and the China Primary Health Care Foundation are currently implementing a patient assistance program (PAP) in China, which allows first-line nonsquamous non-small-cell lung cancer (NSCLC) patients who complete four cycles of pemetrexed induction therapy to receive free, continuous pemetrexed maintenance therapy. OBJECTIVE To estimate the cost-effectiveness of pemetrexed m...

Chemotherapy with pemetrexed plus carboplatin followed by pemetrexed maintenance therapy is a first-line regimen for patients with advanced non-squamous non-small-cell lung cancer. This phase II clinical study investigated the efficacy and safety of this regimen in older patients (aged ≥65 years) with advanced non-squamous non-small-cell lung cancer. All patients received 4 courses of induction...