Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Response to radiotherapy in brain metastases and survival of patients with non-small cell lung cancer.

The present study involves non-small cell lung (NSCLC) cancer patients with brain metastases, who were treated with radiation therapy, and our aim was to determine response rate and survival. A total of 167 patients were recruited, 155 (125 male, 30 female) of whom were evaluable. Performance status was 0-2 and histology or cytology included 66 (42.58%) adenocarcinomas, 62 (40.00%) undifferentiated and 27 (17.42%) squamous cell carcinomas. The stage of disease at diagnosis was IIIA-B in 92 (59.35%) patients and IV in 63 (40.65%). All patients had whole brain irradiation (3 Gy x 5 days/week for 2 weeks to a total dose of 30 Gy), which was performed by a linear accelerator and a 6-MV photon beam. Objective response was observed in 59/155 (38.06%) patients with 17 (10.97%) complete and 42 (27.09%) partial responses, and median survival of 5 months for all patients [95% confidence interval (CI) 3.9-6.1]. Responders had statistically significant longer survival than non-responders. Although responders represented less than half of our patients with NSCLC and brain metastases, they had significantly longer survival.