Search

The efficacy and toxicity of combined paclitaxel (PTX) and gemcitabine (GEM) was evaluated as a protocol for first-line chemotherapy in 40 patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel, 100 mg/m2, was administered intravenously (IV) as a 1-h infusion, followed by GEM, 1,000 mg/m2, IV over 30 min on days 1 and 8 of a 21-day cycle. The median age of patients was 66 years with a range of 33–75 years. Nearly all patients (39/40) had an ECOG performance status of 0 or 1. Thirteen patients (32%) had initial stage IIIB disease and 27 patients (68%) had stage IV disease. Histological subtypes were adenocarcinoma (73%) and squamous cell carcinoma (25%). Twenty-two patients (55%) achieved a partial response and none achieved a complete response, giving an overall response rate of 55% (95% confidence interval: 38.2–71.8%). Disease stability was achieved in 14 patients (35%), and 4 patients (10%) had progressive disease. The median survival time was 11.9 months (95% CI: 10.3–14 months), with a 1-year survival rate of 47.5%. Grade 3 or 4 hematological toxicities observed included neutropenia in 37.5%, anemia in 2.5%, and thrombocytopenia in 5.0% of these patients. Non-hematologic toxicities were mild, with the exception of grade 3 and 4 pneumonitis. There were no deaths due to toxicity. Weekly chemotherapy with PTX plus GEM is effective and is acceptable for the first line treatment of advanced NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: RPI.4610 (ANGIOZYME) is a chemically stabilized ribozyme targeting vascular endothelial growth factor receptor 1. The purpose of this study was to evaluate the safety and pharmacokinetics of RPI.4610 in combination with carboplatin and paclitaxel in patients with advanced solid tumors. Methods: The study used a sequential treatment design evaluating a single dose level for all three drugs: paclitaxel 175 mg m-² and carboplatin AUC=6 on day 1 of a 21-day cycle, and RPI.4610 100 mg m-² day-± beginning on day 8 and continuing daily thereafter. Pharmacokinetic samples were drawn on day 1 of courses 1 (chemotherapy alone) and 2 (chemotherapy+RPI.4610), and on day 8 of course 1 (RPI.4610 alone). Ratios were generated by comparing the pharmacokinetic parameters for the combination of carboplatin with paclitaxel when administered alone or together with RPI.4610. Results: Twelve patients were enrolled in this trial and received two to six courses of treatment each. The most common grade 3–4 toxicities were neutropenia (three patients), thrombocytopenia (three patients), pain (three patients), anemia (two patients) and fatigue (two patients). The ratio of the mean maximum plasma concentration (Cmax) for carboplatin when administered with paclitaxel alone versus when administered with paclitaxel and RPI.4610 was 1.07 (90% confidence interval, 0.77–1.37). Similarly, the ratio of the mean AUC0-last for carboplatin was 1.04 (0.73-1.35). For paclitaxel the ratio of the mean Cmax when administered with carboplatin alone versus with carboplatin and RPI.4610 was 1.17 (1.03–1.31), and the ratio of the mean AUC0-last was 1.17 (1.04–1.30). Objective tumor responses were observed and included one patient with a complete response (bladder cancer) and one patient with a partial response (esophageal cancer). Conclusions: These results indicate that RPI.4610, carboplatin, and paclitaxel can be administered safely in combination without substantial pharmacokinetic interactions. [ABSTRACT FROM AUTHOR]