Rational drug sequencing of paclitaxel, gemcitabine and carboplatin in patients with untreated stage IV and select stage IIIB non-small cell lung cancer.

INTRODUCTION: To conduct a phase II study evaluating the efficacy of rationally sequenced paclitaxel, gemcitabine, and carboplatin in patients with stage IV or select stage IIIB non-small cell lung cancer (NSCLC). METHODS: Patients with select stages IIIB (pleural effusion) and IV NSCLC with an ECOG performance status of 0-1 and no prior chemotherapy for their disease were eligible to participate. Treatment was delivered as follows: paclitaxel at 70 mg/m2 followed by gemcitabine at 300 mg/m2 on day 1, with carboplatin (AUC 5) on day 2 of a 28-day cycle. Response was assessed after every two cycles of therapy. The primary endpoint of this trial was response rate, with secondary endpoints of time to progression and 1 year overall survival. RESULTS: Twenty patients were enrolled on protocol, one of whom never received chemotherapy. The median number of cycles delivered was 3 (range 0-8). A partial response rate of 42% (8/19; 95% CI: 20-67%) and a stable disease rate of 11% (2/19; 95% CI: 1-33%) were observed. The median overall survival time was 9.6 months (95% CI: 4.6-16.6), with a 1 year overall survival rate of 42.1% (95% CI: 24.9-71.3%). Eight patients (42%) stopped treatment due to toxicity. CONCLUSION: Paclitaxel followed by gemcitabine and then carboplatin is an active, albeit complex, regimen in the treatment of patients with advanced NSCLC with insufficient advantage to justify continuation of this regimen.

A phase II trial of imatinib mesylate in patients with metastatic pancreatic cancer.

OBJECTIVES: The aim of the study was to assess the clinical efficacy and toxicity of single-agent imatinib mesylate in patients with advanced, unresectable metastatic pancreatic cancer. METHODS: Previously treated or untreated patients with histologically proven, unresectable pancreatic adenocarcinoma with adequate organ and bone marrow function were enrolled. Patients received imatinib 400 mg orally twice a day for a 28-day cycle. Response was evaluated every 4 weeks by imaging scans. Response was defined as lack of tumor progression at 3 months. RESULTS: Eleven patients were enrolled, and 9 were evaluable for response. Best response was stable disease in 3 patients after 2 cycles of therapy. All of them subsequently progressed. No patients remained on treatment for 3 months or longer, which was the response end point. Median time to tumor progression was 47 days (range, 19-76 days) and median overall survival was 118 days (range, 40-221 days). The first 3 patients received imatinib 400 mg orally twice a day. Due to unexpected grades 2 and 3 toxicities, the dose was reduced to 600 mg daily which was well tolerated. Most common adverse events included grades 1 to 2 edema, liver enzyme elevations, nausea, and rash. CONCLUSION: Single-agent imatinib does not have a significant activity in pancreatic cancer.