A phase II trial of weekly paclitaxel and gemctiabine infused at a constant rate in patients with advanced non-small cell lung cancer.

Background: Gemcitabine and paclitaxel both have significant single agent activity in non-small cell lung cancer (NSCLC). Because both are cell cycle and phase specific in their mechanism of action, frequent exposure should optimize activity. Phase I data support that gemcitabine is maximally converted to the active metabolite when it is infused at a rate of 10 mg/(m2 min). Based on this, we designed a phase II trial to examine gemcitabine 800 mg/m2 infused over 80 min with paclitaxel 110 mg/m2 infused over 3 h both on days 1, 8 and 15 every 28 days as first line therapy in patients with advanced NSCLC. The primary objectives were to assess the response rate, toxicity and survival of the combination in advanced NSCLC. Secondary objectives were to determine the effect of paclitaxel on the pharmacokinetic (PK) distribution of gemcitabine, the ability to achieve a concentration of 10-20 microM when gemcitabine was infused at a rate of 10 mg/(m2 min), as well as to assess the quality of life (QOL) with the functional assessment of cancer therapy-lung (FACT-L) questionnaire.

Methods: Patients with NSCLC, no prior treatment, ECOG performance status (PS) 0-1, adequate bone marrow, renal, and hepatic function were eligible for this trial. Paclitaxel 110 mg/m2 was infused over 3 h, followed by gemcitabine 800 mg/m2 infused over 80 min on days 1, 8, and 15 every 28 days for the first 2 patients, and then amended to days 1 and 8 every 21 days after the first 2 patients required day 15 dose omissions due to myelosupression.

Results: Thirty-nine patients were treated. Nine PS = 0; 28 PS = 1; Stage IIIB = 3, Stage IV = 36; median age 62 (range: 39-77). A median of six cycles (range: 0-10) was delivered. Grade 3-4 toxicities observed in > or =10% of patients included leucopenia in 26%, neutropenia in 28%, dyspnea in 13%, febrile neutropenia in 3% (1 patient). Fourteen of 39 (35%, 95% CI: 21-53%) patients had a partial response (PR), 14 of 39 (35%, 95% CI: 21-53%) had stable disease (SD) and 5 patients (13%, 95% CI: 4-27%) had progressive (PD). Median survival was 10.4 months (95% CI: 5.3-13.6). One-and two-year survival rates were 35% (95% CI: 21-53%) and 5% (95% CI: 0.6-17%), respectively. QOL as measured by the FACT-L and the trial outcome index (TOI) did not change significantly from baseline over the course of therapy.

Conclusions: Paclitaxel and gemcitabine is an active and well-tolerated combination in advanced NSCLC. Patients on this trial had no significant change in their QOL as assessed by the FACT-L questionnaire.