Paclitaxel in advanced non-small cell lung cancer - An alternative high-dose weekly schedule

Study objectives: Sequential phase I and phase II trials of paclitaxel using an extended weekly schedule were performed to explore its effect on tolerance, limits of dose intensity, and activity at maximum dose intensity in disseminated non-small cell lung cancer (NSCLC). Design: Patients with stage IIIB/IV NSCLC were eligible if they had a performance status of 0 to 2, no previous chemotherapy, and normal organ function. Paclitaxel was administered as a 3-h infusion weekly for 6 weeks of an 8-week cycle. Doses were modified for toxicity observed on the day of treatment. Measurements and results: Paclitaxel, 100 to 200 mg/m(2)/wk, was administered in the phase I trial. Dose escalation was limited primarily by neutropenia, and a relationship between dose and response was noted. A phase II trial of paclitaxel, 175 mg/m(2)/wk, the maximum tolerated dose, was initiated; data are available for the first 25 patients. Eighy-three, 75, 58, and 50% of intended doses were delivered during cycles one to four, respectively. Grade 2 or 3 neuropathy occurred in nine patients, but improved in all following dose reduction. Platelet counts rose by 17,000/mu L/wk. Partial responses occurred in 14 of 25 patients (56%; confidence interval, 46 to 66%), The duration of response was 6 months, and 1- and 2-year survival rates were 53% and 18%, respectively. Conclusion: Paclitaxel administered on a weekly schedule allows enhanced dose intensity, has a protective or stimulatory effect on platelets, and is active in NSCLC.