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
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/m2/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/m2/wk, the maximum tolerated dose, was initiated;
data are available for the first 25 patients. Eighty-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/μL/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%,
Conclusion: Paclitaxel administered on a
weekly schedule allows enhanced dose intensity, has a protective or
stimulatory effect on platelets, and is active in NSCLC.