Our group previously described the activity of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (given as a 24-hour infusion) in 51 patients with advanced non-small cell lung cancer. To facilitate outpatient administration, the regimen was modified to infuse paclitaxel over 1 hour. Between February 1995 and August 1996, 63 patients with advanced non-small cell lung cancer were accrued by the Vanderbilt Cancer Center and its affiliate network. The first four patients received paclitaxel 175 mg/m2; all subsequent patients received paclitaxel 200 mg/m2. The carboplatin dose was determined using the Calvert formula, with a target area under the concentration-time curve of 6. Cycles were repeated every 4 weeks, to a maximum of six cycles. The median age of the patients was 62 years. There were 43 men and 20 women. Ten patients were stage IIIB and 53 were stage IV. Patients with Eastern Cooperative Oncology Group performance status < or =2 were enrolled. There were three complete remissions and 13 partial remissions, for an overall response rate of 25%. Median survival was 32 weeks. This compares with a response rate of 27% and a median survival of 38 weeks observed in our previous study, using 24-hour paclitaxel plus the same dose of carboplatin. Grade 3/4 leukopenia occurred in 47% versus 3% of treatment cycles in the 24-hour versus 1-hour patient groups, respectively. Febrile neutropenia was similar and occurred in 7% versus 4% of treatment cycles. Grade 1 to 3 neurotoxicity occurred in 7% versus 41% of patients in the 24-hour versus 1-hour schedule groups, respectively. Likewise, the incidence of grade 1 to 3 arthralgia/myalgia was greater among patients receiving 1-hour infusion of paclitaxel (3.5% v 28%). Although not randomized, these data suggest that survival may be comparable whether paclitaxel is given by short or prolonged infusion in advanced non-small cell lung cancer. Toxicity profiles differ, however, with greater myelosuppression following 24-hour paclitaxel, but a higher incidence of neurotoxicity and arthralgia/myalgia with the 1-hour infusion.