Weekly, high-dose paclitaxel in advanced lung carcinoma: a phase II study with pharmacokinetics by the Cancer and Leukemia Group B.

BACKGROUND: The Cancer and Leukemia Group B conducted a Phase II trial to evaluate the efficacy, toxicity, and pharmacokinetics of paclitaxel administered at a maximum dose density for patients with chemotherapy-naïve, advanced-stage non-small cell lung carcinoma (NSCLC). METHODS: Patients with Stage IIIB/IV or recurrent NSCLC, a performance status (PS) score of 0-1, and no history of chemotherapy exposure were eligible. Paclitaxel, 150 mg/m(2), was administered over 3 hours during Weeks 1-6 of an 8-week cycle. Doses were modified for ANC < 1500/microL or for >or= Grade 2 neuropathy on the day of therapy. Treatment continued until toxicity or disease progression. Pharmacokinetics were assessed at Weeks 1, 3, and 5 of Cycle 1. RESULTS: Thirty-eight patients (median age, 64 years; range, 31-81 years) were treated. There were 21 males (PS = 0 for 17). Eleven patients had received previous radiation, 2 had brain metastases, 25 had adenocarcinoma, 23 had Stage IV disease, 6 had StageIIIB disease, and 9 had recurrent disease. Grade 3-4 granulocytopenia occurred in 39% of patients. There were no deaths due to toxicity. Grade 2 or 3 neuropathy occurred in 29% and 24% of patients, respectively. Ten (27%) patients had Grade 3 hyperglycemia (glucose concentration > 250 mg/dL). There were 16 partial responses (42%; 95% confidence interval [CI], 26-59%). The median survival period was 12.3 months (95% CI, 7.9-19.6%), and the 1-year and 2-year survival rates were 52% (95% CI, 39-71%) and 26% (95% CI, 15-45%), respectively. Paclitaxel pharmacokinetics were consistent with published values and clearance was not induced. Older age and hyperglycemia were associated with greater neurotoxicity. CONCLUSIONS: Paclitaxel at 150 mg/m(2) per week x 6 every 8 weeks can be administered safely in the cooperative group setting. These Phase II data are comparable to those associated with combination therapy. The weekly dose-dense schedule may be more active than conventional schedules.

Duke Scholars

Author James Emmett Herndon II Biostatistics & Bioinformatics, Division of Biostatistics