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

✍ Scribed by Wallace Akerley; James E. Herndon; Merrill J. Egorin; Alan P. Lyss; Hedy L. Kindler; Dianne M. Savarese; Carol A. Sherman; D. Marc Rosen; Donna Hollis; Mark J. Ratain; Mark R. Green

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 92 KB
• Volume: 97
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.11375

✦ Synopsis

Abstract

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/μL or for ≥ 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 × 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. Cancer 2003;10:2480–6. © 2003 American Cancer Society.

DOI 10.1002/cncr.11375