Phase I/II trial of weekly intravenous 130-nm albumin-bound paclitaxel as initial chemotherapy in patients with stage IV non-small-cell lung cancer.

Abstract

PURPOSE:

Nanoparticle albumin-bound paclitaxel (NAB-paclitaxel) is an albumin-bound formulation of paclitaxel that has demonstrated improved efficacy compared with paclitaxel in the treatment of metastatic breast cancer. We undertook this trial to determine the maximum-tolerated dose (MTD) and single-agent activity of NAB-paclitaxel administered on a weekly basis to patients with stage IV non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS:

This was an open-label, single-arm, phase I/II study. Patients were treated with NAB-paclitaxel intravenously during 30 minutes without corticosteroid or antihistamine premedications on days 1, 8, and 15 of a 28-day cycle. Radiologic tumor assessment was performed every 8 weeks.

RESULTS:

Dose levels of 100 and 125 mg/m(2) were tolerated without dose-limiting toxicities (DLTs). At 150 mg/m(2) the MTD was exceeded; two of three patients experienced a DLT (grade 3 sensory neuropathy and febrile neutropenia). The 125 mg/m(2) dose level was expanded and determined to be the MTD. A total of 40 patients were treated at 125 mg/m(2). The objective response rate was 30% (12 of 40 patients; 95% CI, 16% to 44%), median time to progression was 5 months (95% CI, 3 to 8 months), and median overall survival was 11 months (95% CI, 7 months to not reached). The 1-year survival was 41%.

CONCLUSION:

NAB-paclitaxel 125 mg/m(2) administered on days 1, 8, and 15 of a 28-day cycle was well tolerated and demonstrated encouraging single-agent activity. No corticosteroid premedication was administered and no hypersensitivity reactions were seen. Additional studies of single-agent NAB-paclitaxel as well as platinum-based combinations are warranted.

• Authors: Naiyer A Rizvi, Gregory J Riely, Christopher G Azzoli, Vincent A Miller, Kenneth K Ng, John Fiore, Gloria Chia, Martin Brower, Robert Heelan, Michael J Hawkins, Mark G Kris
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 26 Issue 4 Pg. 639-43 (Feb 01 2008) ISSN: 1527-7755 [Electronic] United States
• PMID: 18235124 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Albumins (administration & dosage, adverse effects, pharmacokinetics)
• Anemia (chemically induced)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality, pathology)
• Diarrhea (chemically induced)
• Drug Administration Schedule
• Female
• Humans
• Infusions, Intravenous
• Lung Neoplasms (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Neutropenia (chemically induced)
• Paclitaxel (administration & dosage, adverse effects, pharmacokinetics)
• Peripheral Nervous System Diseases (chemically induced)
• Survival Rate