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.
OBJECTIVE
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).


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%.


CONCLUSIONS
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.
Rizvi
Naiyer A
NA
Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. rizvin@mskcc.org
Riely
Gregory J
GJ
Azzoli
Christopher G
CG
Miller
Vincent A
VA
Ng
Kenneth K
KK
Fiore
John
J
Chia
Gloria
G
Brower
Martin
M
Heelan
Robert
R
Hawkins
Michael J
MJ
Kris
Mark G
MG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D000740:Anemia / Q000139:chemically induced; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D015996:Survival Rate
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D017239:Paclitaxel