title: 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: 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.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. rizvin@mskcc.org
authors.forename: Naiyer A
authors.initials: NA
authors.lastname: Rizvi
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riely
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Azzoli
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Ng
authors.forename: John
authors.initials: J
authors.lastname: Fiore
authors.forename: Gloria
authors.initials: G
authors.lastname: Chia
authors.forename: Martin
authors.initials: M
authors.lastname: Brower
authors.forename: Robert
authors.initials: R
authors.lastname: Heelan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hawkins
authors.forename: Mark G
authors.initials: MG
authors.lastname: Kris
mesh_terms: 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
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D017239:Paclitaxel