title: Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor patients with emphasis on non-small cell lung cancer.
abstract: BACKGROUND
  Despite advances in targeted therapies, there is an ongoing need to develop new and effective cytotoxic drug combinations in non-small cell lung cancer (NSCLC). Based on preclinical demonstration of additive cytotoxicity, we evaluated the safety and efficacy of combining pemetrexed and nanoparticle albumin bound (nab) paclitaxel with a focus on NSCLC for phase II expansion.
  
  
  METHODS
  A 3 + 3 dose-escalation design was used to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels were tested: pemetrexed 500 mg/m(2) day 1 and nab-paclitaxel day 1 at 180, 220, & 260 mg/m(2) every 21 days. Phase II eligibility included advanced NSCLC, ≤2 line prior therapy, PS 0-1, adequate organ function. Primary endpoint for further study was response rate (RR) ≥ 25%.
  
  
  RESULTS
  Planned dose escalation was completed without reaching the MTD. The RP2D was pemetrexed 500 mg/m(2) and nab-paclitaxel 260 mg/m(2). The phase II portion accrued 37 pts before early closure due to increasing first-line pemetrexed/platinum doublet use in non-squamous NSCLC. In 31 assessable phase II patients there were 5 partial responses, 12 stable disease, 14 progressive disease. The median overall survival was 8.8 months; progressive disease 4.4 months and disease control 15.6 months.
  
  
  CONCLUSIONS
  Pemetrexed 500 mg/m(2) day 1 with nab-paclitaxel 260 mg/m(2) was feasible and well tolerated. The phase II component demonstrated activity in second/third-line therapy of advanced NSCLC; response rate 14% and disease control rate 46%. Treatment practice patterns of advanced NSCLC have evolved; further trials of this regimen are not planned.
authors.affiliation: British Columbia Cancer Agency, 600 W 10th Avenue, Vancouver, BC, V5Z 4E6, Canada, cho@bccancer.bc.ca.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Ho
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: Randeep S
authors.initials: RS
authors.lastname: Sangha
authors.forename: Derick
authors.initials: D
authors.lastname: Lau
authors.forename: Primo
authors.initials: P
authors.lastname: Lara
authors.forename: Helen K
authors.initials: HK
authors.lastname: Chew
authors.forename: Laurel
authors.initials: L
authors.lastname: Beckett
authors.forename: Philip C
authors.initials: PC
authors.lastname: Mack
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Riess
authors.forename: David R
authors.initials: DR
authors.lastname: Gandara
mesh_terms: D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D000068437:Pemetrexed
chemical_list: C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D017239:Paclitaxel