title: Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer.
abstract: BACKGROUND
  Patients with advanced non-small cell lung cancer (NSCLC) and impaired performance status (PS >or= 2) have limited life expectancies and decreased tolerance for drug-induced toxicities. Current treatment guidelines indicate that PS 2 patients benefit from systemic therapy. Further refinement of treatment in these patients requires reduction of treatment-associated toxicities while maintaining or improving efficacy. Paclitaxel poliglumex (PPX), a macromolecular polymer-drug conjugate of paclitaxel and poly-l-glutamic acid, may enhance the therapeutic index of paclitaxel.
  
  
  METHODS
  Chemotherapy-naive PS 2 patients with advanced NSCLC randomly received single-agent PPX (175 mg/m) or a comparator (single-agent vinorelbine or gemcitabine). The primary end point of this study was overall survival.
  
  
  RESULTS
  Overall survival was similar between treatment arms (hazard ratio [HR] = 0.95; log-rank p = 0.686). Median and 1-year survival were 7.3 months and 26%, respectively, for PPX versus 6.6 months and 26% for the control arm. There was a nonsignificant trend toward improved survival in women in the PPX arm compared with standard single agents (HR = 0.65; p = 0.069). The most frequent grade 3/4 adverse events in the treatment versus control arm were dyspnea (13% versus 17%, respectively) and fatigue (10% versus 9%). Grade 3/4 neutropenia and anemia were reduced in the PPX arm (2% versus 8% and 3% versus 9%, respectively). Neuropathy, a taxane-specific toxicity, was more common in the PPX arm; grade 3 neuropathy was limited to 3%.
  
  
  CONCLUSIONS
  Single-agent PPX, dosed at 175 mg/m, is active and well tolerated in PS 2 patients with advanced NSCLC. Patients on PPX required fewer red blood cell transfusions, hematopoietic growth factors, opioid analgesics, and clinic visits than patients receiving gemcitabine or vinorelbine.
authors.affiliation: Royal Marsden Hospital, London, United Kingdom.
authors.forename: Mary E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Popovich
authors.forename: Igor N
authors.initials: IN
authors.lastname: Bondarenko
authors.forename: Antoaneta
authors.initials: A
authors.lastname: Tomova
authors.forename: Borys T
authors.initials: BT
authors.lastname: Bilynsky
authors.forename: Yevhen S
authors.initials: YS
authors.lastname: Hotko
authors.forename: Valentin L
authors.initials: VL
authors.lastname: Ganul
authors.forename: Ippolit Y
authors.initials: IY
authors.lastname: Kostinsky
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eisenfeld
authors.forename: Larissa
authors.initials: L
authors.lastname: Sandalic
authors.forename: Fred B
authors.initials: FB
authors.lastname: Oldham
authors.forename: Bruce
authors.initials: B
authors.lastname: Bandstra
authors.forename: Alan B
authors.initials: AB
authors.lastname: Sandler
authors.forename: Jack W
authors.initials: JW
authors.lastname: Singer
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; D011099:Polyglutamic Acid; D017239:Paclitaxel; C509139:paclitaxel poliglumex; D000093542:Gemcitabine