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.
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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.
