Dilemmas in Management: The Controversial Role of Chemotherapy in PS 2 Advanced NSCLC and the Potential Role of CT-2103 (Xyotax™)

Abstract

Platinum-based chemotherapy improves long-term survival in patients with advanced non-small cell lung cancer (NSCLC). Meta-analyses have demonstrated an improvement in median and 1-year survival times as well as quality of life. However, these benefits are largely confined to patients with a good performance status (PS), one of the most critical determinants influencing outcome. Several clinical trials that initially included PS 2 patients ultimately discontinued their enrollment due to a high propensity of adverse reactions to treatment. The advent of more active, less toxic agents has revitalized investigator interest in treating PS 2 patients. CT-2103 is a novel paclitaxel conjugate undergoing investigation in the treatment of advanced NSCLC. The median survival for PS 2 patients treated with single-agent CT-2103 in one small trial proved similar to that reported for paclitaxel/carboplatin in NSCLC patients and was associated with an improved safety profile compared with conventional taxanes. Phase III studies comparing CT-2103 as a single agent and in combination with carboplatin to current standards of care are in progress. Unlike a well-defined population with good PS, the therapeutic index in PS 2 patients is narrower and not as clearly defined. These and other efforts will determine the optimal mode of therapy in PS 2 individuals with NSCLC.