Second- and third-line treatments in non-small cell lung cancer

Abstract

Slow but steady progress has been made in the treatment of advanced non-small cell lung cancer. For first-line therapy, multiple chemotherapy combination therapies can extend survival and improve quality of life. And recently, for the first time ever, a noncytotoxic agent, the antivascular endothelial growth factor antibody bevacizumab, has been shown to improve survival when added to chemotherapy. Striking improvements have also been made in second-line treatment. In August 2004, only one agent was US Food and Drug Administration (FDA) approved in this setting, docetaxel, but by the beginning of 2005, two more were available, pemetrexed and erlotinib. All three of these drugs can significantly benefit patients, with 1-year survival in excess of 30%. Choosing between the three agents can be challenging, and this review focuses on the toxicity differences and predictors of response that can help guide this decision. Docetaxel and pemetrexed, both traditional intravenous cytotoxins, are excellent options for patients who have shown some response to first-line chemotherapy, but at this time, no other means exist to determine likelihood of response. When choosing between the two, pemetrexed causes significantly less neutropenia than does docetaxel, at least on the standard every-3-week regimen. With erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, there are factors that can predict for response, including little or no smoking history, and adenocarcinoma histology. Therefore, patients who fit these characteristics are good candidates for second-line erlotinib. However, the relationship between response to erlotinib and improved survival remains unclear, and several laboratory analyses that may help further, such as evaluation of EGFR gene copy number, are still under development. Although erlotinib is the only FDA-approved option currently available for third-line therapy, many patients with good performance status may benefit from third-line therapy and beyond. In addition to the approved second-line options, other single-agent chemotherapies to consider for treatment beyond second-line are gemcitabine, irinotecan, and oral topotecan. Many new drugs, including bevacizumab, ZD6474 (AstraZeneca, Wilmington, DE), sorafenib, cetuximab, paclitaxel poliglumex, epothilones, and others, alone or in combination with traditional agents, are currently undergoing investigation and hold great promise.

Clinical predictive factors for advanced non-small cell lung cancer (NSCLC) patients receiving third-line therapy: Selecting the unselectable?

“…According to published data, docetaxel, pemetrexed and the epidermal growth receptor (EGFR) tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib are all acceptable choices for third-line therapy [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Unfortunately, the clinical benefit deriving from third-line treatments is often limited to a small proportion of the patients treated, whereas it is not uncommon to observe toxic sideeffects with lack of efficacy.…”

Engineering of self-assembled nanoparticle platform for precisely controlled combination drug therapy

“…Using cisplatin (27)(28)(29) and Dtxl (30)(31)(32)(33)(34)(35), two widely used Food and Drug Administrationapproved chemotherapeutics with different solubility profiles, and prostate cancer as a model disease, we demonstrate targeted drug delivery to PSMA-expressing cells. First, a functionalizedpoly(lactic acid) (PLA) polymer was synthesized and derivatized with platinum(IV) [Pt(IV)] prodrug pendants which, after reduction, release cisplatin.…”

Pemetrexed in Third and Fourth Line Chemotherapy for Non Squamous Non Small-Cell Lung Cancer

“…The authors quated like candidates for third-line chemotherapy: single-agent gemcitabine, irinotecan, and oral topotecan [8]. The study published by Song et al was a retrospective study which confirmed the small but proved benefit of third-line chemotherapy.treated with doublet of cytostatics, 2.80 months for single-agent and 2.97 months for EGFR-TKIs arms (P=0.033) [9].…”