Vincent A. Miller, MD

Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR), such as erlotinib (Tarceva) and gefitinib (Iressa), have shown remarkable activity in a portion of patients with non–small-cell lung cancer (NSCLC).

The comprehensive review by Dr. Karen Kelly meticulously outlines the rationale for the study of irinotecan in non-small-cell lung cancer (NSCLC), summarizes results of trials of this agent as monotherapy and as a component of doublet and triplet regimens in previously untreated NSCLC patients, and then reviews its role in previously treated NSCLC patients.

Currently there are a number of available agents that are moderately active in non–small-cell lung cancer (NSCLC). These include cisplatin (Platinol), gemcitabine (Gemzar), vinorelbine (Navelbine), paclitaxel (Taxol), docetaxel (Taxotere), and irinotecan (Camptosar). How best to combine them, maximizing survival while minimizing toxicity, is the subject of intense investigation.

The Southwest Oncology Cooperative Group (SWOG) conducted a study in which single-agent docetaxel (Taxotere) was used as “consolidation” therapy following concurrent chemoradiotherapy (abstract #1916). A previous SWOG study (S90-19) (Proc Am Soc Clin Oncol 16: 446a [abstract 1600], 1997) established that chemotherapy with cisplatin (Platinol)/etoposide could be given concurrently with definitive thoracic irradiation both safely and effectively. In this earlier trial, following the completion of irradiation, two additional cycles of cisplatin/etoposide were given.

In medically suitable patients with stage III (locally advanced) non–small-cell lung cancer, the use of cisplatin (Platinol)-based chemotherapy as induction therapy prior to definitive local therapy has been shown to improve survival (J Natl Cancer Inst 86:673-680, 1994; Ann Intern Med 125:723-729, 1996). This is true regardless of whether the local treatment modality used is surgery or thoracic irradiation. However, because cisplatin therapy is particularly toxic, there is interest in studying other agents in the induction setting. Given its activity in non–small-cell lung cancer, docetaxel (Taxotere) is one logical agent to investigate.

A meta-analysis of randomized controlled trials (Br Med J 311:899-909, 1995) has shown that the use of cisplatin (Platinol)-based combination chemotherapy in patients with good performance status leads to a modest improvement in median survival and an absolute increase in 1-year survival proportion of 10%. There are several different platinum-based regimens approved by the Food and Drug Administration for use in advanced non–small-cell lung cancer. Whether any one regimen is superior is unclear. A recent randomized controlled trial found no difference in median survival and quality of life between carboplatin (Paraplatin)/paclitaxel (Taxol)-the most commonly used regimen in the United States-and cisplatin/vinorelbine (Navelbine)-a regimen more popular in Europe and Canada (Proc Am Soc Clin Oncol 18: 461a [abstract 1777], 1999). The newer agents gemcitabine (Gemzar) and docetaxel (Taxotere) are among the most active single agents in non–small-cell lung cancer, and use of either in combination with cisplatin has shown promise.

These abstracts examine the use of single-agent docetaxel (Taxotere), an antimicrotubule agent and one of the most active drugs against NSCLC currently available, in the first- and second-line settings.