Topotecan in the treatment of non-small cell lung cancer

According to the American Cancer Society, 178,100 new cases of lung cancer were predicted in 1997, with an estimated 5-year relative survival rate of 11% to 14%. Non-small cell lung cancer (NSCLC), the most prevalent type of lung cancer, presents an extraordinary challenge to the oncologist, because most patients present with advanced unresectable disease. Cisplatin, one of the most effective single agents against NSCLC, has only moderate antitumor effect and limited impact on survival. Combination regimens also show little increase in survival. In the search for better treatments for NSCLC, new agents with novel mechanisms of action have been explored. In preclinical studies, topotecan (Hycamtin; SmithKline Beecham Pharmaceuticals, Philadelphia, PA), a topoisomerase I inhibitor, demonstrated activity in a variety of animal tumor models. Results from subsequent phase I and phase II clinical trials, summarized here, suggest that topotecan has modest activity against NSCLC and that its role in the treatment of this disease should be evaluated further.