Lung cancer : journal of the International Association for the Study of Lung Cancer
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Lung cancer is the most common cause of cancer-related deaths worldwide, and the discovery and implementation of more effective therapy remains challenging. The development of agents that target the epidermal growth factor receptor/human epidermal growth factor receptor 1 (EGFR/HER1) signal transduction pathway have provided a class of novel targeted therapies that are applicable in the treatment of non-small-call lung cancer (NSCLC). Current challenges include the determination of how best these promising new agents can be integrated into current methods of treatment for patients with NSCLC, and clarification of the extent to which early lines of treatment can influence outcome in the later stages.
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The inhibition of topoisomerase I by topotecan results in a compensatory increase in topoisomerase II associated with increased in vitro sensitivity of tumors to etoposide. Maximal synergy has been observed for the sequence of topotecan followed by etoposide. Carboplatin has clinical activity when combined with either of these two agents. ⋯ The fourth patient on dose level 3 achieved a partial response, but had to be removed from protocol therapy after cycle 5 because of recurrent grade 4 thrombocytopenia. In conclusion, neutropenia and thrombocytopenia were dose-limiting. The maximum tolerated dose (MTD) is topotecan 3mg/day p.o. days 1-5, carboplatin AUC 5i.v. day 6, and etoposide 150 mg/day p.o. days 6-10 with filgrastim.