Preliminary results of combined therapy with topotecan and carboplatin in advanced non-small-cell lung cancer

Topotecan is a topoisomerase I inhibitor and an analogue of camptothecin wi th demonstrated activity in small-cell lung cancer. However, less is known about the potential role of topotecan in advanced non-small-cell lung cance r (NSCLC). Platinum-based combination therapy is currently recommended in N SCLC patients presenting with good performance status. Because topotecan de monstrates a novel mechanism of action, its investigation in platinum combi nations is warranted. In phase I/II trials of topotecan given as part of a cisplatin-based regimen, significant antitumor activity has been observed, providing the rationale for conducting further studies aimed at assessing s urvival benefit. However, this combination exhibits sequence dependence, wi th increasing hematologic toxicity observed when cisplatin is administered on day 1 of a 5-day topotecan course. Cisplatin has been associated with do se-limiting non-hematologic toxicities. Carboplatin exhibits a different to xicity profile compared with cisplatin, which makes it an attractive agent to study in combination. A hypothesis can be made that carboplatin in combi nation with newer agents such as topotecan might compare favorably with cla ssic cisplatin-based regimens, particularly with respect to efficacy:toxici ty ratio. Therefore, a phase II study was initiated to determine the effica cy, toxicity, and safety of carboplatin-topotecan combination in advanced N SCLC. Preliminary results reported here show that topotecan with carboplati n is generally well tolerated with manageable hematologic toxicity. Indirec t comparison with cisplatin-topotecan combination suggests a lower incidenc e of dose-limiting nonhematologic toxicity. Whether or not the carboplatin- topotecan regimen is able to offer tumor response and survival benefit comp arable to those observed with cisplatin-based combinations remains to be es tablished. Copyright (C) 2001 S. Karger AG, Basel.