Emerging role of topotecan in first-line therapy of XXXX .

@entity1 @entity137 @entity882 @entity5 @entity1398 @entity151
Topotecan, a novel topoisomerase I inhibitor, is an established treatment for @entity1 with recurrent @entity151 ( @entity151 ), with antitumor response rates of approximately 20% and median survival of approximately 32 weeks in @entity1 with @entity5 . Topotecan's comparable activity relative to other agents used in @entity151 and its novel mechanism of action, noncumulative @entity137 , and in vitro synergy with other active agents have provided the rationale for investigating topotecan in first-line therapy. Furthermore, topotecan penetrates the blood-brain barrier and is potentially useful for the relatively large subset of @entity1 with @entity151 and brain metastases. In early studies of topotecan in brain metastases, encouraging antitumor activity has been observed. In several feasibility and phase II studies of topotecan as single-agent therapy in @entity1 with extensive- and limited-stage @entity5 and as part of novel first-line combination regimens, overall response rates have ranged from 42% to 100%. Complete responses of 3%-67% and partial responses of 33%-80% have been observed in first-line therapy. Furthermore, the median overall survival in @entity1 receiving topotecan in first-line therapy has ranged from approximately 8 months ( @entity5 ) to 20 months (limited-stage disease). The most frequent adverse events associated with topotecan-based regimens include grade 3/4 @entity1398 and @entity882 that often require the incorporation of growth factor support into the treatment regimen. Nonhematologic adverse events associated with topotecan-based combination regimens have been mild or primarily attributed to other agents in the combination. Alternative doses and schedules (3 consecutive days and weekly) are being explored because they appear to be associated with considerably less myelosuppression. Although several trials have established the feasibility and activity of topotecan in first-line therapy of @entity1 with @entity151 , randomized phase III studies with comparison to standard therapy will be required to confirm a potential role for this active agent and to determine the optimal dosing regimen.
