@entity5 ( @entity151 ) is an @entity146 with a median survival of approximately 8 months. Although current combination chemotherapy regimens provide high initial @entity5 response rates, they have not translated into large gains in survival. Topotecan and @entity1311 have nonoverlapping mechanisms of action and are active agents in @entity151 . Additionally, these two agents demonstrate in vitro synergy in animal and @entity1 @entity5 models. We investigated the maximum tolerated dose of 3-day topotecan in combination with @entity1311 in previously untreated @entity1 with extensive @entity151 . Seventeen @entity1 were enrolled in an open-label, phase I, dose-escalation study and were treated with intravenous @entity1311 135-175 mg/m(2) over 1 hour on day 1, followed by intravenous topotecan 1.25-1.5 mg/m(2) over 30 minutes on days 1-3 of a 21-day course. Sixty-nine courses of therapy were administered with no delays due to hematologic @entity137 . Prophylactic hematologic support was required for 24% of @entity1 . The topotecan/ @entity1311 combination was well tolerated, with 24%, 12%, and 6% of @entity1 experiencing grade 3/4 @entity1398 , @entity417 , or @entity882 , respectively. Dose-limiting @entity1398 was seen in three of five @entity1 treated with topotecan 1.5 mg/m(2) and @entity1311 175 mg/m(2). Therefore, topotecan 1.5 mg/m(2) with @entity1311 135 mg/m(2) was determined to be the maximum tolerated dose. Of the 17 evaluable @entity1 , 53% achieved a partial response and 18% achieved stable disease. In summary, we have identified a regimen of topotecan 1.5 mg/m(2) and @entity1311 135 mg/m(2) that was well tolerated and active in this @entity1 group. Additional studies of @entity1945 and @entity1311 at these dose levels are needed to fully elucidate the efficacy of this combination in extensive @entity151 .

Phase I study of @entity1311 and topotecan for the first-line treatment of XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'patients', 'patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressive disease'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'Extensive-stage small cell lung cancer'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['paclitaxel'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity151 :: ('MESH:D055752', 'Disease') :: ['SCLC'] @entity1945 :: ('MESH:D019772', 'Chemical') :: ['topotecan']
@entity5 :: (MESH:D009369,Disease) :: ['extensive-stage small cell lung cancer']
