Purpose: We sought to investigate the safety and efficacy of @entity136 , @entity900 , and @entity9433 (GCL) as neoadjuvant therapy in @entity1 with @entity150 ( @entity150 ) planned for radical cystectomy. Materials and Methods: Four cycles of GCL were administered as neoadjuvant therapy for @entity1 with @entity150 . Although initially designed as a phase II efficacy study with a primary endpoint of pathologic complete response at the time of radical cystectomy, the dose selected for investigation proved excessively toxic. A total of 6 @entity1 were enrolled. Results: The initial 4 @entity1 received @entity136 1000 mg/m2 intravenously on days 1 and 8 and @entity900 70 mg/m2 intravenously on day 1 of each 21-day treatment cycle. @entity9433 was administered as 1000 mg orally daily starting one week prior to the initiation of cycle 1 of GC and continuing until the completion of cycle 4 of GC. These initial doses were poorly tolerated, and the final 2 enrolled @entity1 received a reduced @entity9433 dose of 750 mg orally daily. However, reduction of the @entity9433 dose did not result in improved tolerance or drug-delivery, and the trial was terminated early due to excessive @entity137 . Grade 3/4 @entity137 included @entity294 (33%), @entity390 / @entity391 (33%), and @entity882 (33%). Conclusion: The addition of @entity9433 to GC as neoadjuvant therapy for @entity150 was limited by excessive treatment-related @entity137 . These findings highlight the importance of thorough dose-escalation investigation of combination therapies prior to evaluation in the neoadjuvant setting, as well as the limitations of determination of maximum tolerated dose for novel targeted combination regimens.

@entity900 , XXXX , and @entity9433 as Neoadjuvant Therapy for Muscle-Invasive @entity150 .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity9433 :: ('MESH:C490728', 'Chemical') :: ['lapatinib', 'Lapatinib'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity294 :: ('MESH:D003967', 'Disease') :: ['diarrhea'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity150 :: ('MESH:D001749', 'Disease') :: ['MIBC', 'muscle-invasive bladder cancer'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine']
@entity136 :: (MESH:C056507,Chemical) :: ['Gemcitabine']
