Phase II trial of @entity4562 in recurrent or metastatic XXXX .

@entity1 @entity137 @entity4562 @entity470 @entity5 @entity294 @entity3963 @entity669 @entity213
PURPOSE: The @entity470 ( @entity470 ) is a mediator of @entity213 ( @entity213 ) development. @entity4562 is an orally active, selective @entity470 @entity669 kinase inhibitor. This phase II study sought to explore the activity, @entity137 , and pharmacodynamics of @entity4562 in @entity213 . @entity1 AND METHODS: @entity1 with recurrent or metastatic @entity213 were enrolled through the University of Chicago Phase II Consortium. @entity1 were allowed no more than one prior therapy for recurrent or metastatic disease and were treated with single-agent @entity4562 500 mg/d. @entity1 @entity5 biopsies were obtained and stained immunohistochemically for @entity470 , @entity3963 ( @entity3963 ), and phosphorylated @entity3963 (p-ERK). Study end points included response rate, time to progression, median survival, and inhibition of p-ERK. RESULTS: Fifty-two @entity1 were enrolled (40 male and 12 female) with a median age of 59 years (range, 34 to 84 years). Fourteen @entity1 received @entity4562 through a feeding tube. Half the cohort received @entity4562 as second-line therapy. Forty-seven @entity1 were assessable for response, with an observed response rate of 10.6% and a disease control rate of 53%. Median time to progression and survival were 3.4 and 8.1 months, respectively. The only grade 3 @entity137 encountered was @entity294 in three @entity1 . Performance status and development of @entity137 were found to be strong predictors of response, progression, and survival. Ten biopsy samples were assessable and revealed no significant change in @entity470 or p-ERK expression with @entity4562 therapy. CONCLUSION: @entity4562 has single-agent activity and is well tolerated in refractory @entity213 . In contrast to other reports, development of @entity137 was a statistically significant predictor of response and improved outcome.
