Efficacy of the farnesyl transferase inhibitor XXXX in chronic myeloid leukemia and other hematologic malignancies.

@entity1 @entity137 @entity390 @entity1910 @entity7 @entity8202 @entity1582 @entity1897 @entity4018 @entity381 @entity1860
We investigated the clinical activity of the farnesyl transferase inhibitor @entity8202 in 22 @entity1 with @entity1860 ( @entity1860 ) in chronic, accelerated, or blastic phase and in 8 @entity1 with @entity4018 ( @entity4018 ) and 10 @entity1 with @entity1582 ( @entity1582 ). @entity8202 was administered at 600 mg orally twice daily for 4 weeks every 6 weeks. Seven @entity1 with @entity1860 (6 in chronic phase, 1 in advanced phase) achieved complete or partial hematologic response. Four of them had a minor cytogenetic response. Responses were transient, with a median duration of 9 weeks (range, 3-23 weeks). Two @entity1 discontinued therapy because of @entity137 while in complete hematologic response. Two @entity4018 @entity1 had a significant decrease in @entity381 , one had normalization of white blood cell count and differential, and one became transfusion independent. One @entity1 with @entity1582 had a reduction in monoclonal protein of 34%. Adverse events included @entity390 in 22 @entity1 (55%; all grade 2 or lower) and fatigue in 19 (48%; grade 3 or higher in 1). Other grade 3 or 4 @entity137 included @entity1910 (4 @entity1 , 10%), @entity1897 (2 @entity1 , 5%), and liver @entity137 (2 @entity1 , 5%). @entity1 who responded to therapy had significantly higher plasma @entity7 ( @entity7 ) concentrations prior to treatment than nonresponders. Plasma concentrations decreased significantly during therapy among responders. @entity8202 showed clinical activity in @entity1 with @entity1860 and @entity4018 . The effect on @entity7 needs to be further investigated to determine whether this might be a possible mechanism of action of @entity8202 .
