PURPOSE: @entity8202 is an orally active @entity11349 transferase inhibitor that specifically blocks farnesylation of proteins involved in growth-factor-dependent cell-signal-transduction pathways. We conducted a phase II study in 76 @entity1 with @entity0 . @entity1 AND METHODS: Two cohorts of @entity1 were recruited sequentially. The first cohort (n = 41) received a @entity400 [ @entity400 ] regimen of @entity8202 400 or 300 mg bid. The second cohort (n = 35) received 300 mg bid in a cyclical regimen of 21 days of treatment followed by 7 days of rest (intermittent dosing [ID]). RESULTS: In the @entity400 cohort, four @entity1 (10%) had a partial response (PR) and six @entity1 (15%) had stable disease at > or = 24 weeks ( @entity168 ). In the ID cohort, five @entity1 (14%) had a PR and three @entity1 (9%) had prolonged @entity168 . The first six @entity1 in the @entity400 cohort treated at 400 mg bid all developed grade 3 to 4 @entity1398 , so the subsequent 35 @entity1 were treated at 300 mg bid. The incidence of @entity1503 was significantly lower in the ID than in the @entity400 (300-mg bid) cohort: grade 3 to 4 @entity1398 (14% v 43%; P =.016) and grade 3 to 4 @entity882 (3% v 26%; P =.013). One @entity1 in the ID cohort developed grade 2 to 3 @entity2359 compared with 15 @entity1 in the @entity400 cohort (3% v 37%; P =.0004). CONCLUSION: The farnesyl transferase inhibitor @entity8202 has demonstrated clinical activity in @entity1 with metastatic @entity0 , and the ID regimen has a significantly improved therapeutic index compared with the @entity400 regimen.

Phase II study of the efficacy and tolerability of two dosing regimens of the farnesyl transferase inhibitor, @entity8202 , in XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient', 'PATIENTS'] @entity11349 :: ('CHEBI:24017', 'Chemical') :: ['farnesyl'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancer', 'advanced breast cancer'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity168 :: ('MESH:D029461', 'Disease') :: ['SD'] @entity8202 :: ('MESH:C402769', 'Chemical') :: ['R115777'] @entity1503 :: ('MESH:D006402', 'Disease') :: ['hematologic toxicity'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['neutropenia'] @entity400 :: ('MESH:D014202', 'Disease') :: ['continuous dosing', 'CD'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity']
@entity0 :: (MESH:D001943,Disease) :: ['advanced breast cancer']
