PURPOSE: To ascertain the maximum tolerated duration of infusion of @entity136 at 10 mg/m(2)/min in combination with @entity2664 at 12 mg/m(2) daily for 3 days in the treatment of @entity3052 . @entity1 AND METHODS: Thirty-four @entity1 were enrolled. Stratum I consisted of 26 @entity1 , median age 50 years (range, 25 to 71 years), with relapsed or @entity1778 . Stratum II contained eight @entity1 , median age 62.5 years (range, 38 to 83 years), who had received fewer than three cycles of myelotoxic therapy for @entity1860 or @entity2590 that had evolved into @entity1778 . @entity1 received @entity2664 at 12 mg/m(2) daily for 3 days. After the first @entity2664 dose, @entity136 was provided intravenously at 10 mg/m(2)/min with the duration adjusted by following a continuous reassessment model. RESULTS: Severe myelosuppression, and @entity3136 or @entity2910 were the most common hematologic and nonhematologic dose-limiting @entity137 . Several @entity1 developed @entity1398 , @entity390 , or @entity391 . In both strata, the maximum recommended duration of infusion of @entity136 was 12 hours (7,200 mg/m(2)). The mean steady-state concentration of @entity136 was 24.72 micromol/L and varied over a fivefold range among @entity1 . Overall response rates in this phase I trial for strata I and II were 42% and 63%, respectively. CONCLUSION: Prolonged-infusion @entity136 at a fixed dose rate of 10 mg/m(2)/min for 12 hours with 12 mg/m(2)/d @entity2664 for 3 days is a tolerable induction regimen and achieves plasma concentrations sufficient for maximal intracellular activation. @entity3136 or @entity2910 should be anticipated; however, this regimen may induce significant responses in @entity1 with @entity1778 .

Phase I evaluation of prolonged-infusion @entity136 with @entity2664 for relapsed or refractory XXXX .

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients', 'PATIENTS'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicities'] @entity3136 :: ('MESH:D013280', 'Disease') :: ['stomatitis', 'Stomatitis'] @entity390 :: ('MESH:D009325', 'Disease') :: ['nausea'] @entity2910 :: ('MESH:D004941', 'Disease') :: ['esophagitis'] @entity2664 :: ('MESH:D008942', 'Chemical') :: ['mitoxantrone'] @entity2590 :: ('MESH:D009190', 'Disease') :: ['myelodysplasia'] @entity391 :: ('MESH:D014839', 'Disease') :: ['vomiting'] @entity3052 :: ('MESH:D015470', 'Disease') :: ['acute leukemia'] @entity1778 :: ('MESH:D007938', 'Disease') :: ['leukemia', 'refractory leukemia', 'difficult-to-treat leukemias'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['febrile neutropenia'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['gemcitabine'] @entity1860 :: ('MESH:D015464', 'Disease') :: ['chronic myeloid leukemia']
@entity3052 :: (MESH:D015470,Disease) :: ['acute leukemia']
