PURPOSE: @entity9611 ( @entity5647 , @entity9611 ) has been shown to reverse @entity900 resistance in cell culture. This phase I study was performed to determine the maximally tolerated dose (MTD) and dose-limiting @entity137 of @entity5647 when administered by continuous intravenous infusion in combination with @entity900 (CDDP), and to evaluate the pharmacokinetics of @entity5647 in this setting. @entity1 AND METHODS: Entered in the study were 61 @entity1 with advanced, histologically confirmed @entity5 which were unresponsive to or for which no "standard" chemotherapeutic regimen existed. @entity5647 was administered as a 72-h infusion on days 1-3 and 14-16 of a 28-day cycle at dose levels from 400 through 14,364 mg/m(2) per day. CDDP at dose levels of 30, 45, or 60 mg/m(2) was administered at hour 36 of each @entity5647 infusion. The plasma pharmacokinetics of @entity5647 were determined in @entity1 treated at representative dose levels. RESULTS: Of the 61 @entity1 who completed 125 courses of therapy, 21 had stable disease for a median of four cycles (range two to eight), 33 progressed on therapy, and 7 were not assessable for response. The major observed @entity137 was myelosuppression. The MTD of @entity5647 was 8135 mg/m(2) per day when administered on this schedule. Escalation of CDDP did not result in additive @entity137 . The mean steady-state level of @entity5647 at the MTD was 44 microM (range 35-51 microM). CONCLUSIONS: Steady-state concentrations of @entity5647 increased with dose. The plasma levels achieved at the MTD exceeded those required for drug resistance reversal in vitro. The administration of CDDP had no effect on @entity5647 steady-state levels. The dose-limiting @entity137 of this drug combination is myelosuppression. @entity5647 may be useful in further studies utilizing combination therapy to achieve increased chemotherapy effectiveness.

Phase I study of @entity900 in combination with @entity9611 in the treatment of XXXX with advanced @entity5 .

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity9611 :: ('MESH:D015215', 'Chemical') :: ['Azidothymidine', 'zidovudine'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity5 :: ('MESH:D009369', 'Disease') :: ['malignancies'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity5647 :: ('CHEBI:10110', 'Chemical') :: ['AZT']
@entity1 :: (9606,Species) :: ['patients']
