PURPOSE: To determine the maximum-tolerated dose (MTD) of @entity632 when given in combination with @entity900 and the multidrug-resistance (MDR) modulator valspodar and the remission rate induced by this combination in @entity1 with @entity902 - and @entity4349 -resistant @entity43 . @entity1 AND METHODS: Fifty-nine @entity1 who had failed prior @entity902 - and @entity4349 -based chemotherapy were enrolled. During the dose-finding phase, @entity1 received a loading dose of valspodar (1.5 or 2 mg/kg) via 2-hour intravenous (IV) infusion on day 1 and continuous IV infusion (CIVI) of @entity7358 (2, 4, or 10 mg/kg/d) over 3 days. @entity632 (starting from 20 up to 50 mg/m(2)) and @entity900 (50 mg/m(2)) were administered via 15- to 20-minute IV infusions on day 3. During the efficacy phase, @entity1 received at least two treatment cycles unless @entity137 was unacceptable, and responding @entity1 and those with stable disease received four to six cycles. RESULTS: All @entity1 completed at least one cycle of combined treatment. The MTD of @entity632 was determined to be 35 mg/m(2) when administered with valspodar at 2 mg/kg loading dose and 10 mg/kg/d CIVI plus 50 mg/m(2) @entity900 . At these doses, valspodar blood concentrations known to reverse MDR in vitro were reached in all @entity1 . Valspodar was well tolerated at all dose levels. Dose-limiting @entity137 of the combination were primarily hematologic and included @entity1398 and prolonged @entity1210 . The addition of valspodar to the treatment did not worsen @entity900 -related @entity137 . Among 33 @entity1 treated at the MTD for @entity632 , one (3%) had a complete response, and four (12%) had a partial response. An additional seven @entity1 experienced a stabilization of their previously progressive disease. The survival rates at 6 and 12 months were 59% and 19%, respectively. CONCLUSION: Valspodar can be safely coadministered with @entity632 and @entity900 . Although the regimen used in this trial produced renewed responses in @entity1 with heavily pretreated, refractory @entity43 , the value of valspodar in reversing resistance mediated by @entity1262 remains to be determined.

Phase I/II trial of the multidrug-resistance modulator valspodar combined with @entity900 and @entity632 in refractory XXXX .

@entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin', 'Doxorubicin'] @entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancer'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'toxicities'] @entity1262 :: ('5243', 'Gene') :: ['P-glycoprotein'] @entity4349 :: ('CHEBI:48120', 'Chemical') :: ['anthracycline'] @entity900 :: ('MESH:D002945', 'Chemical') :: ['cisplatin'] @entity1398 :: ('MESH:D009503', 'Disease') :: ['febrile neutropenia'] @entity7358 :: ('MESH:C070272', 'Chemical') :: ['valspodar'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum'] @entity1210 :: ('MESH:C536227', 'Disease') :: ['leucopenia']
@entity43 :: (MESH:D010051,Disease) :: ['ovarian cancer']
