BACKGROUND: The authors investigated the maximum tolerated dose (MTD) and dose limiting @entity137 (DLT) associated with the addition of a biomodulating dose of @entity136 to an established regimen of @entity1260 and @entity632 as part of a program to explore the potential of low-dose @entity136 to modulate the activity of alkylating agents. METHODS: A Phase I trial was carried out in a population of @entity1 with @entity150 for whom no standard therapy was available. Doses of @entity1260 and @entity632 were held fixed at 2 g/m(2) for 4 days and 20 mg/m(2) for 3 days, respectively. @entity136 was given on Day 2 and Day 4 at doses of 90 mg/m(2), 150 mg/m(2), and 200 mg/m(2) per dose. RESULTS: A total of 18 @entity1 received 53 courses of therapy. Myelosuppression was dose limiting. Nonhematologic @entity137 also was significant, with 10 of 18 @entity1 experiencing @entity137 of Grade 3 or greater. For previously untreated @entity1 with an intact performance status, the MTD for @entity136 in this context was at least 150 mg/m(2) per dose. According to an intent-to-treat analysis, 11 of 18 @entity1 demonstrated a clinically significant response to this regimen. CONCLUSIONS: The regimen of @entity1260 and @entity632 with the addition of @entity136 was significantly toxic but has promising activity. Based on the observed activity and the generally reversible nature of the @entity137 , the authors have initiated a Phase II trial of this regimen in @entity1 with untreated, metastatic @entity189 .

@entity136 modulation of alkylator therapy: a phase I trial of escalating XXXX added to fixed doses of @entity1260 and @entity632 .

@entity632 :: ('MESH:D004317', 'Chemical') :: ['doxorubicin'] @entity1 :: ('9606', 'Species') :: ['patients'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity189 :: ('MESH:D002277', 'Disease') :: ['urothelial carcinoma'] @entity150 :: ('MESH:D001749', 'Disease') :: ['bladder or pelvic carcinoma'] @entity1260 :: ('MESH:D007069', 'Chemical') :: ['ifosfamide'] @entity136 :: ('MESH:C056507', 'Chemical') :: ['Gemcitabine', 'gemcitabine']
@entity136 :: (MESH:C056507,Chemical) :: ['gemcitabine']
