UNASSIGNED: @entity1138 ( @entity1139 ) has potent @entity137 but cumulative @entity137 limits widespread use. In animals, pegylated liposomal @entity1138 lipid-based prodrug (PL-MLP) was well tolerated and more effective than free @entity1139 . We evaluated PL-MLP in @entity1 with @entity5 . Twenty-seven @entity1 were treated in escalating dose cohorts of 0.5-3.5  mg/kg (equivalent to 0.15-1.03  mg/kg @entity1139 ) every 4  weeks for up to 12 cycles, unless disease progression or unacceptable @entity137 occurred. Pharmacokinetics were assessed during cycles 1 and 3. Per protocol maximum tolerated dose was not reached at 3.5  mg/kg. However, prolonged @entity882 developed after repeated doses of 3  mg/kg or cumulative doses of 10-12  mg/kg. Dose-related grade 3 or higher adverse events included @entity1295 , @entity417 , and decreased platelets. Cmax and AUC0-    increased linearly over the dose range 0.5-2.0  mg/kg, and greater than linearly from 2.5 to 3.5  mg/kg; there were no significant differences in clearance of MLP between cycles 1 and 3. Median t1/2 was 23  h among dose cohorts, with no trend by dose or cycle. One @entity1 had a partial response. Stable disease was observed in 10 @entity1 across all dose levels. PL-MLP has a long circulation time, was well tolerated, and can be administered to heavily pretreated @entity1 at a single dose of 3.0  mg/kg and cumulative dose of 10-12  mg/kg before development of prolonged @entity882 ; this is nearly threefold the equivalent dose of @entity1139 tolerated historically. This formulation may be active in a variety of @entity5 types and is better tolerated than free @entity1139 .

Pegylated liposomal @entity1138 prodrug enhances tolerance of XXXX : a phase 1 study in advanced solid @entity5 @entity1 .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity', 'cytotoxicity'] @entity417 :: ('MESH:D000740', 'Disease') :: ['anemia'] @entity882 :: ('MESH:D013921', 'Disease') :: ['thrombocytopenia'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'advanced cancer'] @entity1138 :: ('MESH:D016685', 'Chemical') :: ['mitomycin C', 'Mitomycin C'] @entity1295 :: ('MESH:D005221', 'Disease') :: ['fatigue'] @entity1139 :: ('CHEBI:27504', 'Chemical') :: ['MMC']
@entity1138 :: (MESH:D016685,Chemical) :: ['mitomycin C']
