Continuous @entity1891 infusion as part of a high dose chemoradiotherapy regimen: drug kinetics and XXXX .

@entity1 @entity1944 @entity137 @entity242 @entity648 @entity425 @entity925 @entity348 @entity1891 @entity521 @entity490 @entity1142 @entity2359 @entity6085
A 5-day continuous infusion of @entity1891 (VCR; total dose 4 mg/m2) has been given as part of a high-dose chemoradiotherapy regimen with bone marrow transplantation. Evidence of @entity2359 , such as @entity425 , paraesthesia and @entity1944 , was evaluated prospectively in nine @entity1 . Five @entity1 had advanced @entity521 and four, relapsed @entity242 , and all had responded to initial conventional-dose therapy. VCR was combined with high-dose melphalan (180 mg/m2) and fractionated @entity348 . Plasma concentrations of VCR were measured by radioimmunoassay during and up to 24 h after the infusion. Serum and urine electrolytes and liver function tests were measured during VCR treatment and at regular intervals thereafter. VCR concentration at 1 h ranged from 1.8 to 10.9 (median 6.6) ng/ml, and a steady state was achieved by 13-30 h (median 16 h). Levels above 1 ng/ml were maintained throughout the 5-day period with a mean steady-state concentration of 1.7 ng/ml (range 1.3-2.15). After cessation of the infusion, serum concentrations fell to below 0.25 ng/ml within 24 h. @entity490 occurred in one @entity1 , but neither @entity1142 nor ileus was seen. In two @entity1 severe @entity925 occurred in the lower limbs towards the end of the infusion. Significant electrolyte problems did not occur and, in particular, there was no evidence of @entity6085 . Transient increases in liver enzymes were common but @entity648 was not elevated during the period of monitoring. This regimen allows a two-fold escalation in the dose of VCR to be administered, producing sustained high serum drug levels without major @entity137 .
