A phase I and pharmacokinetic comparison of hepatic arterial and peripheral vein infusions of XXXX for @entity96 .

@entity1 @entity137 @entity96 @entity189 @entity3194 @entity157 @entity1431 @entity14 @entity11887 @entity221
@entity11887 ( @entity11887 ) was administered to five @entity1 with @entity96 (one case of @entity157 , two of @entity189 of unknown primary, two of metastatic @entity14 ). Under fluoroscopic guidance, percutaneous hepatic venous catheters were placed in five @entity1 and percutaneous hepatic arterial catheters in four. A fifth @entity1 's hepatic arterial catheter was implanted at laparotomy. Hepatic plasma flow was estimated by the Fick principle using peripheral vein @entity3194 infusion. On the first day of treatment, @entity1 received a 2- or 4 h hepatic arterial infusion of @entity11887 (130 mg/m2); peripheral venous, hepatic arterial, and hepatic venous timed blood samples were drawn during and for 18 h after drug infusion. On the second day of treatment, 2- or 4 h peripheral vein infusion of @entity11887 (130 mg/m2) was followed by the same blood sampling schedule. @entity1 were followed weekly for @entity137 . Four @entity1 received only one course of treatment, while a fifth received two courses. All @entity1 experienced @entity1431 (median nadir 2400/mm3; range 1400-2700/mm3). Two @entity1 developed @entity221 after drug infusion. No antitumor responses were observed. Plasma @entity11887 concentrations were measured by HPLC. Pharmacokinetic analyses are reported for four @entity1 . The hepatic extraction ratio ranged from 15% to 49%, hepatic plasma clearances were 0.029-0.353 1/min/m2; peripheral vein areas under the concentration-time curve during hepatic arterial infusion ranged from 35% to 50% of peripheral vein areas under the curve during peripheral vein infusion. We conclude that hepatic arterial @entity11887 infusion offers only modest pharmacokinetic advantage to the target organ or to the systemic circulation over peripheral vein infusion.
