Stability of cancer chemotherapeutic agents in a totally implanted drug-delivery system

Abstract

The stability and compatibility of serveral chemotherapeutic agents with an implantable infusion device were evaluated. The totally implantable drug delivery system can be placed subcutaneously in an ambulatory patient to permit the regional administration of antineoplastic drugs. The in vitro method of assessing the stability of three chemotherapeutic agents with the pumping device involved placing the pumps, filled with cytarabine, dichloromethotrexate, and vinblastine, in a 37 degree C water bath with mild agitation. Control solutions placed in amber vials were maintained under simulated physiological conditions. Samples (1 ml) were removed periodically, frozen at -20 degrees C and later toward and batch assayed by high pressure liquid chromatography to determine drug concentrations. An in vivo assessment of the stability of floxuridine was also conducted in five patients receiving intra-arterial hepatic infusions by the device. The concentrations placed in the pump were compared with the contractions removed at the time of refill. Cytarabine and dichloromethotrexate showed no appreciable drug decomposition in the control vials or the pump over the 15-day and 28-day study periods, respectively. Vinblastine underwent a 48% and 20% drugs loss in the pump and control, respectively, during a 14-day period. In the vivo assessment of floxuridine, less than 5% drug degradation was found for infusion times ranging from four to 12 days. Cytarabine, dichloromethothrexate, and floxuridine were stable and compatible with the implantable infusion evice, and vinblastine was found to be unstable. The compatibility of all agents with the infusion device should be evaluated before clinical application.