Phase I trial of an implanted battery-powered, programmable drug delivery system for continuous doxorubicin administration.

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Abstract
A 2nd generation, implantable drug administration device (DAD, Medtronic, Inc., Minneapolis [Minnesota, USA]) which contains a 20-ml drug reservoir, a lithium-thionylchloride battery, a peristaltic roller pump, a microprocessor circuit and an acoustic transducer has entered clinical trials. After surgical placement, drug is entered into and removed from the DAD percutaneously through a Silastic fill port using a standard gauge needle and syringe. The pump is noninvasively programmed, using a hand-held telemetry wand, to administer the drug in a continuous infusion, bolus, or bolus-delay mode. Because of the apparent improved therapeutic index of continuous-infusion doxorubicin (CID), a phase I trial of the Medtronic DAD with CID was begun. Thirteen pumps in 13 patients have functioned for a median of 153 days (range, 11-395 days), with 1 pump still functioning. Four pumps ceased function at 170, 278, 331 and 370 days, respectively; there was a catheter-tip clot on 1 of the pumps that later malfunctioned. All other pumps functioned until the death of the respective patients. In 84 pump refills, without drug extravasation, the median drug delivery error (actual residual vol-calculated residual vol/calculated residual vol .times. 100%) was 14%. Doxorubicin was compatible with all components of the drug pathway and did not significantly decompose during 2 wk in the drug reservoir. The starting dose of CID was 2.0 mg/m2 per d [day], and the maximum tolerated dose was 4.1 mg/m2 per d (range, 3.5-5.5). A median cumulative doxorubicin dose of 244 mg/m2 per patient (range, 10-583 mg/m2) has been infused. Stomatitis was dose limiting in 7 of 10 evaluable patients, and tumor regression occurred in 2 of 10 evaluable patients. The Medtronic DAD is a safe and reliable device that allows CID.