EFFECTS OF CIS-DIAMMINEDICHLOROPLATINUM-II RELEASED FROM D,L-POLYLACTIC ACID IMPLANTED ADJACENT TO CORTICAL ALLOGRAFTS IN DOGS

This study was performed to determine the pharmacokinetics and local a nd systemic effects of cis-diamminedichloroplatinum II (cisplatin) rel eased from an open-cell polylactic acid polymer when the drug delivery device was placed adjacent to a cortical allograft. Bilateral interca lary femoral allografts were implanted in six normal beagles. The poly mer containing cisplatin was implanted adjacent to the allograft in on e femur, and the polymer without cisplatin was implanted adjacent to t he allograft in the contralateral femur. Systemic toxicity was evaluat ed clinically by hematologic and serum biochemistry tests and urinalys is. Healing of the allograft was monitored radiographically. The femor a were evaluated biomechanically, histologically, and histomorphometri cally 7.5 months after surgery. Total serum platinum levels were measu red by atomic absorption spectrophotometry, and pharmacokinetic parame ters were calculated. Healing was impaired slightly by the presence of the polymer with cisplatin, and systemic and local toxicity was mild and transient. After implantation of the polymer with cisplatin, the m ean peak total serum platinum concentration was low (1.71 +/- 0.19 mu g/ml). However, the area under the curve for total serum platinum conc entration versus time for the first 21 days was large (27,050 +/- 3,20 1 mu g.min/ml). When cisplatin was given as intravenous bolus at a dos e of 70 mg/m(2) to six other beagles, the mean peak total platinum con centration was 8.80 +/- mu g/ml and the area under the curve was 940.3 +/- 256.7 mu g.min/ml. These results indicate that a sustained releas e of cisplatin can be delivered safely from an open-cell polylactic ac id polymer. This device may be useful in the treatment of solid tumors .