PHASE-I STUDY OF WR-2721 AND CARBOPLATIN

Because WR-2721 reduces the toxicity of cisplatin and carboplatin in p reclinical systems, we have treated 35 patients in a phase I study of WR-2721 and carboplatin. As the plasma half-life of WR-2721 is short r elative to that of carboplatin, WR-2721 was administered in two divide d doses. This schedule produced acceptable toxicity in 24 patients tre ated with carboplatin 400 mg/m2 and escalating doses of WR-2721. In th e subsequent 11 patients, WR-2721 was fixed at 740 mg/m2/dose and the dose of carboplatin was escalated. With WR-2721, grade 3-4 thrombopeni a (platelets <50 x 10(9)/l) was produced in 4/5 patients treated with carboplatin 625 mg/m2 and in 1/6 patients treated with carboplatin 500 mg/m2. Carboplatin pharmacokinetic parameters in 4 patients were simi lar to those reported for carboplatin alone. These results suggest tha t WR-2721 might increase the maximum tolerated dose of carboplatin fro m 400 to 500 mg/m2.