A pilot study of low dose hydroxyurea as a novel resistance modulator in metastatic renal cell cancer

Mechanisms of chemoresistance in renal cell carcinoma include P-glycoprotei n, overexpression of multidrug resistance-1 (mdr1) gene, and unstable chrom osomal aberrations. In vitro exposure of resistant tumor cells to low dose hydroxyurea causes loss of chromosomal aberrations, decrease in the mdr1 ge ne copies, and increased sensitivity to vinblastine, Patients received continuous hydroxyurea 500 mg every Monday, Wednesday and Friday. Vinblastine 5 mg/m(2) was given intravenously on days 1 and 8 ever y 21 days. Seventeen patients with a median age of 63 (range 40-80) receive d a median of 3 courses of vinblastine (range 1-14), Toxicities included: g reater than or equal to grade 3 non-hematologic toxicity (1) and febrile ne utropenia (2), No treatment related mortality occurred, Three patients (17. 6%) had partial responses. The median survival was 38.0 weeks (95% CI = 26. 9-49.1 weeks). The addition of hydroxyurea given at the dose of 500 mg orally three times weekly had no major impact on the expected antitumor effect of vinblastine.