Ss. Agarwala et al., EVALUATION OF THE COMBINATION OF VINBLASTINE AND QUINIDINE IN PATIENTS WITH METASTATIC RENAL-CELL CARCINOMA - A PHASE-I STUDY, American journal of clinical oncology, 18(3), 1995, pp. 211-215
Quinidine is known to inhibit p-glycoprotein and enhance the activity
of vinblastine against cultured renal carcinoma cells. We have combine
d quinidine and vinblastine in a Phase I trial in patients with metast
atic renal cell carcinoma. Twenty-three patients were entered. Prior t
reatment included nephrectomy (15 patients), radiation (1 patient) and
interferons (8 patients), Cohorts of patients were treated at one of
three quinidine dose levels (100, 200, and 400 mg); one patient receiv
ed 300 mg. Quinidine was given orally 4 times daily starting 3 days pr
ior to the first dose of vinblastine of 5 mg/m(2) intravenously given
once a week. Hematologic parameters, EKG, and quinidine levels were mo
nitored weekly. Mean quinidine levels in each dose tier were 1.58, 2.5
9, and 4.24 mu g/ml, respectively. The dose-limiting toxicity was leuk
openia, which necessitated dose interruptions in 16 patients. The mean
nadir WBC count (X10(9)/L) was 3.47, 2.3, and 1.73 in each dose tier,
respectively. Corresponding values for the mean maximum decrease in W
BC count from baseline were 3.85, 5.86, and 6.53, respectively. There
was a trend for leukopenia to become more severe with increasing doses
of quinidine. Other toxicities included mild nausea and vomiting in a
ll patients, and hypotension and paralytic ileus in one patient each.
No cardiac toxicity was observed. One patient had a complete remission
and 4 patients had stable disease. We conclude that quinidine and vin
blastine may be administered together safely in a clinical setting, wi
th leukopenia being dose-limiting. Further studies are needed to deter
mine any therapeutic advantage over vinblastine alone.