The clinical pharmacokinetics of
vinblastine administered by continuous 5-day infusion (3 mg/m2/day) was studied in 12 patients with primary
testicular cancer. Serum
vinblastine concentrations were determined by radioimmunoassay on serum collected over a 10-day period. Steady-state
vinblastine concentrations were achieved within 60 to 108 hours (median, 72 hours).
Vinblastine pharmacokinetics were analyzed and correlated to hematologic and nonhematologic toxicity. Hematologic toxicity was severe (
granulocytopenia of less than 500/microL) in all patients; however, no correlation of
vinblastine pharmacokinetics to duration of
granulocytopenia or nadir was noted. Nonhematologic toxicity, however, showed a direct correlation to steady-state
vinblastine concentrations. Two distinct groups of patients were identified by a toxicity score evaluating nonhematologic toxicity: as low (group A) or high (group B). The toxicity score was calculated for each patient based on accumulated toxicity during the course of treatment. The mean toxicity score for all patients was 7.11 and for groups (A and B) it was 4.0 and 9.6, respectively (P = .02). Steady-state
vinblastine concentration for each patient was compared with toxicity where the mean steady-state
vinblastine concentration was 7.3 ng/mL for all patients, and 5.8 ng/mL and 8.5 ng/mL for groups A and B, respectively (P = .01). These steady-state
vinblastine concentrations correlated directly with the mean toxicity scores revealing that patients with high steady-state
vinblastine concentrations demonstrated more nonhematologic toxicity. Application of these data to pharmacokinetically directed studies are warranted to investigate this relationship and designate dosages of
vinblastine to avoid excessive toxicity.