Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study

Academic Article

Abstract

  • Topotecan stabilizes the topoisomerase I (Topo I) cleavable complex. We measured Topo I levels in white blood cells of patients with ovarian cancer treated with topotecan. Topotecan was given i.v. daily × 5 q 3 weeks in combination with paclitaxel (1 day before topotecan) and cisplatin (just prior topotecan). Our aim was to correlate Topo I levels to pharmacokinetics and toxicity. Topo I levels were determined using Western blotting and were expressed relative to the Topo I level present in 10 μg cell lysate of the human IGROV1 ovarian cancer cell line. We found no correlation between Topo I levels and (non-)hematological toxicity. Topo I levels after the fifth topotecan infusion were significantly negatively correlated with the AUC of topotecan (R=-0.64, p=0.026), in contrast with Topo I levels prior to (R=-0.25, p=0.4) and after (R=-0.30, p=0.3) the first topotecan infusion. Topo I levels after the fifth topotecan infusion (48±27%, mean±SD) were higher than Topo I levels prior to and after the first topotecan infusion (3.0±4.7 and 2.7±3.6%, respectively) (p=0.001). In conclusion, we detected a significant inverse correlation between Topo I level and topotecan AUC at day 5, and we found increasing Topo I levels during a daily × 5 schedule of treatment with topotecan. © 2002 Lippincott Williams & Wilkins.
  • Published In

  • Anti-Cancer Drugs  Journal
  • Digital Object Identifier (doi)

    Author List

  • Schoemaker NE; Herben VMM; De Jong LA; Van Waardenburg RCAM; Pluim D; Ten Bokkel Huinink WW; Beijnen JH; Schellens JHM
  • Start Page

  • 87
  • End Page

  • 91
  • Volume

  • 13
  • Issue

  • 1