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

Anti-cancer Drugs
Nadja E SchoemakerJ H Schellens

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 x 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 microg 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 increa...Continue Reading

References

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Citations

Jan 30, 2007·Expert Opinion on Pharmacotherapy·Leslie M Randall-Whitis, Bradley J Monk
Dec 20, 2007·The Journal of Pharmacy and Pharmacology·Daniel MorenoMaría J Garrido
Jun 8, 2012·PloS One·Fred E IndigVilhelm A Bohr
Aug 12, 2014·World Journal of Gastroenterology : WJG·Mariusz Panczyk
Jun 18, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·David S BossJan H M Schellens

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