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

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 increasing Topo I levels during a daily x 5 schedule of treatment with topotecan.

• Authors: Nadja E Schoemaker, Virginie M M Herben, Laurina A de Jong, Robert C A M van Waardenburg, Dick Pluim, Wim W ten Bokkel Huinink, Jos H Beijnen, Jan H M Schellens
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 13 Issue 1 Pg. 87-91 (Jan 2002) ISSN: 0959-4973 [Print] England
• PMID: 11914645 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Granulocyte Colony-Stimulating Factor
• Topotecan
• DNA Topoisomerases, Type I
• Paclitaxel
• Cisplatin

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Biomarkers (blood)
• Cisplatin (administration & dosage, adverse effects)
• DNA Topoisomerases, Type I (metabolism)
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage, adverse effects)
• Humans
• Leukocytes (enzymology)
• Middle Aged
• Ovarian Neoplasms (blood, drug therapy)
• Paclitaxel (administration & dosage, adverse effects)
• Topotecan (administration & dosage, adverse effects)
• Tumor Cells, Cultured (drug effects)