Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel–cisplatin–topotecan in a phase I study
作者:
Nadja Schoemaker,
Virginie Herben,
Laurina de Jong,
Robert van Waardenburg,
Dick Pluim,
Wim ten Bokkel Huinink,
Jos Beijnen,
Jan Schellens,
期刊:
Anti-Cancer Drugs
(OVID Available online 2002)
卷期:
Volume 13,
issue 1
页码: 87-91
ISSN:0959-4973
年代: 2002
出版商: OVID
关键词: Pharmacokinetics;topoisomerase I;topotecan;Western blotting;white blood cells
数据来源: OVID
摘要:
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.
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