| Autor: |
Schoemaker NE; Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands. APNSC@SLZ.nl, Herben VM, de Jong LA, van Waardenburg RC, Pluim D, ten Bokkel Huinink WW, Beijnen JH, Schellens JH |
| Jazyk: |
angličtina |
| Zdroj: |
Anti-cancer drugs [Anticancer Drugs] 2002 Jan; Vol. 13 (1), pp. 87-91. |
| DOI: |
10.1097/00001813-200201000-00010 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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