Topoisomerase I levels in white blood cells of patients with ovarian cancer treated with paclitaxel-cisplatin-topotecan in a phase I study.
Anticancer Drugs
; 13(1): 87-91, 2002 Jan.
Article
en En
| MEDLINE
| ID: mdl-11914645
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.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
ADN-Topoisomerasas de Tipo I
/
Leucocitos
Límite:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
Anticancer Drugs
Asunto de la revista:
ANTINEOPLASICOS
Año:
2002
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido