RT Journal Article
SR Electronic
T1 Pharmacokinetics and Metabolism of Irinotecan Combined with Capecitabine in Patients with Advanced Colorectal Cancer
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2985
OP 2990
VO 25
IS 4
A1 MARTIN CZEJKA
A1 JOHANNES SCHUELLER
A1 KATHARINA HAUER
A1 EVA OSTERMANN
YR 2005
UL http://ar.iiarjournals.org/content/25/4/2985.abstract
AB Background: Irinotecan (CPT-11) in combination with 5-fluorouracil/folinic acid is used successfully for first-line treatment of metastatic colorectal cancer. Capecitabine (CCB) represents a very convenient alternative to 5-fluorouracil, either as single agent or in a combination of regimens acting synergistically and with the potential to further improve efficacy. Both CPT-11 and CCB need to be activated by human carboxyl esterases, therefore a probable pharmacokinetic drug interaction was checked. Patients and Methods: Ten patients suffering from advanced colorectal cancer were enrolled in this trial. CPT-11 was administered as a 30-min i.v.-infusion (70 mg/m2) weekly. CCB was given p.o. twice daily for two weeks (2,000 mg/m2 daily) starting the day after the first CPT-11 infusion. Plasma samples were analysed during/after the first (MONO) and third (CAPIRI) CPT-11 infusion. Results: CCB did not alter CPT-11 plasma disposition, and no significant changes in cmax, AUClast, Vdss and Cltot during CAPIRI treatment could be observed. However, co-administration of CCB appeared to decrease SN-38 (the cytotoxic CPT-1l metabolite) plasma concentrations during the first three hours after initiation of CPT-11 infusion, with strongly time-dependent plasma percentage differences between control and CAPIRI treatment (p<0.005, R=0.981). Co-administration of CCB also had a similar impact on the initial plasma disposition of SN-38gluc, but not on that of the APC metabolite. Conclusion: Overall, our findings indicate that, while the administration of CCB resulted in reversible lower formation rates of SN-38 and SN-38gluc, it did not have a significant impact on CPT-11 pharmacokinetics. Copyright© 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved