Abstract
Purpose
Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 concentrations may have been increased in subjects receiving BV. However, the mechanism underlying such increase remains unclear, and the difference might be caused by an imbalance between the two arms and a possible inter-subject variability of CPT-11 metabolism. Within-subject comparisons were used to evaluate the effect of BV on advanced colorectal cancer patients when administered with the FOLFIRI regimen as second-line chemotherapy.
Methods
Ten advanced colorectal cancer patients received the FOLFIRI regimen every 2 weeks. At cycle 1, BV was administered following FOLFIRI administration to allow baseline pharmacokinetic (PK) analysis of CPT-11 and its metabolites. From cycle 2, BV was administered just before FOLFIRI administration. Plasma samples were collected under the same condition (at cycle 3).
Results
There were no significant differences in the C max and AUC0-∞ of CPT-11, SN-38, and SN-38G between cycle 1 (without BV) and cycle 3 (with BV). PK parameters of CPT-11, SN-38, and SN-38G were not significantly affected by BV. There were no significant differences in the changes in the AUC ratio of CPT-11 to SN-38 between cycles 1 and 3, as well as in the ratio of SN-38 to SN-38G.
Conclusion
BV does not affect the plasma concentration of CPT-11 and its metabolites on FOLFIRI regimen.
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Acknowledgments
We thank Ms. Hideko Morita and Makiko Shinogi for their help in collecting and organizing the clinical samples.
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Horita, Y., Yamada, Y., Hirashima, Y. et al. Effects of bevacizumab on plasma concentration of irinotecan and its metabolites in advanced colorectal cancer patients receiving FOLFIRI with bevacizumab as second-line chemotherapy. Cancer Chemother Pharmacol 65, 467–471 (2010). https://doi.org/10.1007/s00280-009-1051-4
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DOI: https://doi.org/10.1007/s00280-009-1051-4