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Pharmacokinetic analysis of metronomic capecitabine in refractory metastatic colorectal cancer patients

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The aim of the present study was to assess the pharmacokinetics (PK) of metronomic capecitabine and its metabolites in a population of refractory metastatic colorectal cancer (mCRC) patients. Thirty-four patients (M/F, 22/12) with a diagnosis of mCRC received capecitabine 800 mg p.o. twice a day and cyclophosphamide 50 mg/day p.o. Blood samples were collected at baseline, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h and 5 h at day 1 after capecitabine administration. Plasma concentrations of capecitabine and its metabolites were measured by high performance liquid chromatography and the main PK parameters were calculated. Maximum plasma concentrations (Cmax) of capecitabine (11.51 ± 9.73 μg/ml) occurred at 0.5 h, whereas the Cmax of 5′-deoxy-5-fluorocytidine (5’-DFCR; 2.45 ± 2.93 μg/ml), 5′-deoxy-5-fluorouridine (5’-DFUR; 6.43 ± 8.2 μg/ml), and 5-fluorouracil (5-FU; 0.24 ± 0.16 μg/ml) were found at 1 h, 1.5 h and 1 h, respectively. Capecitabine, 5’-DFCR, 5’-DFUR and 5-FU AUCs at day 1 were 21.30 ± 10.78, 5.2 ± 4.6, 19.59 ± 3.83 and 0.66 ± 0.77 hxμg/ml, respectively. In conclusion, low doses of capecitabine were rapidly absorbed and extensively metabolized, achieving measurable plasma concentrations in a heavily pretreated population of patients.

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The authors wish to thank A. Di Paolo, R. Danesi, L. Salvatore, patients and their families for their participation to the study, which was funded by the Istituto Toscano Tumori (ITT).

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Correspondence to Guido Bocci.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Di Desidero, T., Orlandi, P., Fioravanti, A. et al. Pharmacokinetic analysis of metronomic capecitabine in refractory metastatic colorectal cancer patients. Invest New Drugs 36, 709–714 (2018).

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