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dc.contributor.authorde Man, Femke M
dc.contributor.authorvan Eerden, Ruben A G
dc.contributor.authorvan Doorn, Gerdien M
dc.contributor.authorOomen-de Hoop, Esther
dc.contributor.authorKoolen, Stijn L W
dc.contributor.authorOlieman, Joanne F
dc.contributor.authorde Bruijn, Peter
dc.contributor.authorVeraart, Joris N
dc.contributor.authorvan Halteren, Henk K
dc.contributor.authorSandberg, Yorick
dc.contributor.authorMoelker, Adriaan
dc.contributor.authorIJzermans, Jan N M
dc.contributor.authorLolkema, Martijn P
dc.contributor.authorvan Gelder, Teun
dc.contributor.authorDollé, Martijn E T
dc.contributor.authorde Bruin, Ron W F
dc.contributor.authorMathijssen, Ron H J
dc.date.accessioned2020-11-12T12:39:14Z
dc.date.available2020-11-12T12:39:14Z
dc.date.issued2020-10-29
dc.identifier.issn1532-6535
dc.identifier.pmid33119892
dc.identifier.doi10.1002/cpt.2094
dc.identifier.urihttp://hdl.handle.net/10029/624495
dc.description.abstractPreclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor effect. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this cross-over trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5 days of PCR (~30% caloric and ~70% protein restriction) during the 1st cycle and a 2nd cycle preceded by a normal diet (ND) or vice versa. Pharmacokinetic blood sampling and biopsies of both healthy liver (HL) and liver metastasis (LM) were performed. Primary endpoint was the relative difference in geometric means for the active metabolite SN-38 concentration in HL analyzed by a linear mixed model. No significant differences were seen in irinotecan (+16.8%, P=0.22) and SN-38 (+9.8%, P=0.48) concentrations between PCR and ND in HL, as well as in LM (irinotecan: -38.8%, P=0.05 and SN-38: -13.8%, P=0.50). PCR increased irinotecan plasma AUC0-24h with 7.1% (P=0.04) compared to ND, while the SN-38 plasma AUC0-24h increased with 50.3% (P<0.001). Grade ≥3 toxicity was not increased during PCR vs ND (P=0.69). No difference was seen in neutropenia grade ≥3 (47% vs 32% P=0.38), diarrhea grade ≥3 (5% vs 21% P=0.25) and febrile neutropenia (5% vs 16% P=0.50) during PCR vs ND. In conclusion, plasma SN-38 exposure increased dramatically after PCR, while toxicity did not change. PCR did not alter the irinotecan and SN-38 exposure in HL and LM. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan.en_US
dc.language.isoenen_US
dc.subjectdieten_US
dc.subjectintra-tumoralen_US
dc.subjectirinotecanen_US
dc.subjectpharmacokineticsen_US
dc.subjectprotein and calorie restrictionen_US
dc.titleEffects of protein and calorie restriction on the metabolism and toxicity profile of irinotecan in cancer patients.en_US
dc.typeArticleen_US
dc.identifier.journalClin Pharnacol Ther 2021: 109(5):1304-13en_US
dc.source.journaltitleClinical pharmacology and therapeutics


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