{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T07:21:46Z","timestamp":1787383306628,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T00:00:00Z","timestamp":1607212800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:p>Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics and toxicity. In this crossover trial, patients with liver metastases of solid tumors were included and randomized to treatment with irinotecan preceded by 5\u00a0days of PCR (~\u00a030% caloric and ~\u00a070% protein restriction) during the first cycle and a second cycle preceded by a normal diet or <jats:italic>vice versa<\/jats:italic>. Pharmacokinetic blood sampling and biopsies of both healthy liver and liver metastases were performed. The primary end point was the relative difference in geometric means for the active metabolite SN\u201038 concentration in healthy liver analyzed by a linear mixed model. No significant differences were seen in irinotecan (+\u00a016.8%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.22) and SN\u201038 (+\u00a09.8%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.48) concentrations between PCR and normal diet in healthy liver, as well as in liver metastases (irinotecan: \u221238.8%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.05 and SN\u201038: \u221213.8%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.50). PCR increased irinotecan plasma area under the curve from zero to 24 hours (AUC<jats:sub>0\u201324h<\/jats:sub>) with 7.1% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.04) compared with normal diet, whereas the SN\u201038 plasma AUC<jats:sub>0\u201324h<\/jats:sub> increased with 50.3% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Grade \u2265\u00a03 toxicity was not increased during PCR vs. normal diet (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.69). No difference was seen in neutropenia grade \u2265\u00a03 (47% vs. 32% <jats:italic>P<\/jats:italic>\u00a0=\u00a00.38), diarrhea grade \u2265\u00a03 (5% vs. 21% <jats:italic>P<\/jats:italic>\u00a0=\u00a00.25), and febrile neutropenia (5% vs. 16% <jats:italic>P<\/jats:italic>\u00a0=\u00a00.50) during PCR vs. normal diet. In conclusion, plasma SN\u201038 exposure increased dramatically after PCR, whereas toxicity did not change. PCR did not alter the irinotecan and SN\u201038 exposure in healthy liver and liver metastases. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan.<\/jats:p>","DOI":"10.1002\/cpt.2094","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T19:16:16Z","timestamp":1603998976000},"page":"1304-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients"],"prefix":"10.1111","volume":"109","author":[{"given":"Femke M.","family":"de Man","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben A.G.","family":"van Eerden","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerdien M.","family":"van Doorn","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Oomen\u2010de Hoop","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn L.W.","family":"Koolen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"},{"name":"Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne F.","family":"Olieman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"de Bruijn","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris N.","family":"Veraart","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk K.","family":"van Halteren","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Admiraal de Ruyter Hospital Goes The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yorick","family":"Sandberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Maasstad Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan","family":"Moelker","sequence":"additional","affiliation":[{"name":"Department of Radiology Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan N.M.","family":"IJzermans","sequence":"additional","affiliation":[{"name":"Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn P.","family":"Lolkema","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun","family":"van Gelder","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn E.T.","family":"Doll\u00e9","sequence":"additional","affiliation":[{"name":"Centre for Health Protection Research National Institute for Public Health and Environment (RIVM) Bilthoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron W.F.","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Department of Surgery Erasmus MC University Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ron H.J.","family":"Mathijssen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,6]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0644-7"},{"key":"e_1_2_10_2_1","first-page":"2182","article-title":"Clinical pharmacokinetics and metabolism of irinotecan (CPT\u201011)","volume":"7","author":"Mathijssen R.H.","year":"2001","journal-title":"Clin. 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