Effects of Protein and Calorie Restriction on the Metabolism and Toxicity Profile of Irinotecan in Cancer Patients.

Autor: de Man FM; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Eerden RAG; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Doorn GM; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Oomen-de Hoop E; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Koolen SLW; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Olieman JF; Department of Internal Medicine, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., de Bruijn P; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Veraart JN; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Halteren HK; Department of Internal Medicine, Admiraal de Ruyter Hospital, Goes, The Netherlands., Sandberg Y; Department of Internal Medicine, Maasstad Hospital, Rotterdam, The Netherlands., Moelker A; Department of Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., IJzermans JNM; Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Lolkema MP; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Gelder T; Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Dollé MET; Centre for Health Protection Research, National Institute for Public Health and Environment (RIVM), Bilthoven, The Netherlands., de Bruin RWF; Department of Surgery, Erasmus MC, University Medical Center, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2021 May; Vol. 109 (5), pp. 1304-1313. Date of Electronic Publication: 2020 Dec 06.
DOI: 10.1002/cpt.2094
Abstrakt: 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 days of PCR (~ 30% caloric and ~ 70% protein restriction) during the first cycle and a second cycle preceded by a normal diet or vice versa. 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-38 concentration in healthy liver 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 normal diet in healthy liver, as well as in liver metastases (irinotecan: -38.8%, P = 0.05 and SN-38: -13.8%, P = 0.50). PCR increased irinotecan plasma area under the curve from zero to 24 hours (AUC 0-24h ) with 7.1% (P = 0.04) compared with normal diet, whereas the SN-38 plasma AUC 0-24h increased with 50.3% (P < 0.001). Grade ≥ 3 toxicity was not increased during PCR vs. normal diet (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. normal diet. In conclusion, plasma SN-38 exposure increased dramatically after PCR, whereas toxicity did not change. PCR did not alter the irinotecan and SN-38 exposure in healthy liver and liver metastases. PCR might therefore potentially improve the therapeutic window in patients treated with irinotecan.
(© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
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