Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 3

4463 - Effects of dietary restriction in cancer patients receiving irinotecan

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Ruben Van Eerden

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

R.A.G. Van Eerden1, F.M. de Man2, G.M. van Doorn3, E. Oomen-de Hoop4, S.L. Koolen5, J.F. Olieman3, P. de Bruijn1, J.N. Veraart1, H.K. van Halteren6, Y. Sandberg7, A. Moelker8, J.N.M. IJzermans9, M.P. Lolkema4, T. van Gelder10, M.E.T. Dollé11, R.W.F. de Bruin9, R.H.J. Mathijssen4

Author affiliations

  • 1 Medical Oncology Department, Erasmus MC Cancer Institute, 3015 GD - Rotterdam/NL
  • 2 Medical Oncology Dept, Erasmus University Medical Center, 3015 CE - Rotterdam/NL
  • 3 Department Of Dietetics, Erasmus University Medical Center, 3015GD - Rotterdam/NL
  • 4 Medical Oncology, Erasmus MC Cancer Institute, 3015 GD - Rotterdam/NL
  • 5 Medical Oncology And Hospital Pharmacy, Erasmus University Medical Center, 3015 GD - Rotterdam/NL
  • 6 Medical Oncology, Adrz-Admiraal de Ruijter Hospital-Goes, 4462RA - Goes/NL
  • 7 Medical Oncology And Hematology, Maasstad Ziekenhuis, 3079 DZ - Rotterdam/NL
  • 8 Department Of Radiology, Erasmus University Medical Center, 3015 GD - Rotterdam/NL
  • 9 Department Of Surgery, Erasmus University Medical Center, 3015GD - Rotterdam/NL
  • 10 Hospital Pharmacy, Erasmus MC Cancer Institute, 3015 GD - Rotterdam/NL
  • 11 8. center For Health Protection, National Institute of Public Health and Environment (RIVM), 3721 MA - Bilthoven/NL

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 4463

Background

Irinotecan is widely used, but also known for its severe toxicities neutropenia and diarrhea. Based on preclinical data, combined caloric and protein restriction (CCPR) might improve treatment tolerability without impairing antitumor effect. Therefore, we studied the influence of CCPR on irinotecan pharmacokinetics and toxicity.

Methods

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 CCPR (∼30% caloric and ∼70% protein restriction) during the 1st cycle and a 2nd cycle preceded by a normal diet (ND) or vice versa. During both cycles, 24-hours blood sampling was performed and 24-26 hours after infusion biopsies of both healthy liver (HL) and liver metastasis (LM) were taken. Primary endpoint was the relative difference in geometric means for the active metabolite SN-38 concentration in HL, as analyzed by a linear mixed model. Secondary endpoints included irinotecan and SN-38 concentrations in LM, plasma area under the curve (AUC0-24h), and toxicity.

Results

Interpatient variability (n = 19) in tissue irinotecan and SN-38 concentrations was high, showing no significant differences in irinotecan (+16.8%, 95% CI: -9.7-51.1%, P = 0.227) and SN-38 (+9.8%, 95% CI: -16.4-44.2%, P = 0.48) concentrations between CCPR and ND in HL, as well as in LM (irinotecan: -38.8%, 90% CI: -59.3:-7.9%, P = 0.05 and SN-38: -13.8%, 90% CI:-40.7-25.4%, P = 0.50). CCPR increased irinotecan plasma AUC0-24h with 7.1% (95% CI: 0.3-14.5%, P = 0.04) compared to ND, while the SN-38 plasma AUC0-24h increased with 50.3% (95% CI: 34.6-67.9%, P < 0.001). CCPR was well tolerated with low incidence of grade ≥3 therapy related toxicity. Grade ≥3 toxicity was not increased during CCPR 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), febrile neutropenia (5% vs 16% P = 0.50) and hospitalization (11% vs 21% P = 0.634) during CCPR vs ND.

Conclusions

CCPR resulted in a dramatically increased plasma SN-38 exposure, while toxicity did not change. CCPR did not result in altered irinotecan and SN-38 exposure in HL and LM. CCPR might therefore potentially improve the therapeutic window in patients treated with irinotecan.

Clinical trial identification

Netherlands Trial Register NL5624 (NTR5731) release date: 2016-03-04.

Editorial acknowledgement

Legal entity responsible for the study

A.H.J. Mathijssen.

Funding

Has not received any funding.

Disclosure

S.L. Koolen: Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Pfizer; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Cristal Therapeutics; Travel / Accommodation / Expenses: Ipsen. R.H.J. Mathijssen: Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi; Honoraria (institution): Servier; Honoraria (institution): Novartis; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Astellas. All other authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.