Open Menu
Meetings & Education
Meetings & Education
Research & Data
Practice & Patients
Career Development
News & Initiatives
Get Involved
A phase II randomized placebo-controlled study of fisetin and exercise to mitigate chemotherapy-related functional decline in postmenopausal women with early breast cancer (PROFFi).
Background: Despite substantial improvements in survival, postmenopausal survivors of breast cancer remain at high risk of functional decline after cancer treatment. One potentially targetable mechanism of chemotherapy-related functional decline is cellular senescence, a state of cell cycle arrest. Senescent cells (Sncs) develop a senescence-associated secretory phenotype (SASP), where they secrete a milieu of inflammatory cytokines that drive functional decline over time. In patients with stage I-III breast cancer treated with chemotherapy, markers of Sncs and SASP sharply increase after treatment and persist over time. Emerging data suggest that senolytics and exercise can decrease Snc burden. Senolytics are novel agents that eliminate Sncs and improve physical function in non-cancer populations. Among the existing senolytics, fisetin is a natural compound that is safe and tolerable in humans. Exercise also reduces Sncs in individuals without cancer and is well-established to improve physical function in survivors of cancer. More recent pre-clinical data shows that senolytics combined with exercise led to a greater reduction in Sncs than either intervention alone. However, no studies have tested whether senolytics and exercise, either alone or in combination, can reduce Sncs and improve physical function in cancer survivors. Therefore, we hypothesize that targeting Sncs with a combination of fisetin and exercise will lead to both independent and synergistic effects to prevent physical function decline in postmenopausal breast cancer survivors.
Methods: This multicenter phase II randomized, placebo-controlled study will enroll 200 postmenopausal women with stage I-III breast cancer. Key eligibility criteria include completing neo/adjuvant chemotherapy within 12 months with diminished physical function as measured by the 6-minute walk distance (6MWD). Using a 2x2 factorial design, participants will be randomized 1:1:1:1 to exercise with fisetin, exercise alone, fisetin alone, or a control group for a total 16-week course. Fisetin will be dosed at 20mg/kg on days 1-3 every 14 days. Those randomized to the exercise arms will undergo a tailored, supervised remote exercise program led by a qualified exercise physiologist. The primary objective is to determine the effect of fisetin and/or exercise on physical function, as measured by the change in 6MWD from baseline to end of treatment. Secondary objectives include evaluating the effect of exercise and/or fisetin on other measures of physical, cognitive, psychosocial, and cardiometabolic function as well as digital biomarkers. We will also examine the effect of exercise and/or fisetin on markers of Sncs and SASP. Enrollment on this study began July 2024 and is currently ongoing (NCT06113016).
Disclaimer
This material on this page is ©2025 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Author Details
Jingran Ji
UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, CA
Authors chevron_right
Associated Organizations chevron_right
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Symptom Science and Palliative Care
Track
Symptom Science and Palliative Care
View MoreAbstract Disclosure
open_in_new
Similar Abstracts
text_snippet
Abstract
2022 ASCO Annual Meeting
First Author: Jingran Ji
text_snippet
Abstract
2022 ASCO Annual Meeting
First Author: Tara B. Sanft
text_snippet
Abstract
2024 ASCO Annual Meeting
Effects of a pilot 12-week exercise program on breast cancer survivors’ quality of life.
First Author: Lauren Imai
text_snippet
Abstract
2024 ASCO Quality Care Symposium
First Author: Erin Aiello Bowles
Download
Your Privacy
ASCO is committed to transparency regarding our websites and the ways we process data. When you visit our site, we may store or retrieve information on your browser, mostly in the form of cookies. This information might be about you, your preferences, your location, or your device and is mostly used to make the site work as you expect it to and to personalize your web experience with us.
Because we respect your right to privacy, you can choose not to allow some or all types of cookies. Click on the different category headings to find out more about the types of cookies used on our websites and change your default settings to match your preferences. Please read these carefully. Blocking some types of cookies may impact your experience on the site, including our ability to personalize the content you receive from us.
For a full explanation of the personal and non-personal information we collect on our site, including how we use that information and your rights regarding that information, please review our Privacy Policy. Use of our website is also subject to our Terms of Use.
Allow All
Manage Consent Preferences
Essential Website Cookies
Always Active
These cookies are necessary for the website to function and are sometimes referred to as “strictly necessary” cookies. They make sure the website delivers you information and services in an optimal way.
They are often set in response to an action you take, such as changing your cookie preferences, setting your privacy preferences, logging in to our website, asking the site to remember you on subsequent pages, or filling in forms. These cookies do not identify you personally.
You can set your browser to block or alert you about all cookies, including essential website cookies, but some parts of the site will not work as a result.
Cookies Details‎
Performance and Functionality Cookies
Performance and Functionality Cookies
These cookies enhance the performance and functionality of our websites and the services we provide. For example, these cookies can keep track of your visitor session in between visits, enable you to share content through social media, use embedded media players, and use comment features. They also help us balance website load and improve site speed and performance.
All information these cookies collect is aggregated and therefore anonymous. These cookies may be set by us or by third party providers whose services we have added to our websites. These cookies are non-essential, but without these cookies, certain functionality or enhanced features may become unavailable.
Cookies Details‎
Personalization and Analytics Cookies
Personalization and Analytics Cookies
These cookies collect information that is used to help us understand how our websites and content are used, help us customize our websites and application for you in order to enhance your experience, and help us improve the content that ASCO creates to better meet our members’ and visitors’ needs. Examples include cookies that show us which content might be most popular with our visitors, understand browsing history of our users, understand the effectiveness of our own advertising, and enable us to recommend content to individual users based on their profile and activities on the website.
These cookies may be set by us or by third party providers whose services we have added to our websites.
These cookies are non-essential to the functionality of the site and may contain information that enables us or our third party providers to identify you and build a profile of your interests. Without these cookies, you will not be able to have a customized or personalized experience within our website.
Cookies Details‎
Advertising Cookies and Social Media Cookies
Advertising Cookies and Social Media Cookies
Advertising (or Targeting) cookies are third party cookies that may be set through our site by our advertising partners. They may be used by those companies to build a profile of your interests and show you relevant ads on other sites.
Social Media Cookies are cookies set by a range of social media services that we have added to the site to enable you to share our content with your friends and networks. They are capable of tracking your activities across other sites and building a profile of your interests. This may impact the content and messages you see on other websites you visit.
These cookies and the data collected by the third parties may be combined with data from other users or data about your activity on other sites. While the data collected on our site is aggregate or non-personal, the data may be used by such third parties to link you on other platforms or otherwise identify you.
If you do not allow these cookies, you may experience less targeted advertising.
Cookies Details‎
Back Button
Cookie List
Search Icon
Filter Icon
Clear
checkbox labellabel
ApplyCancel
ConsentLeg.Interest
checkbox labellabel
checkbox labellabel
checkbox labellabel
View Cookies
Name
cookie name
Save Settings
