Donate
Donate
icon
icon
Find help
Top questions Click or tap to explore common questions to get started ›
Request a volunteer guide Find someone to help you navigate this site ›
Find cancer-specific handbooks
Integrative Cancer Care Handbooks ›
Sign up for email updates
Sign up for e-news updates ›
Top questions

Some physicians and scientists suggest that administering chemotherapy, immunotherapy, or radiotherapy at a specific time of day can improve response to treatment.

Safety and precautions

While chronomodulated itself does not appear to have specific safety risks, patients in one study of a chronomodulated chemotherapy schedule showed a sex difference in survival, which may reflect underlying differences in circadian rhythms. Another study found that neutropenia on chronomodulated FOLFOX chemotherapy predicted worse outcomes, though chronomodulation itself did not appear to have an effect. 

Lower survival among female patients receiving chronomodulated colorectal cancer chemotherapy 

Female patients with colorectal cancer showed shorter overall survival time on a chronomodulated chemotherapy schedule that increased survival among male patients compared to non-time-specified infusions.1Giacchetti S, Dugué PA et al. Sex moderates circadian chemotherapy effects on survival of patients with metastatic colorectal cancer: a meta-analysis. Annals of Oncology. 2012 Dec;23(12):3110-3116.

Shorter progression-free survival among people with stage 2b-3 prostate cancer receiving high-dose radiotherapy in the evening compared to the daytime in one observational study.2Hsu FM, Hou WH et al. Differences in toxicity and outcome associated with circadian variations between patients undergoing daytime and evening radiotherapy for prostate adenocarcinoma. Chronobiology International. 2016;33(2):210-9.

Lower survival among those with worse neutropenia during chronomodulated FOLFOX chemotherapy

Shorter survival among people with metastatic colorectal cancer with less neutropenia from circadian-aligned FOLFOX chemotherapy, compared to longer survival among those with worse neutropenia from non-time-specified FOLFOX chemotherapy in a mid-sized RCT.3Innominato PF, Giacchetti S et al. Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963). Chronobiology International. 2011 Aug;28(7):586-600. Note: according to the authors, this result indicates that in chronotherapy, oncologists should not always choose the highest tolerated dose as indicated by neutropenia.

In the same study, people with metastatic colorectal cancer who had worse neutropenia from FOLFOX chronotherapy (5-fluorouracil in the morning and oxaliplatin in the evening) showed worse survival, but those with less neutropenia showed better survival.

Side effects or adverse events

People with colorectal cancer experienced more skin-related side effects in two studies investigating different chronomodulated chemotherapy regimens.4Focan C, Bury J et al. Chimiothérapie adjuvante pour le cancer du colon de stades Dukes B2 et C comportant du 5-fluorouracile et de l’acide folinique, avec ou sans carboplatine. Faisabilité et comparaison d’une administration standard à une administration chronomodulée [Adjuvant chemotherapy for Dukes B2 and C colon cancer combining 5-fluorouracil and folinic acid with or without carboplatin. Feasibility and comparison between standard and chronomodulated deliveries]. Pathologie-Biologie (Paris). 2005 Jun;53(5):281-4. French; Akgun Z, Saglam S et al. Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study. Cancer Chemotherapy and Pharmacology. 2014 Oct;74(4):751-6.

People with metastatic breast cancer treated with chronomodulated 5-fluorouracil chemotherapy at 5 p.m. compared to other times of day experienced less leukopenia but worse gastrointestinal side effects (nausea, diarrhea, and stomach pain) compared to other times of day.5Coudert B, Focan C et al. A randomized multicenter study of optimal circadian time of vinorelbine combined with chronomodulated 5-fluorouracil in pretreated metastatic breast cancer patients: EORTC trial 05971. Chronobiology International. 2008 Sep;25(5):680-96.

Keep reading about timing of therapy

Choose what to read next
See all our reviews of complementary therapies

Author

Sophie Kakarala

Research Assistant
View profile

Sophie received her Bachelor of Arts from the University of Cambridge, where she studied Middle Eastern languages and the philosophy of science. She then completed a premedical post-baccalaureate at the City University of New York. Before joining CancerChoices, she worked for several years at the Cornell Center for Research on End-of-Life Care, where she helped to conduct research on terminal illness and grief. Working in end-of-life research filled her with the conviction that all patients deserve free, accessible, and scientifically accurate information about the therapies available to them. While taking classes in anthropology, she also became curious about traditional medical knowledge and philosophies. These interests led her to CancerChoices. She is delighted to be part of CancerChoices’s work creating rigorous, evidence-based treatment guides for patients and physicians.

Sophie Kakarala Research Assistant

Nancy Hepp, MS

past Lead Researcher
View profile

Ms. Hepp is a researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. She serves as lead researcher and writer for CancerChoices and also served as the first program manager. Her graduate work in research and cognitive psychology, her master’s degree in instructional design, and her certificate in web design have all guided her in writing and presenting information for a wide variety of audiences and uses. Nancy’s service as faculty development coordinator in the Department of Family Medicine at Wright State University also provided experience in medical research, plus insights into medical education and medical care from the professional’s perspective.

Nancy Hepp, MS past Lead Researcher

Reviewer

Dawn Lemanne, MD, MPH

CancerChoices advisor
View profile

Founder of Oregon Integrative Oncology, Dr. Lemanne is a Stanford-trained and board-certified oncologist whose practice combines advanced conventional treatments with evidence-based complementary therapies. She seeks out the best conventional treatment, then employs personalized lifestyle interventions to enhance treatment efficacy and maximize survival after a cancer diagnosis. She is particularly involved in using genetic and metabolic parameters to personalize diet and exercise recommendations.

Dr. Lemanne attended UCSF School of Medicine and completed a three-year internal medicine residency at Henry Ford Hospital in inner-city Detroit. She completed a medical oncology fellowship at Stanford University. Dr. Lemanne holds advanced degrees in epidemiology from UC Berkeley and in science writing from Johns Hopkins University. Dr. Lemanne is also a graduate of the University of Arizona’s two-year integrative medicine fellowship. Following graduation she joined the faculty of Memorial Sloan Kettering Cancer Center. There she served as the first medical oncologist in the integrative medicine service.

Dr. Lemanne continues her association with the University of Arizona, developing much of the current oncology curriculum for UA’s Integrative Medicine Fellowship, including the popular courses “Breast Cancer” and “Nutrition and Cancer.” She lectures widely on integrative oncology, and has authored textbook chapters, peer-reviewed scientific papers, and works for the lay press, including the book “n of 1,” with coauthor Glenn Sabin.

Dawn Lemanne, MD, MPH CancerChoices advisor

Last update: January 25, 2026

Last full literature review: March 2025

CancerChoices provides information about integrative in cancer care, a patient-centered approach combining the best of conventional care, self care and evidence-informed complementary care in an integrated plan cancer care. We review complementaryin cancer care, complementary care involves the use of therapies intended to enhance or add to standard conventional treatments; examples include supplements, mind-body approaches such as yoga or psychosocial therapy, and acupuncture therapies and self-care lifestyle actions and behaviors that may impact cancer outcomes; examples include eating health-promoting foods, limiting alcohol, increasing physical activity, and managing stress practices to help patients and professionals explore and integrate the best combination of conventionalthe cancer care offered by conventionally trained physicians and most hospitals; examples are chemotherapy, surgery, and radiotherapy and complementary therapies and practices for each person.

Our staff have no financial conflicts of interest to declare. We receive no funds from any manufacturers or retailers gaining financial profit by promoting or discouraging therapies mentioned on this site.

Learn more

Making Skillful Decisions about Cancer Treatment

Healing

Blog and Stories

References[+]