Timing of Therapy
Some physicians and scientists suggest that administering chemotherapy, immunotherapy, or radiotherapy at a specific time of day can improve response to treatment.
Timing of therapy at a glance
Chronomodulated therapy (from chronos, or time) refers to administering cancer therapy at a certain time of day.
Both cancerous and healthy tissues are influenced by the body’s internal 24-hour clock. Cell growth is not constant: cells cycle between periods of replication and dormancy over the course of the day. Cells of every type are most vulnerable to damage from chemotherapy, radiation, and many targeted drugs when they are actively dividing, and are less vulnerable when they are in a resting phase. Chronomodulated therapy takes advantage of this by delivering treatment at hours when cancer cells are more likely to be proliferating, while surrounding normal tissues, such as the gastrointestinal lining and bone marrow, are not proliferating. By adjusting the timing of treatment, oncologists aim to increase the anticancer effect while reducing side effects.1Rich TA, Shelton CH et al. Chronomodulated chemotherapy and irradiation: an idea whose time has come? Chronobiology International. 7 July 2009. 19(1): 191-205.
In some cases, chronomodulation can also refer to changing the length and concentration of treatment: for example, administering a chemotherapy infusion over 24 hours, instead of one hour. This type of chronomodulation has been in use in oncology for many years.
The current evidence shows that administering immunotherapy earlier in the day may benefit survival, although the effect is small and variable.2Landré T, Karaboué A et al. Effect of immunotherapy-infusion time of day on survival of patients with advanced cancers: a study-level meta-analysis. ESMO Open. 2024 Feb;9(2):102220; Qian DC, Kleber T et al. Effect of immunotherapy time-of-day infusion on overall survival among patients with advanced melanoma in the USA (MEMOIR): a propensity score-matched analysis of a single-centre, longitudinal study. Lancet Oncology. 2021 Dec;22(12):1777-1786; Rizzo A, Monteiro FSM et al. Impact of time-of-day administration of immunotherapy on survival in metastatic renal cell carcinoma: the MOUSEION-09 meta-analysis. Clinical and Experimental Metastasis. 2024 Dec 16;42(1):3. Chrono-chemotherapy studies are few, and have produced limited results. Furthermore, at least one study showed sex differences: female patients with metastatic colorectal cancer fared poorly when chemotherapy was given in a chronomodulated format, while in contrast, male patients survived longer with the same chronomodulated administration schedule.3Giacchetti 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.
While small studies suggested that morning radiotherapy for brain metastases might benefit survival,4Chan S, Rowbottom L et al. Does the time of radiotherapy affect treatment outcomes? A review of the literature. Clinical Oncology (Royal College of Radiologists). 2017 Apr;29(4):231-238. more detailed analyses have not found this effect.5Badiyan SN, Ferraro DJ et al. Impact of time of day on outcomes after stereotactic radiosurgery for non-small cell lung cancer brain metastases. Cancer. 2013 Oct 1;119(19):3563-9. Finally, while some studies show that people receiving certain chemotherapy drugs for colon cancer had fewer side effects on a chronomodulated schedule, they did not show a better treatment response.
While studies so far have found a minimal effect on survival, chronomodulation may be useful in reducing side effects, which in turn may help patients stay on treatment longer and enjoy a better quality of life. Several studies show that chronomodulated FOLFOX chemotherapy for colorectal cancer decreases side effects.6Huang Y, Yu Q et al. Efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer: a systematic review and meta-analysis. Asia Pacific Journal of Clinical Oncology. 2017 Apr;13(2):e171-e178.
The evidence for timed radiation therapy is scant but noteworthy: morning radiation treatments decrease side effects in patients with head and neck cancer,7Abusamak M, Abu-Samak AA et al. Chronotherapy in head and neck cancer: A systematic review and meta-analysis. International Journal of Cancer. 2025 Mar 1;156(5):1015-1032. while evening radiation has in one study been associated with increased gastrointestinal distress in patients with prostate cancer.8Hsu 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.
Overall, chronotherapy remains an intriguing but underdeveloped field. For most chronomodulated treatment schedules, a lack of research leaves us in the dark about whether such schedules help patients. In addition, most of the available evidence was generated more than a decade ago. In the interim, cancer drugs and standard treatment guidelines have changed, making those older studies harder to interpret in today’s context.
CancerChoices ratings for timing of therapy
We rate timing of therapy on six attributes, with 0 the lowest rating and 5 the highest. We rate the strength of the evidence supporting the use of timing of therapy for a medical benefit, such as improving treatment outcomes or managing side effects.
See how we evaluate and rate complementary therapies ›
Improving treatment outcomes
See More- Immunotherapy:
- People with cancer receiving immunotherapy earlier in the day showed longer overall survival across several studies.
- People with metastatic renal cell carcinoma receiving immunotherapy earlier in the day showed better overall survival across several studies.
- People with melanoma receiving 20% or more of their immunotherapy infusion sessions after 4:30 p.m. showed lower overall survival in one observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study.
- Chemotherapy:
- People with head and neck cancer receiving platinum-based and antimetabolite chemotherapy in the morning, compared to the evening, showed a higher rate of good response to chemotherapy across several studies.
- People with early breast cancer who received endocrine therapy in the evening or at night using tamoxifen, but not aromatase inhibitors, showed longer disease-free survival in one study.
- Some evidence suggests a sex difference in response to chronomodulated chemotherapy for colorectal cancer (5-fluorouracil in the morning and oxaliplatin in the evening), with female patients showing shorter overall survival time but male patients showing longer overall survival time in one study.
- People undergoing chemotherapy and radiotherapy for nasopharyngeal carcinoma who received the chemotherapy on a specified 24-hour schedule (cisplatin during the day, 5-fluorouracil overnight) compared to standard schedule showed a better response at one month, but no evidence of an effect on survival at one year or longer from treatment.
- Radiation:
- People with stage 2b-3 prostate cancer receiving high-dose radiotherapy in the evening showed worse progression-free survival in one study.
Optimizing your body terrain
See MoreChronomodulated therapy has not been studied for any of the body terrain factors we look at.
Managing side effects and promoting wellness
See More- Blood-related side effects:
- People with metastatic colorectal cancer receiving chrono-chemotherapy (mostly receiving 5-fluorouracil in the morning and oxaliplatin in the afternoon) showed less neutropenia (an abnormally low number of neutrophils in the blood, which can increase susceptibility to infection) in a combined analysis of studies.
- People undergoing irinotecan chemotherapy for metastatic colorectal cancer showed a sex difference in neutropenia depending on timing of chemotherapy, with female patients showing less neutropenia when they received it in the afternoon but male patients showing less neutropenia when they received it in the morning, in one study.
- People with non-small-cell lung cancer receiving cisplatin chemotherapy with docetaxel or gemcitabine showed less neutropenia and leukopenia (an abnormally low number of white cells in the blood leading to increased susceptibility to infection) when the cisplatin was administered at 6 p.m. in one study.
- People undergoing chemotherapy and radiotherapy for nasopharyngeal carcinoma who received cisplatin during the day and 5-fluorouracil overnight showed less leukopenia and less thrombocytopenia (an abnormally low number of platelets in the blood, which may cause easy bruising and excessive bleeding from wounds or bleeding in mucous membranes and other tissues) in one study.
- People receiving vinorelbine chemotherapy (5-fluorouracil) for metastatic breast cancer 5 P.M. compared to other times of day showed less leukopenia but worse levels of other side effects in one study.
- People undergoing ifosfamide chemotherapy undergoing bone or soft tissue cancer who received granulocyte-macrophage colony-stimulating factor (GM-CSF) at night showed more neutropenia in one study.
- Changes in appetite:
- Female patients undergoing irinotecan chemotherapy for metastatic colorectal cancer in the afternoon, but male patients undergoing chemotherapy in the morning, showed better appetite in one study.
- Gastrointestinal side effects:
- People with prostate cancer receiving high-dose radiotherapy in the evening showed worse gastrointestinal side effects in one study.
- People receiving chrono-chemotherapy (mostly 5-fluorouracil in the morning and oxaliplatin in the afternoon) for metastatic colorectal cancer did not show evidence of an effect on severe nausea and vomiting across several studies.
- People receiving chemotherapy and radiotherapy for nasopharyngeal carcinoma on a specified 24-hour schedule (cisplatin during the day, 5-fluorouracil overnight) showed less nausea and vomiting in one study. People in another study receiving cisplatin chemotherapy for nasopharyngeal cancer on a 12-hour sinusoidal pump, with peak delivery at 4pm, also showed less nausea and vomiting.
- People with non-small-cell lung cancer receiving cisplatin chemotherapy with docetaxel or gemcitabine showed less nausea when the cisplatin was administered at 6 p.m. in one study.
- People with metastatic gastrointestinal cancer receiving 5-fluorouracil chemotherapy and leucovorin as intermittent (waxing and waning) infusions showed less diarrhea in one study. Meanwhile, people undergoing irinotecan chemotherapy for metastatic colorectal cancer showed evidence of a sex difference, with females having less diarrhea when receiving their infusions in the afternoon but males showing less diarrhea when receiving it in the morning, in one study.
- Neuropathy and neurologic symptoms:
- People with metastatic colorectal cancer receiving 5-fluorouracil and oxaliplatin chemotherapy with leucovorin on a waxing-and-waning schedule showed less impairment from neuropathy in one study.
- Oral symptoms (mucositis):
- People with head and neck cancer undergoing radiation in the morning rather than the evening showed less severe oral mucositis across several studies.
- People with metastatic colorectal cancer receiving chrono-chemotherapy (mostly 5-fluorouracil in the morning and oxaliplatin at night) showed less mucositis across several studies. So did people with metastatic gastrointestinal cancer receiving 5-fluorouracil chemotherapy and leucovorin as intermittent (waxing and waning) rather than flat infusions in two studies.
- People with nasopharyngeal carcinoma receiving cisplatin chemotherapy on a 12-hour sinusoidal pump, with peak delivery at 4pm, showed less mucositis in one study.
- People with non-small-cell lung cancer receiving 5-fluorouracil and carboplatin chemotherapy with 5-fluorouracil at 4 a.m. and carboplatin at 4 p.m. showed less mucositis in one study.
- Skin and tissue side effects:
- People with breast cancer who received radiation therapy in the morning had fewer skin reactions in one study.
- People with colorectal cancer undergoing 5-fluorouracil chemotherapy, with or without carboplatin, where the chemotherapy was administered more slowly (over 4 days compared to 2 days) showed more skin-related side effects in one study.
- Overall side effects:
- People with head and neck cancer undergoing chemotherapy in the morning, compared to the evening, showed fewer overall side effects and adverse events across several observational studies.
- People with ovarian cancer undergoing doxorubicin and cisplatin chemotherapy who received doxorubicin in the evening and cisplatin in the morning, compared to the other way round, showed more overall side effects in one study.
Reducing cancer risk
See More- Weak evidenceone or more case studies, supported by animal evidence OR small treatment effects of limited clinical significance OR studies with no controls OR weak trends of effects (this is the CancerChoices definition; other researchers and studies may define this differently) of less recurrence than usual among people with bladder cancer undergoing chemotherapy who received doxorubicin in the morning and cisplatin in the evening
Safety
See More- The safety of chronomodulation depends on the treatment regimen, your cancer type, and your own body terrain. While chronomodulation appears to be generally safe, certain timings of chemotherapy and radiotherapy can produce worse side effects.
- There may be a sex difference in response to certain chronomodulated schedules. In one study, female patients with metastatic colorectal cancer receiving chronomodulated chemotherapy showed shorter survival, while the same regimen increased survival among male patients.
Affordability and access
See More- Access depends on your treating physician or infusion center. Many patients have access to portable pumps, which can deliver chemotherapy at home on a schedule. However, it may be more difficult to adjust the timing of procedures like radiation.
Keep reading about timing of therapy
Author
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.
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.
Reviewer
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.
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.
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