Circadian rhythm-based cancer therapy in randomised clinical trials

ABSTRACT

Introduction

Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers.

Areas covered

The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov.

Expert opinion

Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment.

KEYWORDS:

• Circadian clock
• circadian rhythm
• chrono-oncology
• radiotherapy
• chemotherapy
• gender-medicine
• controlled clinical trial

Article highlights

• The biological clock/circadian rhythm is a factor impacting on treatment response.

• Chronotherapy is the treatment administered based on the biological clock.

• Studies support the role of chronotherapy in cancer patients through better healthy tissue protection.

• Previous and ongoing clinical trials suggest a role of chronotherapy in cancer management

• Implementation of chronotherapy into clinical routine is accessible and cost free.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.