The Potential Role of Exercise on the
Bioavailability of Cancer Treatments
Maxime Caru1,2,3 and Daniel Curnier*1,2
1Faculty of Medicine, Laboratory of Pathophysiology of EXercise (LPEX), School of Kinesiology and Physical Activity Sciences, University of Montreal, Canada
2CHU Ste-Justine Research Center, CHU Ste-Justine, Canada
3Laboratoire EA 4430 - Clinique Psychanalyse Developpement (CliPsyD), University Paris Nanterre, France
Submission: March 21, 2019; Published: April 12, 2019
*Corresponding author: Daniel Curnier, Laboratoire de Physiopathologie de l’EXercice (LPEX), Département de Kinésiologie, Université de Montréal, CEPSUM, 2100, boulevard Édouard Montpetit, Montréal, QC H3C 3J7, Canada
How to cite this article: Maxime C, Daniel C. The Potential Role of Exercise on the Bioavailability of Cancer Treatments. Acad J Ped Neonatol.
2019; 7(4): 555775. DOI: 10.19080/AJPN.2019.07.555775
Recently, exercise in oncology has been proposed as an effective strategy in managing symptoms, reducing psychological distress (i.e. anxiety, depression) and easing the harmful effects of treatments. The studies showing the direct benefits of exercise on cancer are valuable. However, the mechanisms leading to these improvements are still unclear. The practice of exercise may influence the pharmacokinetics of drugs, but the number of studies in this field is limited. It then seems legitimate to hypothesize that exercise plays a role in the bioavailability of cancer drugs. As a matter of fact, no articles have focused on the role of exercise in the bioavailability of cancer drugs. This article shows a poverty of data examining the role of exercise in the bioavailability of cancer drugs. To our knowledge, this is the first published article to examine this issue.
Cancer is a complex disease characterized by the uncontrolled growth of abnormal cells. This disease is considered to be one of the leading causes of death in the world, with about 8.2 million deaths and 13% of overall mortality . In America, the improvement of clinical care over the past few decades has allowed improving the 5-year relative survival to 69% ; this being similar in other continents such as Europe . Some patients with cancer are sometimes obligated to rest excessively, which causes a lack of daily exercise resulting in a decrease in their functional state . Indeed, almost 68% of cancer patients do not comply with exercise recommendations, while this practice is safe for them . However, the literature is explicit about this as it informs that changes in the lifestyle, including exercise, can have a major impact on the risk of different types of cancer . Recently, exercise in oncology has been proposed as an effective strategy in managing symptoms, reducing psychological distress (i.e. anxiety, depression) and easing the harmful effects of treatments [7-9]. The studies showing the direct benefits of exercise on cancer are valuable . However, the mechanisms leading to these improvements are still unclear.
In oncology, the main cancer treatments are surgery, radiation therapy, and systemic therapy or chemotherapy . Most
anticancer therapies are administered intravenously rather than orally due to the immediate and complete bioavailability following intravenous administration . Oral drugs are attractive because of their convenience and ease of administration, but their solubility affects their bioavailability. Indeed, if a drug reports poor solubility, the absorption of the drug in the aqueous gastrointestinal fluids is insufficient . Several anticancer oral drugs have a low therapeutic window and the prescribed dose is close to the maximum dose tolerated by patients . The more effective the bioavailability of a drug, the better the delivery of the drug to the active site, optimizing pharmacokinetics. Pharmacokinetics explain the relationship between the absorption, distribution, metabolism, and excretion of a drug and its metabolites. Organisms respond only to the fraction which is biologically available . Thus, one of the current problems concerns the biological availability of oral anticancer drugs which have a low bioavailability . The practice of exercise may influence the pharmacokinetics of drugs, but the number of studies in this field is limited . It then seems legitimate to hypothesize that exercise plays a role in the bioavailability of cancer drugs. One of the plausible mechanisms for explaining this is that exercise would improves tissue and cell vascularization to optimize the transport of the cancer drug in the body. Some studies have investigated this mechanism in the murine model [17-19], however, to our knowledge, it does
not appear that there have been such studies in cancer patients.
As a matter of fact, no articles have focused on the role of
exercise in the bioavailability of cancer drugs. Our first aim is to
evaluate the effect of the exercise on the biological availability
of cancer drugs. The second aim is to show a poverty of data
examining the role of exercise in the bioavailability of cancer
drugs by a comprehensive review of the existing literature.
was performed by two independent reviewers (MC, DC) in
PubMed (MEDLINE) (1946 to January 30, 2019), Web of Science
(all databases) (1945 to January 30, 2019), EMBASE (1974 to
January 30, 2019), Cochrane Central Register of Controlled Trials
(November, 2016 to January 30, 2019), Reviews - Cochrane
Database of Systematic Reviews (2005 to January 25, 2019) and
Scopus (1970 to January 30, 2019). The search terms for inclusion
criteria are a combination of database specific MeSH terms and
keywords: “Motor Activity” OR exercise OR “physical activity”
OR sport* AND “Biological Availability” OR bioavailabilit* OR
“biological availability” AND “Neoplasms” OR cancer* OR tumor*.
When it is possible, in the different database, we add the human
filter. Also, the reference lists of all identified studies are scanned
manually for additional studies.
We included all studies which investigate exercise and the
biological availability of cancer drugs in human subjects without
any age restriction (age of children “≤” 18 and age of adults >19).
No publication date or language restrictions are applied to the
initial search. However, during the first analysis by abstract, the
conference abstracts, case reports, reviews, theses, letter to editor
or protocol paper are excluded due to the inability to evaluate the
risk of bias of the individual study. When the title and the abstract
are potentially eligible for inclusion, a full-text is obtained after
removal of duplicates. The studies with a design of randomized
controlled trials (RCT), nonrandomized controlled trials (NCT)
and uncontrolled interventions (i.e. pre and posttests without
controls) are included.
Two independent researchers (MC and DC) review the articles
for eligibility and validity. Data extraction is performed by one
investigator (MC); when data are lacking in the original article,
the authors of the review contact the original author to obtain
additional data. To assess scientific evidence for each study, this
review is conducted following the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses (PRISMA) statement .
A flow-chart showing the different phases of the review
according to the PRISMA schema is depicted in Figure 1. The
electronic database search generated 236 potential articles that
are screened for eligibility. After the first analysis by title and
abstract, 10 abstracts are assessed. Among these abstracts, 8 do
not meet our inclusion and exclusion criteria. A total of 2 studies
are identifed as eligible and valid for a full-text review. These 2
articles do not fit our criteria and are excluded.
The aim of this research is to examine the potential role of
exercise in the bioavailability of cancer drugs. Our study shows a
poverty of data examining the role of exercise in the bioavailability
of cancer drugs. To our knowledge, this is the first published
article to examine this issue.
The interaction of exercise and the bioavailability of cancer
drugs is legitimate. Indeed, exercise produces many positive
physiological changes in the human body. It is shown that exercise
increases muscular blood flow  and is positively correlated
with the increased content of red blood cells . In exercise
physiology, the main role of red blood cells is the transport of
oxygen by hemoglobin . However, in the human organism, the
red blood cells can also have a role in the transport of drugs .
In cancer patients, many suffer from anemia, since, they do not
have enough healthy red blood cells in their organism . This
is accentuated by chemotherapy treatments . Thus, in cancer,
the involvement of exercise in the transport of drugs is very
interesting. Indeed, exercise promotes the increase of red cell mass
and plasma blood allowing the increase of blood volume . The
implication of exercise in the transport of red blood cells in cancer
drugs is very important. Especially since the cellular absorption
of cytotoxic drugs (i.e. chemotherapeutics) is recognized in the
destruction of tumors .
This study shows that there is a significant lack of data on the
bioavailability of cancer drugs in exercise. The diagnosis and the
stage of cancer are two important characteristics that play in role
in how the body responds to bioavailability . Also, individual
characteristics and type of exercises practiced also play a role in
the response of the human body . The literature observes a
possible effect of exercise in improving the bioavailability of drugs.
The authors of this article hypothesize that exercise could promote
the bioavailability of cancer drugs through better vascularization
of the cancer cell, thus allowing greater circulation of red blood
cells carrying the cancer drugs. Further oncology studies are
required to better understand how exercise can have a potential
role in bioavailability of cancer drugs.