The dissertation on which the article is based was written two years ago by Judith Sáinz-Pardo under the direction of Professors Luis Alberto Fernández and Cecilia Pola de MATESCO, and justifies, with a mathematical approach, the superiority of metronomic chemotherapy
17 June 2022
The researcher from the Advanced Computing and e-Science Group at IFCA (CSIC-UC), Judith Sáinz-Pardo, together with a team of two researchers from the Department of Mathematics, Statistics and Computer Science (MATESCO) at the University of Cantabria (UC), have published an article in the prestigious journal 'Mathematical Modelling of Natural Phenomena', in which they justify, with a mathematical approach, the superiority of metronomic chemotherapy, which administers small doses on a regular basis, as opposed to the classical model, which advocates administering the maximum dose of drug tolerated in the treatment of cancer.
The origin of this article is the Final Degree Project of Judith Sáinz-Pardo, then a final year student in Mathematics, directed by MATESCO professors Luis Alberto Fernández and Cecilia Pola.
As professors Fernández and Pola explained, the design of more effective and less toxic chemotherapy treatments is a very active area of research in oncology. The classic chemotherapy approach "consists of administering the maximum tolerated dose of the drug. Its major drawback is the serious side effects it causes, often forcing the imposition of rest periods between cycles".
In 2000, metronomic chemotherapy was introduced, "which proposes a radically different approach: administering low doses of drugs frequently and regularly, which causes milder side effects, without compromising the outcome of the treatment. The efficacy of metronomic chemotherapy is often explained biologically by its 'anti-angiogenic' effect (i.e. its ability to stop the growth of new blood vessels that tumours need to grow). Also because it can activate anti-tumour immunity and minimise therapeutic resistance," they added.
From left to right: Luis Alberto Fernández, Cecilia Pola and Judith Sáinz-Pardo, in a computer room at the Faculty of Science. /UC
For her part, Sáinz-Pardo, a researcher at the IFCA, emphasised that the publication of this article "came about naturally after completing my dissertation in Mathematics. I presented it in July 2020, so it is very gratifying to see that now, two years later, it has been published in such a high-impact mathematical journal". The article has been published in a special volume on 'Cancer modelling' in 'Mathematical Modelling of Natural Phenomena', which is ranked sixth by impact factor (out of 265) in the Journal Citation Reports ranking, in the category 'Applied Mathematics'.
Classical versus metronomic chemotherapy
From the outset, the 'classical versus metronomic chemotherapy' debate has been (and continues to be) intense: in short, it is a matter of clarifying whether it is better to administer few high doses or many low doses. The aim is to elucidate for which cancers and drugs one approach or the other may be more appropriate. Experimentally, this question has been addressed through clinical trials, comparing the results of both types of treatment using statistical techniques. This approach is costly and not always very conclusive because of the number of factors involved and possible variants.
The research team commenting on a metronomic chemotherapy plot. / UC
There is an alternative approach in many branches of medicine that uses well-established mathematical models. This approach has been followed in the article "and has made it possible to mathematically justify that metronomic chemotherapy is the optimal strategy in oncology for many cytotoxic drugs (for both curative and palliative treatments), even without taking into account the additional benefits cited above," according to the MATESCO researchers.
In particular, this analysis has been performed for drugs with a short half-life (i.e. those that are eliminated by the body within a few hours at most), as well as for drugs with a long half-life, when their doses are administered at sufficiently spaced times. These theoretical conclusions bring a different and complementary perspective to the open debate on the subject and may help to clarify the situation hinted at by the experimental evidence, pointing to metronomic chemotherapy as the preferred medical treatment in these cases.
Luis A. Fernández, Cecilia Pola and Judith Sáinz-Pardo: "A mathematical justification for metronomic chemotherapy in oncology", Math. Model. Nat. Phenom. 17 (2022) 12 https://doi.org/10.1051/mmnp/2022010