Francis Levi, cancer (1), just to show that we can improve chemotherapy

Cross. You have just published an article (2) showing interest in patients with cancer receiving treatment, taking into account the biological clock of each individual. What is this therapy?
Francis Levi: We have shown that taking into account the biological clock of patients in the administration of drugs can reduce their toxicity on healthy cells. This is called chronotherapy. It aims to determine the ideal time to administer a drug during chemotherapy, taking into account the internal biological rhythms of the body: rectal temperature, rate of secretion of hormones, the rate of activity of detoxification enzymes liver…

What is the initial idea?
Today, most cancers are treated with chemotherapy alone or in combination with surgery or radiotherapy. Side effects of the chemotherapy are many and can sometimes lead to discontinuation of treatment due to a risk-benefit balance against. The chronotherapy is a solution to minimize these possible effects, or improve the effectiveness of treatment.

Has shown your last job?
Within the European project tempo, we tested the chronotoxicite two molecules, irinotecan, used for the treatment of colorectal cancer, and Seliciclib, under development. In humans, the adverse effects of irinotecan are manifested by severe diarrhea in 30% of patients, a decrease in white blood cells in almost half of cases and a state of extreme tiredness. As for Seliciclib, it can also cause severe fatigue and metabolic disorders. In mice, we administered these drugs at different periods of sleep-wake rhythm that lasts about twenty-four hours. Results: The harmfulness of these molecules varies at least from one to three depending on time of administration. Thus, it is likely that, in humans, irinotecan should be administered at about 5 o’clock in the morning and Seliciclib to 2 am. We have also shown that chronotoxicite depends on sex and genetic makeup of animals.

What this will change for patients?
Based on these results, we will adapt the treatment of patients with programmable pumps (chronopompes). Currently, a dozen cancer services in Europe, the chronopompe is set to profile chronobiological means. Now it will be based on chronobiological profile of each patient. This will enable personalized medicine and ambulatory treatment better tolerated psychologically. Furthermore, we are developing a thermometer implanted that will provide physicians the internal biological rhythm of each patient. This will fit even better treatment. Seven teams are European and testing from 2010 therapeutic methods based on these rhythms.

Collected by Denis Sergent

(1) Research Director at Inserm (Paul Brousse Hospital in Villejuif).
(2) Annual Review of Pharmacology and Toxicology.

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