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IBSA Foundation_Dosaggio chemioterapia con algoritmo
Paolo Rossi Castelli23 May 20243 min read

Chemotherapy: the right amount of the drug is decided by an algorithm in real time

A new method of administering chemotherapy has been developed by MIT in Boston, outperforming the somewhat dated current system based on the “empirical” calculation of body surface area.Thanks to the new device, known as CLAUDIA, blood is taken every five minutes, and the “machine” adjusts the dosage in real time to the most effective level.

The chemotherapy drug dosage (the quantity of the drug to be administered to cancer patients) to be given intravenously is currently based on the calculation of the body surface area, a parameter that takes into account weight and height, initially developed in 1916 after an assessment carried out on a small number of cancer patients, and then gradually updated.

Although more accurate than the dosages of other types of drugs, today this system is showing its age and all its inadequacies. In fact, it is possible that two people with the same body surface area can be very different (for example, one can be tall and thin, and the other short and overweight, with different amounts of muscle mass and other tissue mass). Furthermore, patients can have a different microbiota, a factor that significantly affects the reaction to treatment (as shown by recent studies). Also, patients may be taking other drugs which, in turn, affect the metabolism of anticancer drugs. Or patients may have genetic differences that could strengthen or weaken the action of certain enzymes involved in the “management” of the drugs. Finally, the intake of chemotherapy drugs at different times of day could have an effect, because the expression of some of the enzymes that metabolise them could change.

Chemotherapy administration: effectiveness and toxicity

All the variables described above, together with others, have an impact on two fundamental aspects: the effectiveness and toxicity of the chemotherapy, which are considered to be in the normal range when the concentration of drugs stays within the therapeutic range. However, precisely because of the variables mentioned, in many cases this only occurs during part of the chemotherapy administration. The rest of the time, the drugs are often too concentrated (and therefore put the patients at risk of excessive toxicity, which could be avoided), or too diluted - with the risk, in this case, that the patients do not get the full benefit that they could otherwise have.

Promising initial results

To overcome the inaccurate body surface area criterion, bioengineers at the Massachusetts Institute of Technology (MIT) have developed a system that has produced very promising results in laboratory animals.
The drug used for the trials was one of the oldest and trickiest chemotherapies to administer (still in circulation): 5-fluorouracil or 5FU, which is administered by infusions that can last up to 46 hours. As reported in the scientific journal Med, the idea was to continuously monitor the 5FU blood concentration and to immediately transfer this monitoring data to the system that dispenses the drug, adjusting the dose each time so that it stays as long as possible in the therapeutic range.

Measurements every 5 minutes

The system, known as CLAUDIA (Closed-Loop AUtomated Drug Infusion regulAtor), takes a blood sample using a special needle every 5 minutes, and immediately doses the chemotherapy (in this case 5FU) using a chromatograph (an instrument that separates the components of a liquid or gaseous mixture). It then sends the data to an algorithm, which adjusts the release of the drug based on the information received.

In the laboratory animals monitored by the CLAUDIA device, the 5FU remained within the therapeutic range (the range between the dose necessary to have the desired pharmacological effect and the dose that gives rise to a toxic effect) for 45% of the time, while in the controls (not “measured” using the new device), this happened for only 13% of the time. The potential is therefore clear.

Researchers have, for now, developed an experimental CLAUDIA device, but encouraged by the positive results of the first trials they are looking to develop a device that can be standardised and mass produced - following new tests - so that is can also be used on humans, with notable benefits, at least potentially, for patients.


 

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Paolo Rossi Castelli

Journalist since 1983, Paolo has been dealing with scientific divulgation for years, especially in the fields of medicine and biology. He is the creator of Sportello Cancro, the site created by corriere.it on oncology in collaboration with the Umberto Veronesi Foundation. He collaborated with the pages of the Science of Corriere della Sera for several years. He is the founder and director of PRC-Comunicare la scienza.

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