DiaChemo

Revolutionising chemotherapy monitoring

The dose of chemotherapeutic drugs is calculated on the basis of the patient’s body surface area, without considering their metabolism, making it difficult to assess the concentration of the drugs in blood. Silke Krol, Ph.D tells us about the DiaChemo project’s work in developing a point-of-care device that will enable clinicians to monitor the concentration of drugs in blood during treatment.

The drug dose for a patient undergoing chemotherapy is typically calculated on the basis of their body surface area, without taking their metabolism into account. This approach has significant drawbacks which can limit the effectiveness of treatment, as Silke Krol, PhD explains. “A patient who is tall and thin is likely to have a completely different metabolism to someone who is small and fat, yet they may get the same drug dose. This means that one person is likely to receive a toxic dose while the other is perhaps underdosed, and so the tumour will not be treated effectively,” she points out. This is an issue Krol and her colleagues in the DiaChemo project are addressing by developing a pointof-care device to monitor the concentration of chemotherapy drugs in blood during the treatment. “Toxic concentrations are quickly visible in the patient. The higher risk is undertreating the patient, where the concentration of the drug in blood never reaches the level required to treat the tumour effectively,” she explains.

DiaChemo project This is central to the motivation behind the DiaChemo project, an EU-funded initiative which brings together partners from across Europe. The idea behind the project is to develop a hand-held device which is able to monitor and measure, within a maximum

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period of 30 minutes, the concentration of different chemotherapeutics in blood. “We are trying to measure the actual concentration of a drug in blood during treatment, in order to ensure that the concentration is always in the therapeutic window. So, this means higher than the lowest necessary concentration, and lower than the toxic

bound to nanoparticles, one for the drug itself, and others for the different metabolites. By measuring the concentration of the bound molecules on the different nanoparticles, researchers can then determine the ratio between the drugs and the metabolites. “This gives us an idea about the metabolism of the patient, and also the drug concentration,”

We are trying to measure the actual concentration of a drug in blood during cancer treatment, in order to guarantee that the concentration is always in the therapeutic window. So, this means higher than the lowest necessary concentration, and lower than the toxic concentration. concentration,” outlines Dr Krol. The device is based on a type of platform technology, a modular system. “The idea is to have a very simplified system, in which we will be able to measure concentrations of doxorubicin and irinotecan for example, two drugs commonly used in chemotherapy,” continues Dr Krol.

“These drugs have specific properties, like fluorescence or light absorption, which allow us to have a very simplified, cheap, easy and fast system for the read-outs.”

Another module of the device includes a type of extraction system, in which the drug molecules or their metabolites are selectively

outlines Dr Krol. The modular structure of the device means it can be used to measure the concentrations of different drugs in the same sample, an important point given that chemotherapy treatment often involves combinations of several drugs. “We are developing separate approaches for each drug, with nanoparticles which are selective for different drugs. By using a microfluidic read-out system, we are able to detect different drugs in the same blood sample in parallel,” explains Dr Krol.

A system developed to measure the concentration of an antibody will not be able

EU Research

to detect the concentration of irinotecan for example. However, with different modules in the device, Dr Krol says it will be possible to measure the concentration of irinotecan in the presence of the antibodies. “In one channel, we can have the detection system and read-out system for irinotecan and so determine the concentration, and in the next one we can determine the concentration of an antibody,” she says. Attention in the project has been focused on four different drugs commonly used in chemotherapy, yet the device could be applied to measure other drugs. “We aim to develop a kind of platform technology, so that we can measure the concentrations of different drugs in a very easy and timely manner,” says Dr Krol. “It’s extremely important to have a clear idea about the free drug concentration in the blood.”

This could allow clinicians to adjust the therapy to the needs of a particular patient, which will help improve outcomes and improve efficiency in healthcare systems. At the moment, somewhere between 30-60 percent of the drugs administered to patients don’t have the desired effects; Dr Krol says the DiaChemo device can help medical doctors to adapt the therapy to the individual patient. “With this device you will be able to identify, at a very early stage, those patients who cannot be treated with a specific drug, maybe because their metabolism is so fast that the toxic concentration is never reached.

In that case you can switch to another drug, which means reduced side-effects for the patient, and lower costs for the health system,” she outlines. “This system will allow

us to both optimise the outcome of therapy, reducing toxic effects on patients, and also to ensure that drugs are used more effectively.

With this system you can see very quickly if a patient is ‘treatable’ with a particular type of drug.”

Drug monitoring The potential applications of this device are not limited just to measuring concentrations of chemotherapeutic drugs, as this topic is of interest across many areas of medicine. While attention in the project has mainly been focused on developing a device to measure chemotherapeutic drugs, Dr Krol says their research also holds wider relevance. “We are aiming to develop a modular system and platform technologies. With some relatively minor modifications, such as developing different types of nanoparticles or adding other modules for more sophisticated measurements, we can adjust the whole system to measure other drugs, not just chemotherapeutic drugs,” she outlines. Two prototypes will be developed and validated by the clinical partners of the project, after which researchers will then look towards the application of the device. The clinical partners are presenting to the two endusers of the device – a hospital for cancer in children and a hospital treating adults – and Dr Krol says there is a lot of interest in the project’s work. “There is high demand for this type of device. I work in a hospital, and when I speak to medical doctors, the questions are always about the progress of development and when the device can be utilized by clinicians,” she stresses.

The DiaChemo team.

www.euresearcher.com

DiaChemo Point-of-care microfluidic device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection Project Objectives

We propose to develop a point-ofcare device for quantification of chemotherapeutic drugs in small body fluid samples by highly selective nanoparticle extraction and liquid crystal detection incorporated in a microfluidic lab-on-a chip device (optofluidics based)allowing the realtime drug monitoring. This will improve the therapeutic outcome and reduced health care costs.

Project Funding

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 633635.

Project Partners

• Please see project website for full partner information.

Contact Details

Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, via Amadeo 42, 20133 Milan, and I.R.C.C.S. Istituto Oncologico Giovanni Paolo II, Viale Orazio Flacco, 65, 70124 Bari, Italy T: +39 02 574 89 838 E: silke.krol@aol.com W: http://www.diachemo.eu Dr Silke Krol, Ph.D

Dr Silke Krol is a Group Leader at the Istituto Tumori “Giovanni Paolo II” in Italy. She has helped establish a new nanomedicine centre for translational cancer research, while she also works in developing new point-of-care devices for the early detection of lung cancer.

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