Project name: Innovative tools for therapeutic drug monitoring in cancer patients: toward bed side testing.
Responsible: Dr. Marco Agostini
Project start – Project end: 01/02/2014 – 31/01/2017
Budget: € 200.000
Staff: Marco Agostini; Sara Crotti; Sara D’Aronco
Project name: Application of Advanced Nanotechnology in the Development of Cancer Diagnostic Tools.
Responsible: Dr. Pietro Traldi, Dr. Marco Agostini
Project start – Project end: 01/06/2015 – 31/05/2017
Staff: Pietro Traldi; Marco Agostini; Sara Crotti; Sara D’Aronco
A new generation of analytical tools are necessary to respond the timely need of early diagnosis, reliable prognosis and effective treatment of cancer patients. Our work hypothesis is that the availability of new dedicated devices for cancer patients, to sensitively measure in real-time the concentrations drugs to perform the TDM will allow to improve the therapy effectiveness. Anticancer drugs possess a narrow therapeutic window and to be effective, the drug concentrations have to remain in an appropriate range. About 30–60% of drugs are used without any benefit for patients because of individual differences in drug absorption, metabolism and excretion. Moreover, the coexistence of genetic polymorphisms in transporters, enzymes, targets and receptors could result in appearance of toxicities. Therapy personalization protocols aim to optimize the treatment according to patient’s characteristics and thus, the therapeutic drug monitoring (TDM) is crucial for this approach. Nevertheless, TDM has not been established in routine practice, and dose decreases are performed only in case of unacceptable dose-limiting toxicities (DLTs).
In this frame, we proposed the possibility to perform quantitative analysis of critical antineoplastic drugs by faster analytical approaches, such as the MALDI-TOF and the ambient ionization mass spectrometry. Two remarkable aspects seem to make these analytical methods feasible for TDM purposes: they are faster than traditional LC-MS approaches and they require of only few microlitres of human plasma samples for the analysis. This can, on the one hand, improve the patient’s compliance when multiple blood withdrawn are needed and, on the other hand, render feasible an important challenge like the TDM in paediatric patients.
Our approaches have been positively employed to perform the TDM in several patients under CPT-11 therapy during the drug infusion time by MALDI-TOF, minimizing the time necessary to this kind of analysis. Actually, ours investigations are devoted to develop a new TDM approach for the drug Imatinib, which is used to treat chronic myelogenous leukemia (CML) both in adults and children.