Cancer: for two out of three patients, drug interactions reduce risks

When it comes to cancer treatments, the whirlwind development of research leads one to reflect on the prospects that open up daily in the management of oncological diseases. But when it comes down to earth, at the patient's bedside, clinical reality brings to light how the possible polypharmacies that the person needs (and not only for the treatment of neoplasms), can interact with each other and lead to possible interactions. This may occur, with obviously different impact, in about two out of three cases. And sometimes the sub-optimal combination of drug action can even lead to hospitalisation: this is a rare condition but present in about two out of every hundred patients. In short. with increasingly targeted and combined therapies, the opportunities to keep tumours under control are growing, but these situations require an integrated and multidisciplinary approach involving oncologists and pharmacologists. And above all, they make the development of transversal and psycho-oncological skills even more urgent, integrating pharmacological risk assessment with a broader reflection on the decision-making pathway shared with the patient, also thanks to a more widespread use of PROs (Patient Reported Outcomes), health outcomes assessed directly by the patient and based on his or her perception of the disease and treatment. These perspectives are pointed out by the experts present at the conference 'Drug interactions in clinical risk management: a reasoned guide to decision-making (and to the ethics of choice)', held at the State University of Milan.

'In cancer treatment, the risk of drug interactions is increased by the concomitant use of supportive drugs such as antiemetics, anticonvulsants, analgesics and corticosteroids,' points out Gianluca Vago, Director of the Department of Oncology and Haemato-Oncology (DIPO) at Milan State University. The high prevalence of polypharmacy in cancer patients poses a unique set of challenges, as it is capable of compromising the efficacy and safety of anti-cancer treatments, leading to reduced therapeutic effect or unexpected adverse events'. Let's be clear. In addition to problems for the patient and caregivers, this condition also opens the way to costs for the health service due to possible 'mixing' with drugs (and others) that the patient self-prescribes. "In oncology, the issue is particularly delicate," confirms Gabriella Pravettoni, Professor of Psychology of Decisions at the DIPO of the State University of Milan and Director of the Division of Psycho-oncology at the IEO. The therapeutic choice, especially in cases of advanced or metastatic disease, implies not only knowledge of interactions, but also an ethical assessment of the expected benefit. It is necessary to ask how far it is appropriate to go in proposing a treatment and how to integrate clinical expertise with the patient's subjectivity, values, fears and priorities. The ethics of the therapeutic choice and psycho-oncological support in the decision-making process thus become a balancing act between appropriateness, proportionality and respect for autonomy'.

'The diversity of cancer treatments, including chemotherapy, targeted therapies, hormonal agents, monoclonal antibodies and drug-conjugated antibodies, adds complexity to assessments of drug interactions,' stresses Romano Danesi, Professor of Pharmacology at the DIPO of the Milan State University. 'Each class of drugs has unique characteristics that require an individualised approach. The metabolism of each drug is influenced by multiple factors, including genetics, age, liver and kidney function, and diet. Despite advances in therapies, drug interactions are often underestimated in clinical practice. Even the interaction between various drugs, foods and supplements can lead to potential synergistic or antagonistic effects, which are sometimes not recognised'. The numbers, however, tell how the availability of new oral anticancer molecules in clinical practice has increased the complexity of managing drug interactions. A study of over 5,600 cases of drug interactions found that targeted therapies accounted for 63% of interactions, compared to cytotoxic agents (21%) and hormonal therapies (19%). "Immunotherapy is also changing the natural history of many malignancies," explains Giuseppe Curigliano, Professor of Medical Oncology at the DIPO of the State University of Milan and President-elect of ESMO (European Society of Medical Oncology). "Reduced efficacy of immunoncological drugs can occur when administered simultaneously with antibiotics, corticosteroids or proton pump inhibitors. Immunoncological therapies rely on restoring T-cell responses, which may be impaired by alterations in the balance of the gut microbiota or by immunosuppression. Multidisciplinary collaboration between oncologists and pharmacologists in clinical practice allows for the prediction and management of drug interactions'.

A cultural change of great significance in oncology in recent years is the increasing focus on patient-reported outcomes through standardised questionnaires, the Patient-Reported Outcome (PRO). "PROs are very important tools in the evaluation of anti-cancer treatments and quality of life, because they add data reported directly by patients, without any filter, expanding knowledge about the value of therapies,' Pravettoni further explains. 'It is important to improve the timeliness with which this information is collected. Today, few hospitals take measures to systematically monitor patients' symptoms. A change of pace is needed, so that the collection and analysis of patients' views on the outcome of a treatment does not remain just a theoretical principle, but becomes an indispensable method'. PROs, in the end, can foster 'patient empowerment', because they allow patients to express themselves autonomously, also bringing out side effects characterised by a strong subjective component.

'Competence in the management of drug interactions requires the ability to synthesise, dialogue and shared multidisciplinary responsibility in clinical decision-making,' concludes Ketti Mazzocco, associate professor of Psychology at the DIPO of the Milan State University and psycho-oncologist at the IEO. 'Think of the effect that psychological state has on the prognosis of cancer patients, as a recent article published in 'Nature' points out. The focal point is to look at the complexity of the system: I take as an example the depressive state, which not only decreases the effectiveness of pharmacological treatments by acting on behaviour, but also contributes to a change in the intestinal microbiota, neuroinflammation and general systemic inflammation, favouring disease progression. A key strategy to prevent drug interactions lies in informing patients and carers about the risks associated with polypharmacy and non-adherence to treatment. This first National Conference was born with the aim of building a bridge between clinical pharmacology and psycho-oncology, between science and relationship, offering concrete tools to guide the therapeutic choice in respect of the person, the context and the complexity'.