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ESMO October 20-24, 2023; Madrid Spain

Global DDI Solutions

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The ESMO 2023 (European Society for Medical Oncology) was held in Madrid, Spain. Specialists, oncologists, pharmacists, students came together to share knowledge about oncology. In this post interesting presentations about drug-drug management in patients with cancer are summarized.

Frequency and clinical relevance of drug-drug interactions with oxycodone among patients with cancer

L. Hulskotte, et al.

Oxycodone is commonly used in patients with cancer and is metabolized by cytochrome P (CYP) 3A4 enzymes. Therefore, oxycodone is common a victim of drug-drug interactions (DDIs). Oxycodone combined by CYP3A4 inducer could result in loss of efficacy and combined with CYP3A4 inhibitor in adverse drug reactions. The frequency and pharmacological and clinical relevance of DDIs between oxycodone and perpetrators were studied in patients with cancer.

A cross-sectional study was performed between 1 September 2021 and 1 September 2022 in Deventer hospital. Pharmacy records were used to study concomitant use of oxycodone and DDI perpetrators and the frequency of multiple interactions. These perpetrators were determined from Lexicomp®, Micromedex®, the Dutch Kennisbank® and Dutch Commentaren Medicatiebewaking®. The relevance of the identified perpetrators were examined by a clinical pharmacologist and a medical oncologist.

254 records with oxycodone use were found. In 227 records, at least 1 clinically relevant perpetrator was found. Of these, 210 were clinically relevant. In total, 80 perpetrators were identified, with 65 (81.3%) being considered clinically relevant. In 21 (8.3%) records with oxycodone use, interactions were observed. The Dutch compendia generally classified DDIs with oxycodone as less relevant than Lexicomp and Micromedex.

In conclusion, a high frequency of pharmacological and clinical relevant perpetrators of DDIs and double interactions with oxycodone were observed. To improve the pharmacovigilance, drug interaction compendia used in Dutch healthcare should be revised in according international drug compendia.

Personalised dosing of oral targeted therapies in oncology: The era of therapeutic drug monitoring

M.B.A. van der Kleij, et al.

Oral targeted therapy in oncology is common given in standard fixed dose to patients. The high interpatient variability in pharmacokinetics (PK), may result in overdosing or underdosing causing toxicity or loss of efficacy. In addition, oral targeted therapies, such as abiraterone, imatinib, sunitinib and pazopanib, have increased risk of drug-drug interactions (DDIs), due to metabolism by or influence on cytochrome P (CYP) enzymes or transporters. These DDIs have influence on the blood concentrations of these drugs. Personalised dosing through therapeutic drug monitoring may optimize treatment outcome.

This study is an ongoing research, what is focused on feasibility, efficacy, and tolerability of TDM of several oral targeted therapies. PK-values are collected 4-8-12 weeks after initiating oral targeted therapy and every 12 weeks thereafter. Based on efficacy target and measured concentration in patients, recommendations are given to reach the target efficacy. Examples of recommendations are dose adjustment, intake with food, split of intake moments, emphasize compliance and adjustment of interacting medication. An intervention is successful when PK-level is above target and no dose limiting toxicity within one month took place.

41.3% (n=378) of 916 evaluable patients had all PK-levels above target, while 58.7% (n=538) had ≥1 PK–level below target. PK-guided intervention was possible in 55.4% (n=298) and was successful for 38.3% of patients below target. The total patients above PK-level targets increased to 63.8%, a gain of 22.5%.

In conclusion, TDM can be useful to optimize treatment with oral targeted therapies. Before TDM implementation in the practice, TDM should be more evaluated for these therapies. For this, established exposure-response and -toxicity relationships are required. When TDM will be standard of care for oral targeted therapies, it can also be used for DDI management.