Drug-Drug Interactions (DDI) and Personalized Medicine in Oncology

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 June 2024 | Viewed by 1416

Special Issue Editors


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Guest Editor
Medical Oncology Unit A, Umberto I University Hospital, Sapienza University, 00100 Rome, Italy
Interests: genito-urinary cancer; chemotherapy; target therapy
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Guest Editor
Department of Radiological, Oncological and Pathological Sciences, Medical Oncology Unit, Umberto I Hospital, Sapienza University, 00161 Rome, Italy
Interests: breast cancer; head and neck cancer; immunotherapy

Special Issue Information

Dear Colleagues,

Drug‒drug interactions (DDIs) are one of the main aspects within the personalized medicine field that concern the treatment of cancer patients, especially when multiple oral or non-oral drugs are being used. However, the clinical relevance of these interactions is not always investigated. DDIs can be pharmaceutical, pharmacokinetic, or pharmacodynamic. They can also be wanted (e.g., the use of ciclosporin to enhance the oral bioavailability of paclitaxel); unwanted (e.g., a combination of the antiviral agent sorivudine and oral fluorouracil analogues can lead to fatal complications); between cytotoxic drugs, cytotoxic drugs, and non-cytotoxic drugs; or with pharmaceutical vehicles. More attention should be paid to the recognition of potential drug interactions to especially identify any effect in terms of toxicity as well as activity in oncological and non-oncological drugs. Therefore, we search for articles (reviews or original papers) about DDIs in cancer patients, regardless of the type of tumor, to provide more information about this less-explored field.

Dr. Michela Roberto
Prof. Dr. Andrea Botticelli
Guest Editors

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Published Papers (1 paper)

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Research

15 pages, 1558 KiB  
Article
Impact of a Moderate CYP3A4 Inducer (Bosentan) on Lurbinectedin Pharmacokinetics and Safety in Patients with Advanced Solid Tumors: An Open-Label, Two-Way, Crossover, Phase Ib Drug–Drug Interaction Study
by Irene Moreno, Tatiana Hernández, Emiliano Calvo, Salvador Fudio, Carmen Kahatt, Cristian Fernández, Jorge Luis Iglesias, Gema Corral, Laura Pérez-Ramos, Lola Montilla, Ali Zeaiter and Rubin Lubomirov
Pharmaceuticals 2024, 17(2), 182; https://doi.org/10.3390/ph17020182 - 30 Jan 2024
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Abstract
This open-label, two-way, crossover, phase Ib drug–drug interaction study investigated whether the pharmacokinetics (PKs) and safety profile of lurbinectedin (LRB) are affected by co-administration of a moderate CYP3A4 inducer (bosentan, BOS) in adult patients with advanced solid tumors. Eleven patients were randomly assigned [...] Read more.
This open-label, two-way, crossover, phase Ib drug–drug interaction study investigated whether the pharmacokinetics (PKs) and safety profile of lurbinectedin (LRB) are affected by co-administration of a moderate CYP3A4 inducer (bosentan, BOS) in adult patients with advanced solid tumors. Eleven patients were randomly assigned to Sequence 1 (LRB + BOS in Cycle 1 [C1] and LRB alone in Cycle 2 [C2]) or Sequence 2 (LRB alone in C1 and LRB + BOS in C2), and finally, eight patients (four per sequence) were considered evaluable for PK assessment. LRB (3.2 mg/m2, 1 h [h], intravenous) was administered alone or combined with multiple BOS administration (125 mg/12 h oral; 5.5 days). Co-administration with BOS decreased the systemic total exposure (area under the curve, AUC) of LRB by 21% for AUC0–t and 20% for AUC0–∞ and increased clearance by 25%. Co-administration with BOS did not significantly modify the unbound plasma LRB PK parameters. BOS increased the conversion of LRB to its metabolite M1, with no changes on its metabolite M4. The LRB safety profile was consistent with the toxicities previously described for this drug. No differences in terms of toxicity were found between LRB with and without BOS. In summary, the magnitude of the observed changes precludes a clinically relevant effect of BOS co-administration on LRB exposure and its safety profile. Full article
(This article belongs to the Special Issue Drug-Drug Interactions (DDI) and Personalized Medicine in Oncology)
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