Abstract
Drug–drug interactions (DDIs) can affect both treatment efficacy and toxicity. We used Drug-PIN® (Personalized Interactions Network) software in colorectal cancer (CRC) patients to evaluate drug–drug–gene interactions (DDGIs), defined as the combination of DDIs and individual genetic polymorphisms. Inclusion criteria were: (i) stage II-IV CRC; (ii) ECOG PS (Performance status sec. Eastern coperative oncology group) ≤2; (iii) ≥5 concomitant drugs; and (iv) adequate renal, hepatic, and bone marrow function. The Drug-PIN® system analyzes interactions between active and/or pro-drug forms by integrating biochemical, demographic, and genomic data from 110 SNPs. We selected DDI, DrugPin1, and DrugPin2 scores, resulting from concomitant medication interactions, concomitant medications, and SNP profiles, and DrugPin1 added to chemotherapy drugs, respectively. Thirty-four patients, taking a median of seven concomitant medications, were included. The median DrugPin1 and DrugPin2 scores were 42.6 and 77.7, respectively. In 13 patients, the DrugPin2 score was two-fold higher than the DrugPin1 score, with 7 (54%) of these patients experiencing severe toxicity that required hospitalization. On chi-squared testing for any toxicity, a doubled DrugPin2 score (p = 0.001) was significantly related to G3–G4 toxicity. Drug-PIN® software may prevent severe adverse events, decrease hospitalizations, and improve survival in cancer patients.
Highlights
To the best of our knowledge, Drug-PIN® is the first intelligent system to combine data regarding concomitant medications and a patient’s pharmacogenomic profile, DDIs, and metabolic data, resulting in a global score that can be used by the physician to better predict clinical outcomes and eventually prevent severe toxicities related to chemotherapy, to support any choices of therapeutic variation in the light of known interferences between drugs used in the therapy or unfavorable biochemical phenotypes
Our Drug-PIN® platform gathers all of the patient’s traits, including gender, age, weight, lifestyle habits, concomitant medications, and pharmacogenomics; we are able to summarize all of these aspects in a single global score
These single-nucleotide polymorphisms (SNPs) have been described in several scientific reports, which have demonstrated a relationship with functional metabolic changes in enzymes, receptors, and transporters, affecting both pharmacokinetic and pharmacodynamic aspects
Summary
Aside from well-known anticancer drugs, patients often take other medications to treat different conditions, such as diabetes and hypertension, among others, which could lead to severe changes in pharmacokinetic (absorption, distribution, metabolism, elimination) and pharmacodynamic properties, making this an even more complex scenario [2,3,4]. Pharmaceuticals 2021, 14, 67 lead to severe changes in pharmacokinetic (absorption, distribution, metabolism, elimina of 12 tion) and pharmacodynamic properties, making this an even more complex scenario [2–. Is relevantisinthe older patientsofbecause cancer and ageing are profile, both causes of important knowledge a patient’s pharmacogenomic includpolypharmacy in thisofpopulation [5,6,7]. Enzyme superfamily and other genes affecting ing all cytochromes the P450 (CYPs) important the knowledge of a patient’s pharmacogenomic profile, including thoseEqually properties, such asisP-glycoprotein, ATP-binding cassette transporters, as well as deall cytochromes of the P450 Is relevantisinthe older patientsofbecause cancer and ageing are profile, both causes of important knowledge a patient’s pharmacogenomic includpolypharmacy in thisofpopulation [5,6,7]. enzyme superfamily and other genes affecting ing all cytochromes the P450 (CYPs) important the knowledge of a patient’s pharmacogenomic profile, including thoseEqually properties, such asisP-glycoprotein, ATP-binding cassette transporters, as well as deall cytochromes of the P450
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