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Drug interactions with solid tumour-targeted therapies

Audrey Thomas-Schoemann1, Benoit Blanchet1, Christophe Bardin2

  • 1Centre d'Étude et de Recours aux Inhibiteurs de l'Angiogénèse, Paris, France; UF de Pharmacocinétique et Pharmacochimie, Groupement des Hôpitaux Paris Centre, 75014 Paris, France.

Critical Reviews in Oncology/Hematology
|September 18, 2013
PubMed

Insights

Drug interactions involving targeted cancer therapies like TKIs and mTOR inhibitors are a significant clinical concern, particularly with polypharmacy in elderly patients. Understanding these interactions is crucial to manage anticancer drug exposure and prevent resistance or toxicity.

Area of Science:

  • Oncology
  • Pharmacology
  • Drug Metabolism

Background:

  • Drug interactions (DDIs) pose a significant challenge in cancer treatment, especially with targeted therapies.
  • Polypharmacy in elderly patients with cancer and comorbidities increases the risk of DDIs.
  • Tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors are primarily metabolized by cytochrome P450 enzymes, heightening DDI risks.

Purpose of the Study:

  • To provide a comprehensive review of DDIs involving FDA-approved targeted therapies for solid tumors.
  • To examine interactions between targeted anticancer drugs and medicinal herbs or other drugs.
  • To offer clinical practice guidelines for oncologists and pharmacists managing these interactions.

Main Methods:

  • Systematic review of existing literature on drug-drug interactions.
  • Focus on targeted therapies approved by the FDA for over three years.
  • Inclusion of interactions with medicinal herbs and other commonly used drugs.

Main Results:

  • Identified key DDIs associated with specific targeted therapies (sorafenib, sunitinib, erlotinib, gefitinib, imatinib, lapatinib, everolimus, temsirolimus).
  • Highlighted how DDIs can alter anticancer drug exposure, potentially leading to resistance or toxicity.
  • Cataloged interactions involving cytochrome P450 metabolism.

Conclusions:

  • Managing DDIs is critical for optimizing cancer treatment outcomes with targeted therapies.
  • Awareness of potential interactions with concomitant medications and herbal products is essential.
  • Guidelines are provided to assist healthcare professionals in clinical decision-making regarding DDIs in cancer patients.
Keywords:
5-fluorouracile5FUABCATP-binding cassetteAUCBCRPC(max)CYPDDIDrug–drug interactionsEIAEDSHerb–drug interactionsMammalian target of rapamycin inhibitorsP-glycoproteinP-gpPharmacokineticsSolid tumourTKITargeted therapiesTyrosine kinase inhibitorsUDP-glucuronyl transferaseUGTarea under the curvebreast cancer resistance proteincytochrome p450 enzymesdrug–drug interactionsenzyme-inducing antiepileptic drugsmTORmammalian target of rapamycinmaximum (peak) plasma concentrationtyrosine kinase inhibitor

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