Elsevier

The Lancet Oncology

Volume 5, Issue 8, August 2004, Pages 489-496
The Lancet Oncology

Review
Drug interactions in oncology

https://doi.org/10.1016/S1470-2045(04)01528-1Get rights and content

Summary

Drug interactions are an ongoing concern in treatment of cancer, especially when cytotoxic drugs are being used. However, the clinical relevance of these interactions is not always investigated. Drug interactions can be pharmaceutical, pharmacokinetic, or pharmacodynamic. They can also be wanted (eg, use of ciclosporin to enhance the oral bioavailability of paclitaxel); unwanted (eg, 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. Potential interactions between anticancer drugs and over-the-counter or alternative medicines and herbs should not be underestimated. More attention should be given to the recognition of potential drug interactions in the preclinical and early clinical development phase of a new anticancer drug. Here, we provide a comprehensive overview of drug interactions, with selected examples.

Section snippets

Pharmaceutical interactions

Pharmaceutical interactions occur when two compounds interact because of they are incompatible either physically or chemically. An example is when admixtures for infusion are prepared: when the thiol compound mesna is added to a cisplatin solution, it inactivates the platinum drug by forming a covalent mesna–platinum adduct.13 Other examples include the rapid degradation of mitomycin into inactive mitosenes when the drug is dissolved in a 5% dextrose infusion fluid (pH 4–5);14 and the

Pharmacokinetic interactions

Pharmacokinetic interactions arise as a result of the four simple, almost indistinguishable, kinetic principles: absorption, distribution, metabolism, and elimination. Metabolising enzymes or drug transporters are often involved in these processes.

Prediction of drug interactions

Drug interactions can cause many clinical problems. Ideally, all this knowledge is available before a new drug enters clinical testing: although translation of preclinical data to the clinic remains cumbersome and will never be perfect, we should always aim for the maximum attainable therapeutic effect. It is therefore important to continue the collection of more mechanistic and theoretical knowledge about drug interactions. New in vitro and in vivo techniques are also very useful in this

Search strategy and selection criteria

Data for this review were identified by searches in PubMed and references cited in relevant articles. Search items included: “drug interactions”, “drug–drug interactions”, and “oncology”. Only papers published in English were included. Radiopharmaceuticals, hormones, immunotherapeutics used in oncology were considered to be beyond the scope of this report.

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