Pharmacokinetic drug interactions of oral anticancer drugs

Summary

Over the past 20 years, oral anticancer drugs have increased in importance for the treatment of solid tumors and hematological diseases. Pharmacokinetic interactions with these drugs are often of clinical relevance. They can occur at the level of absorption, metabolism or excretion. The influence of food on the bioavailability of drugs—referred to as positive or negative food effect—often requires instruction of the patients about appropriate administration of oral anticancer drugs (e.g., to take a drug in the fasted state or with a meal). The absorption of tyrosine kinase inhibitors, representing weak bases, depends on the pH value in the stomach, this leading to possible interactions with treatments that alter gastric pH such as proton pump inhibitors or H2 receptor antagonists, which in individual cases can be prevented by adhering to stipulated time intervals. Since many tyrosine kinase inhibitors, but also enzyme inhibitors and antihormonal agents are metabolized via the cytochrome P450 enzyme system (mainly CYP3A4, but also CYP1A2, CYP2D6, CYP2C9, CYP2C19), interactions at the level of metabolism play a central role. In combination with moderate and potent CYP enzyme inhibitors and inducers, special caution is required. However, clinically relevant interactions may also occur in CYP-independent degradation pathways, e.g., degradation of 6‑mercaptopurine via xanthine oxidase or catabolism of fluoropyrimidines via dehydropyrimidine dehydrogenase.