Dose adjustment for tyrosine kinase inhibitors in non‑small cell lung cancer patients with hepatic or renal function impairment (Review)

Abstract

In recent years, a number of tyrosine kinase inhibitors (TKIs) have been approved for the treatment of non-small cell lung cancer. These novel treatments exhibit improved efficacy and toxicity when compared to conventional chemotherapy agents. TKIs are administered orally, which has the advantages of improved flexibility and convenience for the patients. However, challenges have arisen in the use of these novel agents. Prescribing drugs for patients with hepatic or renal function impairment poses a challenge for clinicians due to the large pharmacokinetic variability in each individual patient. Moreover, several TKIs have been shown to cause laboratory test abnormalities normally associated with hepatic or renal injury. The aim of the present review was to discuss the effects of hepatic and renal function impairment on the pharmacokinetic variability of 17 TKIs and their potential hepatotoxicity and nephrotoxicity, and to recommend dose adjustment for patients with hepatic or renal impairment.

Clinical use of lenvatinib in patients with previous renal and/or hepatic impairment and radioiodine‐refractory differentiated thyroid cancer

“…There are no specific prevalence data for liver dysfunction in cancer patients, but it is well known that hepatic impairment interferes with clearance of drugs eliminated either by hepatic metabolism or biliary excretion, and can also affect plasma protein binding 16 . The effect of this on absorption of orally administered drugs such as TKIs can be the consequence of a reduced first‐pass effect, leading to increased bioavailability of these drugs in these patients 17 …”

“…Recommendations to consider for hepatic impairment 17 : As the liver metabolizes most drugs, hepatic impairment could decrease drug metabolism and alter exposure of a patient to drugs and their metabolites. For this reason, it is necessary to adjust doses of all concomitant drugs in addition to dose adjustments to the TKI, and to carefully monitor the patient in parallel with changes in hepatic function 17 As for renal impairment, concomitant hepatotoxic drugs should be avoided whenever possible.…”

“…As for renal impairment, concomitant hepatotoxic drugs should be avoided whenever possible. When a hepatotoxic drug is required, hepatic function monitoring, adverse event surveillance, and careful dosage adjustment must be considered 17 …”

“… 16 The effect of this on absorption of orally administered drugs such as TKIs can be the consequence of a reduced first‐pass effect, leading to increased bioavailability of these drugs in these patients. 17 …”

Pharmacokinetics of alectinib and its metabolite M4 in a patient with advanced lung adenocarcinoma undergoing hemodialysis: A case report

“…Renal impairment (RI) associated with suboptimal efficacy or significant toxicity of anticancer agents due to altered pharmacokinetics (PK) is not uncommon in non‐small cell lung cancer (NSCLC) patients 1 . Therefore, cancer management in RI patients is a major clinical challenge.…”