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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Renal dysfunction in patients with radioactive iodine-refractory thyroid cancer treated with tyrosine kinase
Hiroyuki Iwasaki1, Haruhiko Yamazaki1, Hirotaka Takasaki2
1Department of Breast and Endocrine Surgery, Kanagawa Cancer Center.
Abstract:
In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.
Insights
Tyrosine kinase inhibitors (TKIs) can negatively impact kidney function in differentiated thyroid cancer (DTC) patients. Lenvatinib showed a higher incidence of renal dysfunction compared to sorafenib, though it was reversible with dose adjustments.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Tyrosine kinase inhibitors (TKIs) are used for refractory differentiated thyroid cancer (DTC).
- Renal dysfunction is a known adverse event of TKIs, but data in DTC patients is limited.
- Understanding TKI-induced renal effects is crucial for patient management.
Purpose of the Study:
- To investigate renal function changes in DTC patients treated with TKIs.
- To evaluate the efficacy of dose reduction or withdrawal for managing TKI-induced renal dysfunction.
- To compare the renal safety profiles of sorafenib and lenvatinib in DTC.
Main Methods:
- Retrospective analysis of 73 DTC patients treated with sorafenib or lenvatinib.
- Comparison of estimated glomerular filtration rate (eGFR) and albumin levels before and after TKI therapy.
- Assessment of proteinuria incidence and degree during TKI treatment.
Main Results:
- Long-term TKI treatment negatively affected renal function in DTC patients.
- Lenvatinib was associated with more frequent heightened proteinuria, decreased eGFR, and lower albumin levels compared to sorafenib.
- Renal dysfunction was significant but appeared reversible with dose modification, except in patients with diabetes.
Conclusions:
- Renal function is negatively impacted by long-term TKI therapy for RAI-refractory DTC.
- Lenvatinib demonstrated a less favorable renal safety profile than sorafenib.
- Management strategies including dose reduction/withdrawal can mitigate TKI-induced renal dysfunction.
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