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Lenvatinib: Uses, Mechanism & Side Effects
Lenvatinib is a prescription cancer medication that inhibits tumor growth by blocking key signaling pathways. It is used to treat several types of advanced cancer.
Add as Preferred SourceThings worth knowing about "Lenvatinib"
Lenvatinib is a prescription cancer medication that inhibits tumor growth by blocking key signaling pathways. It is used to treat several types of advanced cancer.
What is Lenvatinib?
Lenvatinib is a targeted therapy belonging to the class of tyrosine kinase inhibitors (TKIs). It is used in oncology to treat certain cancers where uncontrolled tumor growth is driven by specific molecular signaling pathways. Lenvatinib is marketed under the brand name Lenvima and is taken orally as a capsule once daily.
Indications
Lenvatinib has been approved by the European Medicines Agency (EMA), the U.S. Food and Drug Administration (FDA), and other regulatory authorities for the following conditions:
- Differentiated thyroid cancer (DTC): For patients with locally advanced or metastatic, radioiodine-refractory thyroid cancer.
- Hepatocellular carcinoma (HCC): As a first-line treatment for unresectable liver cancer.
- Renal cell carcinoma (RCC): In combination with everolimus following prior anti-VEGF therapy.
- Endometrial carcinoma: In combination with pembrolizumab for advanced uterine cancer that has progressed after platinum-based chemotherapy.
Mechanism of Action
Lenvatinib works by simultaneously inhibiting multiple receptor tyrosine kinases -- enzymes that play a central role in the signaling networks driving tumor cell growth and the formation of new blood vessels that supply the tumor. Specifically, lenvatinib blocks:
- VEGFR 1, 2, and 3 (vascular endothelial growth factor receptors): Inhibits tumor angiogenesis (the formation of new blood vessels that feed the tumor).
- FGFR 1, 2, 3, and 4 (fibroblast growth factor receptors): Inhibits cell proliferation and survival.
- PDGFRa (platelet-derived growth factor receptor alpha): Affects the tumor microenvironment.
- RET and KIT: Important oncogenes implicated in various cancers.
By simultaneously blocking these pathways, lenvatinib suppresses both the direct proliferation of tumor cells and their blood supply, thereby limiting tumor growth and spread.
Dosage and Administration
Lenvatinib is taken orally once daily as a capsule, with or without food. The recommended dose depends on the indication and the patient body weight:
- Differentiated thyroid cancer: 24 mg per day
- Hepatocellular carcinoma: 12 mg per day (body weight ≥ 60 kg) or 8 mg per day (body weight < 60 kg)
- Renal cell carcinoma: 18 mg per day (in combination with everolimus 5 mg)
- Endometrial carcinoma: 20 mg per day (in combination with pembrolizumab)
Dose reductions or temporary interruptions may be necessary in the event of significant side effects.
Side Effects
Like all cancer medications, lenvatinib can cause side effects. The most common include:
- High blood pressure (hypertension): Very common; regular blood pressure monitoring is required.
- Fatigue and weakness
- Diarrhea and abdominal pain
- Nausea and vomiting
- Weight loss and decreased appetite
- Mouth sores (stomatitis/mucositis)
- Hand-foot syndrome (palmar-plantar erythrodysesthesia): Pain, redness, and swelling of the palms and soles
- Hypothyroidism (underactive thyroid)
- Thromboembolic events (blood clots) and bleeding
Rare but serious side effects include liver dysfunction, cardiac events (e.g., QT prolongation), and impaired wound healing. Patients should promptly report any unexpected symptoms to their medical team.
Contraindications and Precautions
Lenvatinib should not be used or should only be used under strict medical supervision in the following situations:
- During pregnancy and breastfeeding (due to teratogenic potential)
- In patients with severe hepatic or renal impairment
- In patients with known hypersensitivity to the active substance
- Shortly before or after surgical procedures (risk of impaired wound healing)
Regular monitoring of blood pressure, kidney function, liver enzymes, and thyroid hormone levels is required during therapy.
References
- European Medicines Agency (EMA): Lenvima (lenvatinib) - Summary of Product Characteristics and EPAR. Available at: https://www.ema.europa.eu (accessed 2024)
- Schlumberger M. et al. - Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer. New England Journal of Medicine, 372(7):621-630, 2015.
- Kudo M. et al. - Lenvatinib versus Sorafenib in First-Line Treatment of Patients with Unresectable Hepatocellular Carcinoma. The Lancet, 391(10126):1163-1173, 2018.
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