Generic Name

Jevtana

Mechanism

• Calcineurin inhibition: Zotarolimus binds FK-binding proteins (FKBP12) and suppresses calcineurin phosphatase activity, blocking IL‑2 transcription and T‑cell activation.
• Local cytotoxicity: Sustained release of zotarolimus from polyvinyl alcohol beads induces apoptosis of tumor endothelial and malignant cells.
• Anti‑angiogenic activity: Inhibition of NF‑κB signaling reduces vascular endothelial growth factor (VEGF) production, starving the tumor.

The bead’s embolic action occludes feeding arteries, causing ischemia and enhancing drug uptake.

Pharmacokinetics

• Administration: Intravenously introduced via a catheter into the hepatic artery, then retained within the microsphere matrix.
• Absorption: Minimal systemic absorption; <2 % of the total drug load enters the bloodstream.
• Distribution: Local perfusion within the tumor microenvironment; negligible diffusion to contralateral liver or distant tissues.
• Metabolism: Primarily hepatic CYP3A4‑mediated; however, local delivery reduces systemic metabolism burden.
• Elimination: Excreted via bile and feces; renal clearance is minimal.
• Half‑life: The drug remains within beads for up to 48 h, with a biological half‑life of ~1–3 days once released.

Indications

• Unresectable hepatocellular carcinoma (HCC): Patients with preserved liver function (Child‑Pugh A/B).
• Metastatic colorectal carcinoma to the liver: For oligometastatic lesions unsuitable for systemic chemotherapy or resection.
• Other hepatic malignancies: Neuroendocrine tumor metastases, cholangiocarcinoma, and selected sarcomas—when conventional transarterial chemoembolization shows limited benefit.
• Adjunct to systemic therapy: In combination with tyrosine‑kinase inhibitors or checkpoint inhibitors to enhance tumor control.

Contraindications

• Contraindications
• Known hypersensitivity to zotarolimus or bead constituents.
• Severe hepatic impairment (Child‑Pugh C).
• Uncorrected coagulopathy (platelet  1.5).
• Non‑cirrhotic portal vein thrombosis involving > 50 % of portal flow.
• Warnings
• Osteonecrosis of the jaw: Rare but possible with immunosuppressive agents; educate patients.
• Non‑target embolization: May cause limb ischemia, biliary injury, or gastric ulceration.
• Hypertension: Monitor BP due to systemic immunosuppressants.

Dosing

Follow‑up imaging within 4–6 weeks to assess necrosis; subsequent sessions may be performed every 6–8 weeks if residual viable tumor persists.

Adverse Effects

Common (≥ 10 % incidence)
• Post‑embolization syndrome:
• Abdominal pain
• Nausea/vomiting
• Transient elevation of AST/ALT (≤ 3× ULN)
• Fever ≤ 38 °C for ≤ 48 h

Serious (≤ 1 % incidence)
• Non‑target embolization: limb ischemia, biliary necrosis, gastric ulceration
• Severe hepatic insufficiency (encephalopathy, coagulopathy)
• Severe hypertension or nephrotoxicity
• Thrombocytopenia requiring transfusion
• Osteonecrosis of the jaw (rare)

Monitoring

• Liver function tests: Every 48–72 h for the first week, then weekly.
• Complete blood count: Platelets, hemoglobin, WBC.
• Inflammatory markers: CRP, ESR (if signs of infection).
• Imaging: Contrast‑enhanced CT/MRI at 1–3 months post‑treatment to evaluate necrosis and residual disease.
• Blood pressure: Monitor for > 10 mmHg systolic rise.
• Pain assessment: Use a 0‑10 numeric rating scale.

Clinical Pearls

• Bead size matters: 100 µm beads deliver deeper tumor penetration but increase non‑target embolization risk; 300 µm beads are safer for superficial lesions.
• Pre‑treatment embolic material: Using bland microspheres in a staging session can delineate tumor vascularity before drug‑eluting bead therapy.
• Drug–bead ratio: Over‑loading beads (> 25 mg) may cause premature release during injection; adhere to manufacturer guidelines.
• Combine with systemic agents: Sequencing Jevtana with sorafenib or lenvatinib may enhance efficacy but monitor for additive hepatotoxicity.
• Avoid non‑selective catheterization: Unintentional lodging in the gastroduodenal artery can cause gastric necrosis—use microcatheters and confirm positioning with fluoroscopy.
• Patient education: Counsel patients on expected post‑embolization pain and when to seek urgent care (e.g., persistent vomiting or abdominal rigidity).

--
• Jevtana offers a localized, potent anti‑angiogenic and cytotoxic approach for hepatic malignancies, minimizing systemic exposure while delivering targeted therapy. Proper patient selection, meticulous catheter technique, and vigilant post‑procedure monitoring are essential to maximize benefit and minimize complications.