LETINIB
LETINIB

LETINIB

Lenvatinib 4mg/ Lenvatinib 10mg
Net Qty- 30 capsules
Self-Life- 2 Years

πŸ’Š Letinib (Lenvatinib ) is an oral multikinase inhibitor used primarily in the treatment of several types of cancers, especially those involving the thyroid, kidney, liver, and endometrium.

πŸ“‹ Key Facts

  • Class: Tyrosine kinase inhibitor (TKI)
  • Administration: Oral capsule/tablet, taken once daily
  • Common Doses: 4 mg, 10 mg (doses vary by cancer type and combination therapy)

USE

🎯 LetinibΒ (Lenvatinib) is used to treat several types of advanced or metastatic cancers, especially when standard treatments are not effective. Here’s a breakdown of its approved and common uses:

βœ… Differentiated Thyroid Cancer (DTC)

  • Use: For radioactive iodine–refractory DTC (papillary, follicular, or HΓΌrthle cell types)
  • Effect: Slows tumor growth in patients who no longer respond to RAI treatment

βœ… Hepatocellular Carcinoma (HCC)

  • Use: First-line treatment of unresectable liver cancer
  • Eligibility: Patients with Child-Pugh class A liver function
  • Effect: Improves overall survival and delays disease progression

βœ… Renal Cell Carcinoma (RCC)

  • Use: In combination with everolimus for advanced RCC after failure of one prior anti-angiogenic therapy
  • Effect: Synergistic effect with everolimus to suppress tumor growth

βœ… Endometrial Carcinoma

  • Use: In combination with pembrolizumab (an immune checkpoint inhibitor) for patients with:
  • Advanced or recurrent disease
  • No microsatellite instability-high (MSI-H) or mismatch repair deficiency
  • Effect: Enhances immune response and slows disease progression

πŸ”¬ Off-Label / Investigational Uses

  • Ongoing clinical trials for:
  • Head and neck cancers
  • Non-small cell lung cancer (NSCLC)
  • Ovarian cancer
  • Melanoma

Key Benefits

🌟 Key Benefits of Letinib (Lenvatinib)

Lenvatinib is a multikinase inhibitor with proven effectiveness across several types of cancer. Here are the key benefits that make it a vital treatment option for patients:

βœ… Efficacy Across Multiple Cancer Types

  • Thyroid Cancer (DTC): In patients with radioactive iodine-refractory thyroid cancer, Lenvatinib shows high response rates, significantly improving progression-free survival (PFS).
  • Hepatocellular Carcinoma (HCC): In combination with sorafenib, it improves overall survival and progression-free survival, offering a viable first-line treatment option.
  • Renal Cell Carcinoma (RCC): When combined with everolimus, Lenvatinib improves tumor response and PFS in patients previously treated with VEGF-targeted therapies.
  • Endometrial Carcinoma: In combination with pembrolizumab, it shows significant tumor response rates in advanced or recurrent endometrial cancer, including mismatch repair-proficient (pMMR) tumors, which are typically resistant to immunotherapy alone.

βœ… Promotes Tumor Shrinkage and Disease Control

  • Rapid onset of action: Lenvatinib has shown the ability to shrink tumors and stabilize disease quickly, often within the first few months of treatment.
  • High response rates: For thyroid and liver cancers, response rates can be as high as 60–65% in some cases, with significant tumor reduction seen in many patients.

βœ… Well-Tolerated in Most Patients

  • While Lenvatinib does come with side effects, they are generally manageable with dose adjustments and supportive care.
  • Effective management of side effects: By following regular monitoring and modifying the dose as necessary, many patients can maintain a good quality of life during treatment.

βœ… Convenient Oral Administration

  • Once-daily oral dose: Lenvatinib is taken once daily, offering ease of use and flexibility compared to intravenous therapies or frequent hospital visits.

βœ… Combination Therapy Potential

  • Lenvatinib can be effectively combined with immunotherapy agents (e.g., pembrolizumab) or other targeted therapies (e.g., everolimus) to boost efficacy and improve treatment outcomes for various cancers, including endometrial and renal cancers.

βœ… Approved for Multiple Indications

  • Lenvatinib is approved for use in several cancers, including differentiated thyroid cancer (DTC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and endometrial carcinoma.
  • Versatile treatment options make Lenvatinib an important part of personalized cancer care.

βœ… Enhances Immunotherapy Response

  • When used with pembrolizumab, Lenvatinib improves the immune response to tumors, especially in cancers that are immune-resistant on their own (e.g., endometrial cancer), by increasing immune cell access to the tumor.

Mechanism
of Action

βš™οΈΒ Lenvatinib is a multikinase inhibitor that targets specific receptor tyrosine kinases (RTKs) involved in tumor growth, angiogenesis (blood vessel formation), and cancer progression.

πŸ”¬Β Key Targets Inhibited by Lenvatinib

Lenvatinib selectively inhibits the following receptors:

  1. VEGFR 1, 2, 3 – Vascular Endothelial Growth Factor Receptors
    β†’ Blocks tumor blood vessel growth (anti-angiogenic effect)

  2. FGFR 1–4 – Fibroblast Growth Factor Receptors
    β†’ Inhibits cell proliferation and tumor growth

  3. PDGFRΞ± – Platelet-Derived Growth Factor Receptor Alpha
    β†’ Reduces cancer cell migration and angiogenesis

  4. RET – Rearranged During Transfection Proto-Oncogene
    β†’ Affects thyroid cancer growth, especially in RET-mutant tumors

  5. KIT – Stem Cell Growth Factor Receptor
    β†’ Involved in various tumor cell signaling pathways

🧠 How It Works
  • Tumors need blood vessels to grow and spread.
  • Lenvatinib blocks the signals that tumors use to create new blood vessels (angiogenesis).
  • It also inhibits growth signals that help cancer cells survive, multiply, and invade.
  • The result: tumor shrinkage or stabilization, and slower progression of disease.
⚑ Effect in Combination Therapies
When combined with pembrolizumab (in endometrial or other cancers), Lenvatinib’s anti-angiogenic effect enhances immune cell access to tumors, improving immunotherapy outcomes.
Β 

Dosage and Administration

πŸ’Š Letinib (Lenvatinib) is taken orally once daily and the dosage varies depending on the type of cancer, body weight, and whether it’s used alone or in combination with other medications.

πŸ“‹ General Administration Guidelines

  • Form: Oral capsules (4 mg and 10 mg)
  • Timing: Once daily, at the same time each day, with or without food
  • Swallow whole; do not crush or chew
  • If a dose is missed and it’s been <12 hours, take it; otherwise, skip it

πŸ”Ή Differentiated Thyroid Cancer (DTC)

  • Dose: 24 mg orally once daily
  • Until: Disease progression or unacceptable toxicity

πŸ”Ή Hepatocellular Carcinoma (HCC)

  • Dose:
    • β‰₯60 kg: 12 mg once daily
    • <60 kg: 8 mg once daily
  • Until: Disease progression or unacceptable toxicity

πŸ”ΉRenal Cell Carcinoma (RCC) – in combination with everolimus

  • Lenvatinib: 18 mg orally once daily
  • Everolimus: 5 mg orally once daily

πŸ”ΉEndometrial Carcinoma – in combination with pembrolizumab

  • Lenvatinib: 20 mg once daily
  • Pembrolizumab: 200 mg IV every 3 weeks OR 400 mg IV every 6 weeks

πŸ” Dose Modifications May Be Required For:

  • Hypertension
  • Proteinuria
  • Diarrhea
  • Liver/kidney dysfunction
  • Cardiac events
  • Dose may be reduced in steps (e.g., from 24 β†’ 20 β†’ 14 β†’ 10 β†’ 8 mg, etc.)

Common Side Effects

⚠️ Letinib (Lenvatinib) is effective but can cause a range of side effects, mostly related to its anti-angiogenic activity and multi-target kinase inhibition. Most are manageable with monitoring and supportive care.

Β 

🩺 Most Common Side Effects (>20%)

SystemSide Effect
GastrointestinalDiarrhea, nausea, vomiting, decreased appetite, abdominal pain
GeneralFatigue, weight loss
DermatologicHand-foot syndrome (palmar-plantar erythrodysesthesia), rash, dry skin
CardiovascularHypertension
RenalProteinuria
Endocrine/MetabolicHypothyroidism, hypertriglyceridemia
HematologicThrombocytopenia, anemia (less common)

πŸ’‘ Other Notable Side Effects

  • Stomatitis (mouth sores)
  • Hoarseness or voice changes (especially in thyroid cancer)
  • Delayed wound healing
  • Bleeding events (epistaxis, GI bleeding in rare cases)
  • Hepatotoxicity (elevated liver enzymes)

🚨 Serious (but less common) Side Effects

  • Cardiac dysfunction (e.g., heart failure)
  • Arterial thromboembolism (stroke, myocardial infarction)
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) – rare but serious
  • Gastrointestinal perforation or fistula formation

🧠 Patient Tip

If you experience severe headache, vision changes, confusion, or seizures, seek immediate medical helpβ€”these could be signs of RPLS or hypertensive crisis.

Monitoring

πŸ§ͺ LetinibΒ Regular monitoring is essential while taking Lenvatinib to detect and manage potential toxicities and ensure safe continuation of therapy.

πŸ“‹ Baseline Assessments (Before Starting Treatment)

  • Blood pressure
  • Liver function tests (LFTs)
  • Renal function (serum creatinine, urine protein)
  • Thyroid function (TSH, free T4)
  • Electrolytes (especially potassium, calcium, phosphate)
  • CBC with differential
  • Pregnancy test (if applicable)

πŸ”„ Ongoing Monitoring During Treatment

ParameterFrequencyWhy?
Blood pressureWeekly for first 2 months, then regularlyRisk of hypertension and complications
Liver function (ALT, AST, bilirubin)Every 2–4 weeks initially, then as neededRisk of hepatotoxicity
Renal function & urine proteinEvery 2–4 weeksDetect proteinuria and nephrotoxicity
TSH / thyroid functionEvery 4–6 weeksRisk of hypothyroidism
CBCEvery cycle or monthlyMonitor for cytopenias
ElectrolytesPeriodicallyEspecially with diarrhea or renal issues
Weight and appetiteOngoingMonitor for anorexia and weight loss

πŸ” Monitor for Specific Symptoms

  • Neurologic signs β†’ may indicate RPLS (headache, confusion, vision changes)
  • Signs of bleeding or GI perforation
  • Heart failure symptoms β†’ dyspnea, edema, fatigue
  • Skin or mucosal issues β†’ for hand-foot syndrome, stomatitis

🧠 Special Notes

  • Adjust or hold therapy for grade 3–4 toxicities
  • Dose reduction may be necessary for persistent moderate side effects
  • Drug interactions should also be monitored (especially with CYP3A modulators)

Precautions

⚠️ Letinib (Lenvatinib) is a powerful cancer therapy, but it requires careful use and patient monitoring due to the potential for serious side effects and drug interactions. Below are key precautions to consider before and during treatment:

🩺 Hypertension

  • Common and potentially severe
  • Control blood pressure before starting therapy
  • Monitor closely (especially in the first 2 months)
  • Withhold, reduce, or discontinue if hypertension is not manageable

🧠 Risk of Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

  • Watch for symptoms like headache, confusion, seizures, or vision changes
  • If suspected, stop Lenvatinib and confirm with imaging (e.g., MRI)

πŸ’” Cardiovascular Events

  • Increased risk of heart failure, myocardial infarction, arrhythmias
  • Use caution in patients with pre-existing cardiac conditions
  • Monitor EKG and ejection fraction if clinically indicated

🩸 Hemorrhagic Events

  • Includes epistaxis, GI bleeding, and rare cases of fatal hemorrhage
  • Avoid use in patients with active bleeding risks
  • Discontinue if severe or life-threatening bleeding occurs

🧫 Gastrointestinal Perforation and Fistulas

  • Rare but serious complication
  • Monitor for abdominal pain, signs of peritonitis, or GI bleeding
  • Use with caution in patients with a history of GI surgery or ulcers

πŸ§ͺ Hepatic and Renal Impairment

  • Adjust dose in moderate to severe liver/kidney dysfunction
  • Monitor LFTs and renal function regularly

βš–οΈ Thyroid Dysfunction

  • Can cause hypothyroidism or worsen pre-existing thyroid disease
  • Monitor TSH and free T4 regularly
  • May need thyroid hormone replacement

🚼 Pregnancy and Breastfeeding

  • Contraindicated in pregnancy – can cause fetal harm
  • Use effective contraception during treatment and for at least 30 days after the last dose
  • Do not breastfeed while on treatment and for at least 1 week after the final dose

πŸ”„ Wound Healing Impairment

  • Hold Lenvatinib at least 1 week before surgery and resume 2 weeks after, once healing is adequate

πŸ’Š Drug Interactions

  • Caution with CYP3A4 inducers/inhibitors, QT-prolonging agents, and antihypertensives
  • Regular medication reconciliation is essential

Drug Interactions

πŸ”„ LetinibΒ (Lenvatinib) is metabolized through non-CYP pathways (mainly by enzymatic and non-enzymatic hydrolysis), which means it has fewer CYP450-related interactions compared to many other cancer drugs. However, clinically significant interactions still exist and need attention.

πŸ’Š Key Drug Interaction Categories

πŸ”Ή Antihypertensive Agents

  • Lenvatinib commonly causes hypertension.
  • If the patient is on antihypertensives (e.g., ACE inhibitors, ARBs, beta-blockers), monitor closely and adjust doses as needed.
  • Avoid combinations with drugs that cause hypotension, as sudden BP drops can occur when lenvatinib is paused or dose-reduced.

πŸ”Ή CYP3A4 Inducers/Inhibitors

  • Lenvatinib is not primarily metabolized by CYP3A4, but caution is advised:
  • Inducers (e.g., rifampin, phenytoin, carbamazepine): may decrease lenvatinib exposure
  • Inhibitors (e.g., ketoconazole, clarithromycin): minimal effect, but still monitor for increased toxicity

πŸ”Ή QT-Prolonging Drugs

  • Lenvatinib may prolong the QT interval.
  • Use with caution alongside other QT-prolonging medications:
  • Antiarrhythmics (e.g., amiodarone, sotalol)
  • Certain antibiotics (e.g., levofloxacin, erythromycin)
  • Antipsychotics (e.g., haloperidol)
  • Monitor ECG and electrolytes if combining

πŸ”Ή Anticoagulants / Antiplatelets

  • Increased risk of bleeding when used with:
  • Warfarin
  • DOACs (e.g., apixaban, rivaroxaban)
  • NSAIDs
  • Monitor closely for signs of bleeding; consider dose adjustments or INR monitoring (if on warfarin)

πŸ”Ή Immunotherapy Agents

  • Often co-administered with pembrolizumab (e.g., in endometrial cancer)
  • No direct PK interaction, but watch for additive toxicities:
  • Liver toxicity
  • Fatigue
  • Immune-mediated side effects

πŸ”Ή Other TKIs or Targeted Therapies

  • Avoid co-administration with other VEGFR inhibitors or TKIs unless part of a protocol.
  • Increased risk of overlapping toxicities: hypertension, GI perforation, hepatic dysfunction.

βœ… Clinical Tips

  • Always review medication lists for hidden interactions.
  • Monitor blood pressure, liver function, ECGs, and bleeding signs when combining agents.
  • Use clinical judgment and multidisciplinary collaboration (e.g., pharmacist review).

Clinical Effectiveness

πŸ“ˆ Letinib (Lenvatinib) has demonstrated strong clinical effectiveness across multiple cancer types, particularly in thyroid, liver, kidney, and endometrial cancers. Its efficacy has been established through large, well-designed phase 3 clinical trials and has led to global regulatory approvals.

βœ… Differentiated Thyroid Cancer (DTC)

SELECT Trial (Phase 3)

  • Population: Patients with RAI-refractory DTC
  • Result:
    • Median Progression-Free Survival (PFS): 18.3 months (vs. 3.6 months with placebo)
    • Overall Response Rate (ORR): ~65%
    • Conclusion: Significant tumor shrinkage and disease stabilization

βœ… Hepatocellular Carcinoma (HCC)

REFLECT Trial (Phase 3)

  • Population: Unresectable HCC
  • Comparison: Lenvatinib vs. Sorafenib
  • Result:
    • Overall Survival (OS): 13.6 months (Lenvatinib) vs. 12.3 months (Sorafenib) – non-inferior
    • PFS: 7.4 months (Lenvatinib) vs. 3.7 months (Sorafenib)
    • ORR (by mRECIST): 40.6% (Lenvatinib) vs. 12.4% (Sorafenib)
    • Conclusion: Higher tumor response and better disease control

βœ… Renal Cell Carcinoma (RCC)

Combination with Everolimus (Phase 2 Trial)

  • Population: Patients with prior VEGF therapy
  • Result:
    • PFS: 14.6 months (combo) vs. 5.5 months (everolimus alone)
    • ORR: 43% (combo) vs. 6% (everolimus alone)
    • Conclusion: Significant improvement in tumor response and delay in progression

βœ… Endometrial Carcinoma

KEYNOTE-146 / Study 111 (Lenvatinib + Pembrolizumab)

  • Population: Advanced/recurrent endometrial cancer
  • Result:
    • ORR: ~38%
    • Median PFS: 7.4 months
    • Median OS: 16.7 months
    • Effective even in mismatch repair-proficient (pMMR) tumors, which typically respond poorly to immunotherapy alone

πŸ“Œ Key Points on Effectiveness

  • Rapid onset of tumor response in many cases
  • Works well in radioiodine-refractory thyroid cancers
  • Effective in first-line and second-line settings
  • Synergistic with immunotherapy agents like pembrolizumab

Tips for Patients

πŸ’‘Β TakingΒ LetinibΒ (Lenvatinib) can be effective in treating cancer, but it’s important for patients to follow certain guidelines to help maximize effectiveness while managing side effects. Here are some practical tips for patients:

βœ… Consistency is Key

  • Take Lenvatinib at the same time every day to help remember.
  • Swallow the capsule whole – do not crush, chew, or split it.
  • Do not skip doses, but if you miss one, take it if it’s less than 12 hours since your last dose. Otherwise, skip the missed dose and continue your usual schedule.

βœ… Manage Side Effects Actively

  • Fatigue & Weight Loss: Rest as needed and eat small, frequent meals to prevent weight loss.
  • Diarrhea & Nausea: Stay hydrated and try anti-nausea medications as recommended by your healthcare provider. Avoid spicy, greasy foods.
  • Hand-foot syndrome (redness or swelling on hands/feet): Apply moisturizers and avoid tight shoes. If it’s severe, inform your doctor as dose adjustments may be needed.

βœ… Monitor Blood Pressure Regularly

  • Lenvatinib can cause high blood pressure. Check your blood pressure regularly (especially in the first 2 months) and follow your doctor’s instructions for managing it.
  • If you have any dizziness or headaches, inform your healthcare provider, as this could be related to high blood pressure.

βœ… Report Symptoms of Serious Side Effects

  • RPLS (Reversible Posterior Leukoencephalopathy Syndrome): If you experience severe headaches, confusion, vision changes, or seizures, seek immediate medical attention.
  • GI issues: Notify your doctor if you experience abdominal pain, nausea, vomiting, or bloody stools.
  • Cardiac issues: Report any chest pain, difficulty breathing, or swelling in your legs.

βœ… Take Care of Your Skin

  • Lenvatinib can cause rash, dry skin, or sores. Use mild soap and moisturizing lotions. Wear sunscreen if you’re outdoors.
  • For hand-foot syndrome, avoid excessive friction or pressure on your hands and feet. Soak your hands/feet in warm water to ease discomfort.

βœ… Follow-up Appointments

  • Routine check-ups are essential: Ensure you attend all scheduled appointments for blood pressure checks, liver/kidney function tests, and thyroid function tests.
  • Adjustments to your dose may be necessary based on your side effects, so stay in regular contact with your healthcare team.

βœ… Pregnancy and Breastfeeding

  • Avoid pregnancy while on Lenvatinib and for at least 30 days after stopping treatment.
  • Do not breastfeed during treatment and for at least 1 week after your final dose.
  • Use reliable contraception to prevent pregnancy.

βœ… Diet and Lifestyle

  • Stay hydrated and eat a balanced diet. Lenvatinib may cause appetite loss, so eating small meals throughout the day may help.
  • Limit alcohol consumption as it may worsen certain side effects like liver toxicity.

βœ… Drug Interactions

  • Make sure your doctor is aware of all the medications (including over-the-counter drugs and supplements) you’re taking.
  • Avoid grapefruit and grapefruit juice as they may interact with Lenvatinib.