Cabozantinib Caboxen 20mg

Product Name: Caboxen

Generic Name: Cabozantinib

Dosage Form: Capsules

Specification: 20 mg/capsule; 90 capsules/bottle

Manufacturer: Everest Medicines

Cabozantinib is a multi-targeted, broad-spectrum anticancer drug capable of inhibiting at least nine distinct targets, including MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, and KIT.

Currently, Cabozantinib has demonstrated significant therapeutic efficacy across a wide range of solid tumors—including kidney cancer, thyroid cancer, liver cancer, soft tissue sarcoma, non-small cell lung cancer, prostate cancer, breast cancer, ovarian cancer, and colorectal cancer—with particularly outstanding results in controlling bone metastases. Due to its broad effectiveness against multiple cancer types, Cabozantinib is often referred to as the "universal remedy" among targeted therapies, possessing broad-spectrum anticancer capabilities.

Treatment of Renal Cell Carcinoma: The response rate of Cabozantinib is several times higher than that of Sutent (46% vs. 18%), and it significantly extends overall survival (30.3 months vs. 21.8 months). The side effect profiles of both drugs are very similar, with adverse event rates of 67% and 68%, respectively. The primary side effects include diarrhea, fatigue, hypertension, and hand-foot syndrome. Currently, Cabozantinib has become a preferred first-line treatment option for advanced kidney cancer.

Treatment of Hepatocellular Carcinoma: In patients with advanced liver cancer treated with Cabozantinib, overall survival was significantly prolonged, and the risk of mortality was reduced by 37%. The objective response rate was approximately 5%. Currently, alongside drugs such as Regorafenib and PD-1 antibodies, Cabozantinib has established itself as a key therapeutic agent for advanced liver cancer.

Treatment of Lung Cancer: Among patients with non-small cell lung cancer (NSCLC), approximately 2% harbor RET gene rearrangements. These patients are eligible for treatment with Cabozantinib. In 2016, the prestigious medical journal *The Lancet Oncology* published clinical trial data regarding the use of Cabozantinib in lung cancer patients with RET rearrangements: in a cohort of 26 patients, the objective response rate was 28%, and the tumor control rate approached 100%. Furthermore, for lung cancer patients with EGFR wild-type tumors who have failed first-line therapy, treatment with Cabozantinib in combination with Tarceva (Erlotinib) resulted in a significantly longer survival duration compared to either agent used alone. The median survival in the combination therapy group was 13.3 months, compared to 9.2 months in the Cabozantinib monotherapy group and 5.1 months in the Tarceva monotherapy group.

Treatment of Thyroid Cancer: For thyroid cancer patients harboring *RET* mutations, Cabozantinib significantly extended overall survival, increasing it from 18.9 months to 44.3 months—more than a twofold increase. In the overall patient population, overall survival also improved from 21.1 months to 26.6 months.

Cabozantinib targets a multitude of molecular pathways; some of these targets are implicated in the formation of bone metastases. Consequently, the drug demonstrates excellent efficacy in controlling bone metastases associated with solid tumors and has been widely adopted for the treatment of bone metastases in patients with renal cell carcinoma and prostate cancer.

Cabozantinib can enhance the efficacy of immunotherapies—such as PD-1 antibodies—by mechanisms that include eliminating "myeloid-derived suppressor cells" (MDSCs) located within the tumor microenvironment, which otherwise act to facilitate tumor growth. As a result, numerous studies have identified Cabozantinib as an "ideal partner" for PD-1 antibodies in combination therapy regimens, yielding favorable clinical outcomes.

In 2012, the U.S. FDA approved Cabozantinib capsules (140 mg/day) for the treatment of progressive, metastatic medullary thyroid carcinoma (MTC). Subsequently, in April 2016, the FDA approved Cabozantinib tablets (60 mg/day) for the treatment of advanced renal cell carcinoma (RCC) in patients who had previously received anti-angiogenic therapy.

In January 2019, the U.S. FDA approved Cabozantinib tablets (60 mg/day) for the treatment of advanced hepatocellular carcinoma (HCC) in patients whose disease had progressed following treatment with other standard systemic therapies, such as Lenvatinib or Sorafenib.

As a second-line therapeutic agent for liver cancer, Cabozantinib tablets can significantly prolong survival in patients with HCC, reducing the risk of death or disease progression by 56%. The prognosis for patients with advanced liver cancer is often poor, and treatment options become limited after receiving systemic therapy. The CELESTIAL trial demonstrated that Cabozantinib tablets significantly improved overall survival in patients with advanced liver cancer; progression-free survival and objective response rates also saw significant improvements, establishing it as a new treatment option for liver cancer patients.

China has a vast population of liver cancer patients, accounting for over 50% of all newly diagnosed cases globally each year. Among these cases, liver cancer caused by Hepatitis B is the most prevalent. Due to the insidious nature of the disease, most liver cancer cases are already in an advanced stage by the time they are detected. The approval of Cabozantinib tablets for the treatment of liver cancer brings new hope to patients in China.

To ensure medication safety, please exercise caution when making your choice!

Indications:

Cabozantinib has a broad range of indications, primarily including:

(1) Advanced renal cell carcinoma (kidney cancer) in patients who have previously received anti-angiogenic therapy;

(2) Medullary thyroid carcinoma that is not amenable to surgical resection;

(3) Liver cancer in patients who have developed resistance to Sorafenib (Nexavar);

(4) Advanced prostate cancer in patients with bone metastases.

Usage and Dosage:

According to pharmacokinetic studies conducted in Japanese populations, the previously recommended dosages of Cabozantinib—100 mg, 125 mg, or 140 mg—were found to be significantly higher than necessary, resulting in a higher incidence of side effects.

So, how should patients adjust their starting dosage? The following dosage adjustment guidelines are suggested for consideration:

(1) For Cabozantinib monotherapy, the recommended starting dosage is 40 mg. Generally, drug levels reach a steady-state peak after two weeks; at this point, any potential side effects may become more pronounced.

(2) Dosage increases should be considered only after two weeks of treatment, provided the patient demonstrates good tolerability. Increases should be gradual; raising the dosage to 60 mg is a reasonable next step.

(3) The maximum dosage for monotherapy is generally considered to be 80 mg. This increase may be considered after two weeks (or a longer period) if the patient remains free of significant side effects and if the tumor has shrunk or a clear therapeutic effect is observed.

(4) For patients undergoing combination therapy, it is recommended to start with a Cabozantinib dosage of 40 mg, and to consider increasing the dosage only after two weeks of treatment. For patients with bone metastases undergoing combination therapy, if Cabozantinib-related side effects are significant, a dose reduction to 20 mg may be considered.

(5) Cabozantinib can induce hypomagnesemia and symptoms of hypothyroidism. If significant side effects occur during treatment, consider monitoring serum electrolytes and the five-panel thyroid function tests. If hypothyroidism is detected, oral thyroxine supplementation may be administered; if hypomagnesemia is detected, oral potassium-magnesium aspartate supplementation may be used.

Cabozantinib should be taken at least one hour before or two hours after a meal—that is, on an empty stomach. Since Cabozantinib is a CYP3A4 substrate, the consumption of grapefruit should be avoided during treatment, as this can increase systemic drug concentrations and potentially lead to severe adverse reactions.

Close monitoring is essential during treatment. Parameters requiring periodic monitoring include urine protein levels, liver function, complete blood count (CBC) with differential and platelet count, serum electrolytes, blood pressure, and signs or symptoms of bleeding. Cabozantinib treatment should be discontinued if nephrotic syndrome or Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurs.

(6) Must not be taken with food;

(7) Do not consume food for at least one hour before taking the medication and for at least one hour after taking it—maintaining a food-free interval of at least two hours in total;

(8) In the event of adverse reactions, dose reduction or temporary interruption of treatment may be considered.

Common side effects include: diarrhea, nausea, vomiting, constipation, oral mucositis (mouth sores), epistaxis (nosebleeds), decreased appetite, etc.

Product Specifications

Product Name: Cabozantinib 20 mg Capsules (90-count) — Everest Caboxen 20 mg

Common Name: Cabozantinib

Active Ingredient: Cabozantinib

Dosage Form: Capsules

Specification: 20 mg × 90 capsules per box

Manufacturer: Everest Pharmaceuticals

Indications/Applications: Cabozantinib was developed by the U.S. pharmaceutical company Exelixis. Compared to other targeted therapies—such as Imatinib or Gefitinib—Cabozantinib targets a broader spectrum of molecular pathways. To date, the approved indications for Cabozantinib include medullary thyroid carcinoma, advanced renal cell carcinoma, lung cancer, and hepatocellular carcinoma (liver cancer). Furthermore, Cabozantinib is also utilized in the management of bone metastases associated with various solid tumors, such as prostate cancer.

Cabozantinib is a multi-targeted, broad-spectrum anticancer agent capable of inhibiting at least nine distinct targets, including MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, and KIT.

Dosage and Administration: Based on pharmacokinetic studies conducted in Japanese populations, the previously recommended Cabozantinib dosages—typically 100 mg, 125 mg, or 140 mg—were found to be significantly higher than necessary, resulting in a correspondingly higher incidence of side effects. Consequently, how should patients adjust their initial starting dosage? The following dosage adjustment guidelines are recommended for consideration:

(1) For Cabozantinib monotherapy, the recommended starting dose is 40 mg. Generally, drug concentrations reach a steady-state peak after two weeks of administration; at this juncture, any potential side effects may become more pronounced.

(2) An increase in dosage should only be considered after two weeks of treatment, provided the patient demonstrates good tolerability. Dosage increases should be gradual; an increase to 60 mg may be considered.

(3) The maximum recommended dosage for monotherapy is 80 mg. This increase may be considered if, after two weeks or a longer period of treatment, the patient remains free of significant side effects and demonstrates evidence of tumor shrinkage or other clinically meaningful therapeutic benefits.

(4) For patients undergoing combination therapy, the recommended starting dose of Cabozantinib is 40 mg, with dosage adjustments to be considered after two weeks of treatment. Specifically for patients with bone metastases receiving combination therapy, if Cabozantinib-related side effects prove to be severe or intolerable, a dosage reduction to 20 mg may be considered.

(5) Cabozantinib is known to induce hypomagnesemia and symptoms of hypothyroidism. If significant side effects occur during treatment, it is advisable to monitor serum electrolyte levels and thyroid function (specifically the five-panel thyroid test). Should hypothyroidism be detected, oral thyroid hormone replacement therapy may be initiated; in cases of hypomagnesemia, oral potassium-magnesium aspartate supplementation may be administered.

Cabozantinib should be taken at least one hour before or two hours after a meal—that is, on an empty stomach. As Cabozantinib is a substrate of the CYP3A4 enzyme, patients should strictly avoid consuming grapefruit or grapefruit products during treatment, as this can lead to elevated plasma drug concentrations and, consequently, an increased risk of severe adverse reactions. Appropriate monitoring should be conducted during treatment. Parameters requiring periodic monitoring include urine protein, liver function, CBC with differential and platelets, serum electrolytes, blood pressure, and signs or symptoms of bleeding. Cabozantinib treatment should be discontinued if nephrotic syndrome or Reversible Posterior Leukoencephalopathy Syndrome (RPLS) occurs.