Capecitabine

Capecitabine is a medication designed to transform into five fluorouracil (5 FU) once it enters the body. It serves as a chemotherapy agent primarily used in the field of oncology. What sets it apart is that it can be taken orally, which differs from the method of administering chemotherapy through intravenous treatments.

Capecitabine, which was introduced in the 1990s came about in response to the demand for chemotherapy treatments that are more convenient for patients. As healthcare providers aimed to reduce hospital stays and improve the patient journey, the introduction of oral medications like Capecitabine significantly changed cancer treatment. It gave patients the freedom to undergo chemotherapy in the comfort of their homes, granting them more control, over their treatment process.

Capecitabine has brought about changes in the field of oncology treatment. Its ability to be taken orally, its effectiveness comparable to chemotherapy agents, and its flexibility in treatment scheduling have solidified its position in various therapeutic regimens. This further emphasizes its role in the arsenal of oncologists.

After conducting clinical trials and extensive research, the FDA has approved capecitabine for the treatment of certain types of cancer¹². It is considered an option for colorectal cancer patients following surgery or in cases where metastasis has occurred¹²³. Additionally, it benefits breast cancer patients, particularly when anthracycline-based treatment plans cannot be used¹²⁴. In stages of gastric cancer, it is often used alongside other medications to enhance its effectiveness³. Capecitabine is an oral chemotherapy drug that belongs to the class of antimetabolites and works by interfering with the synthesis of DNA and RNA in cancer cells⁴.

References:

1: FDA Approves Capecitabine, First Oral Chemotherapy for Treatment of Metastatic Colorectal Cancer | Cancer Network 2: First Generic Version of Capecitabine Gains FDA Approval - OncLive 3: FDA approves updated drug labeling including new indications and dosing regimens for capecitabine | FDA 4: Capecitabine - National Cancer Institute

Apart from its approved applications by the FDA, capecitabine provides a range of advantages. These benefits include visits to the hospital, a manageable profile of side effects, and the ability to personalize dosage based on each patient’s specific needs¹²³. Capecitabine is an oral chemotherapy drug that can be taken at home, reducing the need for hospital visits and intravenous administration¹². It also has few side effects in many people and can control cases of advanced breast cancer, sometimes for long periods¹⁴. The capecitabine dosage can be adjusted according to the patient’s body surface area, renal function, and tolerance²³.

References:

1: Capecitabine (Xeloda) | Cancer information | Cancer Research UK 2: Capecitabine (Oral Route) - Mayo Clinic 3: Capecitabine - National Cancer Institute 4: Benefits of capecitabine in hormone receptor-positive compared with hormone receptor-negative breast cancer | Cochrane

Capecitabine, a prodrug, goes through enzymatic changes in the liver and tumor tissues, transforming into its active state called 5 FU. This particular compound hinders the synthesis of DNA, effectively preventing the growth of cancer cells.

Its brilliance lies in its ability to target cells. While 5 FU undoubtedly harms cancer cells, it has a lower impact on healthy cells resulting in fewer overall side effects.

Once 5 FU is produced, it becomes a part of the RNA and DNA within cancer cells. This integration causes disturbance in cellular processes, ultimately resulting in programmed cell death, also known as apoptosis. Furthermore, 5 FU hinders the activity of thymidylate synthase, an enzyme that plays a role in DNA synthesis and repair.

The dosage required may differ depending on the type of cancer being treated and the patient's individual characteristics. In general, for cancer, a dose of 1250 mg/m² is recommended to be taken twice daily. A similar dosage of 1250 mg/m² for breast cancer is also advised daily. For cancer, the recommended dosage is 1000 mg/m² to be taken twice daily. It's important to note that adjustments might be necessary based on factors such as function side effects observed and other medications being taken concurrently.

It is generally recommended to take this medication by mouth with water within 30 minutes after eating a meal. This helps to ensure absorption and reduces the likelihood of experiencing any discomfort in the stomach or intestines.

Following the instructions is crucial to ensure that Capecitabine is effective in its therapeutic purposes while minimizing undesired side effects. Taking much of the medication can worsen toxicity, whereas taking too little may potentially impact the success of the treatment.

Capecitabine is classified as an ester in its chemical description, specifically known as 5' deoxy five fluoros N [(benzyloxy)carbonyl] cytidine. It has the formula C15H22FN3O6 and exhibits distinct optical and physiochemical characteristics contributing to its pharmacological effects.

The main component is Capecitabine, which's the active ingredient. Other substances, such as microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, and magnesium stearate, are typically included to aid in shaping and optimizing the tablet's performance.

Usually, you can find tablets in two strengths; 150 mg and 500 mg. This variety allows for flexibility in meeting dosage needs.

Some common symptoms of this condition include feeling sick, throwing up, experiencing stomach upset, and having a decreased desire to eat. In some cases, patients may need medications to help alleviate these symptoms.

Patients need to differentiate between fatigue that can be managed and weakness that is severe enough to require attention.

Also known as palmar erythrodysesthesia, this condition involves the hands and feet becoming red, painful, and potentially developing blisters.

It is important to monitor liver function while taking Capecitabine as it can occasionally hurt liver health.

The range of side effects can vary, from alopecia or hair thinning to more severe ones like neutropenia, a significant decrease in white blood cells. It is crucial to prioritize monitoring and education.

Possible side effects of the treatment include heart-related symptoms, severe skin reactions, and a significant weakening of the system. Although these occurrences are rare, they can still happen occasionally.

Although Capecitabine's immediate side effects are usually controllable, it is essential to monitor for potential long-term effects such as cumulative neuropathy.

Using Capecitabine for purposes than those approved by the FDA typically relying on anecdotal evidence or initial research is known as, off label use.

Recent studies suggest that capecitabine has shown effectiveness in treating cancers such as pancreatic cancer and hepatocellular carcinoma¹²³. Capecitabine is an oral chemotherapy drug that can be used as a second-line treatment after sorafenib failure or in combination with other drugs for advanced liver cancer¹³. It has also been reported to induce a sustained complete response in a patient with metastatic pancreatic cancer².

References:

1: Systemic treatment for advanced hepatocellular carcinoma - UpToDate 2: Sustained complete response of advanced hepatocellular carcinoma with metronomic capecitabine after sorafenib failure: a case report | Cancer Communications | Full Text 3: Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation - SpringerLink

There have been a number of phase II trials and retrospective analyses that highlight the potential of capecitabine in these areas¹²³. However, we are still awaiting phase III studies to draw definitive conclusions. Phase III studies are more extensive and more rigorous than phase II studies and can provide more reliable evidence of the efficacy and safety of capecitabine in different cancer settings.

References:

1: Benefits of capecitabine in hormone receptor-positive compared with hormone receptor-negative breast cancer | Cochrane 2: Metronomic capecitabine as second-line treatment for hepatocellular carcinoma after sorafenib discontinuation - SpringerLink 3: Capecitabine monotherapy in advanced biliary tract cancer: A single-center retrospective analysis - ScienceDirect : Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs No Maintenance Therapy on Disease-Free Survival Among Patients With Triple-Negative Breast Cancer Who Had Received Standard Adjuvant Chemotherapy: The SYSUCC-001 Randomized Clinical Trial | Breast Cancer | JAMA | JAMA Network : Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial - The Lancet : Effect of Capecitabine Maintenance Therapy Plus Best Supportive Care vs Best Supportive Care Alone on Progression-Free Survival Among Patients With Newly Diagnosed Metastatic Nasopharyngeal Carcinoma Who Had Received Induction Chemotherapy: A Phase 3 Randomized Clinical Trial | Oncology | JAMA Oncology | JAMA Network

The effectiveness of Capecitabine may be affected when used together with anticoagulants, specific antivirals, or other chemotherapeutic agents due to changes in its pharmacokinetics.

Taking calcium or iron-rich diets could potentially hinder the absorption of Capecitabine. Therefore it is recommended to take this medication after having a meal.

Establishing communication channels, with healthcare providers conducting regular reviews of medications and providing comprehensive patient education, play a crucial role in preventing harmful interactions.

Patients with kidney problems, a history of allergic reactions to Capecitabine or 5 FU, and those currently undergoing treatment with certain antiviral medications should not take this medication due to potential risks.

If you experience any symptoms, particularly extreme tiredness, heart palpitations, or allergic reactions, you must stop the treatment immediately and seek medical assistance.

Patients with a kidney condition or are known to be allergic to Capecitabine or fluoropyrimidine should avoid using it. Furthermore, individuals with a confirmed deficiency of dihydropyrimidine dehydrogenase (DPD) are more susceptible to harmful effects.

Concomitant use of medications like sorivudine or similar drugs is not recommended because it may increase the risk of side effects. Blood thinners; There is a higher chance of bleeding. Antifungal medications; It could lead to higher levels of Capecitabine in the bloodstream.

Patients with kidney problems or a history of heart disease should be cautious when considering using Capecitabine. It is essential to exercise caution if there is a history of liver disease or if the patient is currently receiving chemotherapy drugs.

Regular blood count examinations, liver function evaluations, and eyeing for hand-foot syndrome are essential. Assessing the heart health of individuals with pre-existing heart conditions might be necessary.

To ensure the safety and effectiveness of therapy, it is essential to conduct an evaluation before starting. This evaluation includes tests for liver function a blood count, and a cardiac evaluation for individuals who may be, at risk.

Patients should make sure to limit their exposure to the sun, stay properly hydrated, be mindful of their alcohol intake, and avoid using, over-the-counter medications without consulting a physician.

Elderly individuals might require adjustments to their medication dosage because of changes in how their bodies process drugs or health conditions they may have. It is often wise to start with a dose and closely monitor their response.

Age-related kidney problems or increased vulnerability may increase the chances of experiencing side effects. It is crucial to be vigilant for any signs of heart-related issues in this specific population.

Capecitabine may have effects on unborn babies if given to pregnant women. It is recommended that women who can get use reliable birth control methods while undergoing treatment and for a certain period after treatment.

It is unclear whether Capecitabine or its byproducts are eliminated in breast milk. Due to the possibility of adverse effects on breastfeeding infants, it is advised to carefully consider stopping breastfeeding or avoiding this medication, taking into account its significance to the mother.

The use of Capecitabine in patients has not been thoroughly studied for its safety and effectiveness. If it is being considered for off-label use, it is essential to monitor and assess the patient's condition regularly.

Determining the dosage for children is still unclear. Before making any decisions, assessing the risks and benefits involved is crucial.

Excessive use can lead to neurotoxicity, cardiotoxicity, and gastrointestinal issues. Quickly identifying and intervening can help mitigate the severity of these consequences.

The first thing to do is to stop taking Capecitabine away. We can then provide treatment and support the patient with intravenous fluids and medication to prevent nausea. In some cases, it may be necessary for the patient to be admitted to the hospital.

Store capecitabine at room temperature, between 20°C and 25°C (68°F to 77°F). It is acceptable to expose it to temperatures ranging from 15°C to 30°C (59°F to 86°F).

The expiration dates, usually printed on the packaging, show how the product will remain stable. After the expiration date, the medication may lose its effectiveness or safety. It is not recommended to consume it.

It is essential to avoid disposing of expired tablets through wastewater or regular household waste. Checking regulations for proper disposal methods that prioritize environmental protection is recommended.

Pharmacists and technicians should always wear gloves while dispensing medications. It is essential to avoid any contact with crushed or broken tablets.

Wearing protective gloves when handling the drug and avoiding direct contact with it is essential. After conducting, make sure to wash your hands. If you accidentally get the dope on your skin or in your eyes, it's recommended to rinse with a lot of water.