Concurrent Capecitabine and Radiotherapy for Rectal Cancer

Concurrent capecitabine (Xeloda) and radiotherapy is a neoadjuvant (preoperative) approach preferred particularly for locally advanced rectal cancer. The combination aims to shrink the tumor, improve surgical success, and achieve local control.

Treatment Goals

• Reduce tumor volume.
• Relieve symptoms such as bleeding, pain, and difficulty passing stools.
• Improve surgical resectability.
• Reduce local recurrence risk.
• Improve long-term disease-free and overall survival.

How Does This Treatment Work?

Capecitabine (https://www.drozdogan.com/kapesitabin-kapeda-xeloda-kapetabin-xeltabin-nedir-yan-etki/)

• Capecitabine is an initially inactive prodrug. It is enzymatically converted into 5-fluorouracil (5-FU) in the liver and particularly in tumor tissue. The resulting 5-FU acts in cancer cells in three main ways:
• Inhibiting DNA synthesis: 5-FU inhibits thymidylate synthase (TS), an enzyme essential for producing thymidine monophosphate (dTMP), which is required for DNA synthesis. TS inhibition disrupts DNA replication and leads to cell death.
• Disrupting RNA metabolism: 5-FU is incorporated into RNA in place of uridine triphosphate (UTP), producing nonfunctional RNA molecules and disrupting protein synthesis.
• Triggering apoptosis: Disrupted DNA and RNA synthesis arrests the cell cycle and triggers programmed cell death (apoptosis).

Radiotherapy

• DNA damage through ionizing radiation: Radiotherapy delivers high-energy ionizing radiation, usually X-rays, to cells, directly creating double-strand DNA breaks.
• Damage through free radicals: Radiation also ionizes water molecules, generating free radicals such as hydroxyl radicals (OH•). These damage DNA, proteins, and cell membranes through oxidation.
• Arresting the cell cycle: Cells unable to repair DNA damage are removed from the cell cycle, particularly at the G2/M phase, and directed toward apoptosis.

Combining capecitabine and radiotherapy stops DNA synthesis, disrupts RNA and protein production, and targets intracellular structures with ionizing radiation, creating a dual attack that increases cancer-cell death. This combination is highly effective for shrinking tumors and improving surgical success, particularly in localized tumors such as rectal cancer.

Administration and Dose

Capecitabine

• Dose: 825 mg/m² orally 2 times daily, in the morning and evening. (Total daily dose: 1650 mg/m²)
• Dosing schedule: Taken on radiotherapy days, usually 5 days a week, Monday–Friday. It is generally not given on weekends because radiotherapy is not administered.
• Treatment duration: Usually given with radiotherapy for 5–6 weeks.
• Timing: Take 30 minutes after meals (taking it with food increases absorption and reduces gastric toxicity).
• Tablet strengths: Capecitabine tablets are available as 150 mg and 500 mg strengths. The dose is adjusted to the patient's body surface area (BSA).

Radiotherapy

• Total dose: Usually 45–50.4 Gy in divided fractions.
• Dose per fraction: 1.8–2.0 Gy per day, 5 days a week (Monday–Friday)
• Total duration: Approximately 5–6 weeks
• Target area: Rectum and pelvic lymph nodes

Situations Requiring Attention

Kidney Dysfunction

• Capecitabine is excreted by the kidneys.
• Dose reduction or treatment delay may be needed when creatinine clearance is <50 mL/min.
• It is generally not used if clearance is <30 mL/min.

 Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia)

• May develop particularly after week 2 or 3.
• Symptoms: Redness, pain, and peeling on the palms and soles.
• Mild-to-moderate cases may improve with a dosing break.

Diarrhea and Dehydration

• Capecitabine and radiotherapy together may increase gastrointestinal toxicity.
• Severe diarrhea is managed with temporary treatment interruption, hydration, and antidiarrheal medication such as loperamide if needed.

 Mucositis (Inflammation of the Mouth and Intestinal Mucosa)

• Symptoms may include mouth sores and difficulty eating.
• Hygiene is very important; severe cases may require a treatment break.

Bone Marrow Suppression

• Although uncommon, capecitabine may cause leukopenia, neutropenia, or anemia.
• Blood counts should be monitored periodically during treatment.

Liver Dysfunction

• Liver function tests should be monitored.
• Use cautiously in severe liver dysfunction; dose adjustment may be needed.

Radiation Skin Reactions

• Redness, irritation, and peeling may occur in the treated area.
• Skin care, moisturizers, and avoiding extreme heat or cold are important.

Drug–Drug Interactions

• Concurrent use with warfarin (Coumadin), in particular, may increase INR.
• It may interact with antacids, folic acid supplements, and drugs such as phenytoin.

Pregnancy and Breastfeeding

• Both capecitabine and radiotherapy are teratogenic (carry a risk of birth defects).
• Pregnancy is strictly contraindicated. Breastfeeding is also not recommended.

Inadequate Nutrition

• Nutritional support may be needed because of loss of appetite, nausea, and gastrointestinal side effects during treatment.
• Dietitian support should be obtained if needed.

Side Effects

Clinical studies report the following most common side effects of capecitabine + radiotherapy for rectal cancer:

• Diarrhea [Grade 3-5] (7%)
• Radiotherapy skin rash [Grade 3-4] (3%)
• Anal pain [Grade 3] (3%)
• Tingling or numbness in the hands or feet [Grade 2-4] (2%)
• Dehydration [Grade 3] (2%)
• Fatigue [Grade 3] (2%)
• Nausea [Grade 3] (1%)
• Abdominal pain [Grade 3] (<1%)
• Hand-foot syndrome [Grade 3] (<1%)

People receiving capecitabine + radiotherapy do not all experience side effects in the same way. They may be mild in some patients and more severe in others. Everyone is different, and side effects can change over time. In some people, they may lead to treatment delays, dose reductions, or even discontinuation of a particular drug.

If you experience any side effects, please contact your doctor or nurse.