Capecitabine (brand name Xeloda) is an oral chemotherapy medication used to treat various solid tumors, including metastatic colorectal, breast, and gastric cancers. It is a prodrug, meaning it is inactive when taken but converts into the potent anti-cancer agent 5-fluorouracil (5-FU) inside the body. This conversion is designed to be tumor-selective, aiming for higher concentrations of the active drug directly within cancerous tissue. Determining the correct dosage is a careful process, relying on patient-specific factors to balance effective treatment against the risk of side effects.
Principles of Initial Dosage Determination
The initial dose of capecitabine is calculated using the patient’s Body Surface Area (BSA), which is a measurement derived from a person’s weight and height. This method is employed to personalize the treatment, as it accounts for differences in body size that can influence how a drug is distributed and cleared from the body. By calculating the dose based on square meters of body surface (\(\text{mg/m}^2\)), oncologists attempt to achieve a consistent drug exposure level across different individuals.
The standard starting dosage rate, expressed in milligrams per square meter per day (\(\text{mg/m}^2/\text{day}\)), varies significantly depending on the specific type of cancer being treated and whether capecitabine is used alone or in combination with other drugs. For example, when used as a single agent for adjuvant treatment of colon cancer or monotherapy for metastatic breast cancer, the typical initial dose is \(1250\ \text{mg/m}^2\) taken twice daily for the first two weeks of a cycle. This results in a total daily dose of \(2500\ \text{mg/m}^2\).
However, when capecitabine is used in combination regimens or with radiation therapy, the initial dose is often lower to accommodate the added toxicity of the concurrent treatments. For instance, in combination with oxaliplatin for metastatic colorectal cancer, the starting dose might be reduced to \(1000\ \text{mg/m}^2\) twice daily. A further reduction to \(825\ \text{mg/m}^2\) twice daily is common when the drug is given alongside radiation therapy for rectal cancer. These lower starting doses are chosen to maintain a therapeutic effect while mitigating the cumulative side effects that occur with multi-agent therapy.
Common Treatment Schedules and Cycles
Capecitabine is typically administered using a repeating, intermittent schedule, most commonly structured around a 3-week cycle. Within this standard cycle, the patient takes the medication twice daily for 14 consecutive days, followed by a 7-day rest period where no drug is taken. Patients are usually instructed to take the tablets approximately 12 hours apart, ensuring they are taken within 30 minutes after a meal to optimize absorption and reduce stomach upset.
The 7-day rest period is an important part of the treatment schedule. This pause allows the patient’s normal, rapidly dividing cells—such as those lining the gastrointestinal tract and bone marrow—to recover from the chemotherapy effects. This recovery phase reduces the risk and severity of common side effects like diarrhea, nausea, and low blood counts, helping maintain adherence to the treatment plan.
The total duration of therapy is determined by the treatment setting and the patient’s response to the drug. For adjuvant treatment, such as after surgery for colon cancer, capecitabine is often given for a fixed period, typically for a total of eight 3-week cycles, or 24 weeks. For advanced or metastatic disease, the treatment often continues until the cancer progresses or the patient experiences side effects that are no longer manageable.
Necessary Dose Modifications
The dosage prescribed at the start of treatment is not fixed and frequently requires adjustment based on how the patient tolerates the medication. One of the primary reasons for modifying the dose is the management of adverse reactions, which is a process known as toxicity management. The severity of side effects is graded on a scale, and the higher the grade, the more likely a dose change is mandated.
A common dose-limiting side effect is Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia), involving redness, swelling, and pain on the palms and soles. If a patient experiences moderate (Grade 2) toxicity, the oncologist typically interrupts treatment until the side effect resolves. For a first occurrence of severe (Grade 3) toxicity, the drug is stopped until the toxicity improves, and the subsequent dose is reduced, often to 75% of the starting amount.
Dose modifications are also required to accommodate a patient’s compromised organ function, particularly in the kidneys. Capecitabine and its metabolites are primarily cleared from the body by the kidneys, so poor renal function can lead to a buildup of the drug, increasing the risk of severe toxicity. For patients with moderate kidney impairment, a mandatory reduction to 75% of the recommended starting dose is necessary.
The drug is not used in patients with severe renal impairment due to the significant risk of toxicity. If the dose is reduced due to toxicity, it should not be increased again later. These adjustments are a dynamic part of the treatment plan, strictly managed by the oncology team to ensure efficacy and patient safety.