Clofarabine is a chemotherapy medication used to treat certain cancers. It belongs to a category of drugs known as purine nucleoside antimetabolites, which interfere with cell growth and division by mimicking natural body substances. Clofarabine is marketed as Clolar in the United States and Canada, and as Evoltra in Europe, Australia, and New Zealand.
Approved Medical Uses
Clofarabine is approved for pediatric patients (1 to 21 years old) with acute lymphoblastic leukemia (ALL). This targets cases where the leukemia has relapsed (returned after remission) or is refractory (not responded to at least two prior chemotherapy regimens).
While its main approved use is for pediatric ALL, clofarabine may also be explored off-label for other types of cancer. Research has investigated its potential effectiveness in conditions such as acute myeloid leukemia (AML) and juvenile myelomonocytic leukemia (JMML).
How Clofarabine Works Against Cancer
Clofarabine acts as a false building block, or analog, that cancer cells mistakenly incorporate into their genetic material. Once inside the cell, it transforms into its active form, clofarabine triphosphate. This active molecule then interferes with processes necessary for cancer cell survival and replication.
One primary way clofarabine works is by inhibiting DNA synthesis. It mimics natural purine nucleosides, components of DNA. When cancer cells try to replicate their DNA, they incorporate clofarabine triphosphate, which then causes the DNA replication process to stop prematurely.
Clofarabine also inhibits an enzyme called ribonucleotide reductase, responsible for producing deoxyribonucleotides, the fundamental building blocks of DNA. By blocking this enzyme, clofarabine depletes the supply of these essential building blocks, further hindering the cancer cells’ ability to create new DNA and multiply. Clofarabine can also disrupt the function and integrity of mitochondria, the energy-producing parts of the cell, triggering programmed cell death, known as apoptosis.
Treatment Protocol and Patient Monitoring
Clofarabine is administered as an intravenous (IV) infusion, delivered directly into a vein. Each infusion typically lasts about two hours and is given once daily for five consecutive days.
This five-day period constitutes one treatment cycle. Depending on how well the patient recovers and responds to the medication, these cycles may be repeated every 2 to 6 weeks. Throughout the treatment, patients undergo careful monitoring to assess response and manage potential effects.
Regular blood tests are conducted frequently, including complete blood counts, to check for bone marrow suppression. These tests evaluate red blood cells, white blood cells, and platelets. Monitoring of liver and kidney function is also a routine part of the protocol, as these organs can be affected by the drug. Maintaining proper hydration is also an important part of the treatment plan, as it helps to prevent certain complications.
Potential Side Effects and Complications
Common side effects of clofarabine include nausea, vomiting, diarrhea, general fatigue, headache, skin rash, itching, fever, and chills. Some individuals may also report stomach pain, a loss of appetite, discomfort in their arms or legs, low blood pressure, or nosebleeds.
One significant concern is severe bone marrow suppression, which can lead to reduced levels of all types of blood cells. Anemia, a low red blood cell count, can cause tiredness, weakness, pale skin, and shortness of breath. Neutropenia, a reduction in white blood cells (specifically neutrophils), increases the susceptibility to infections, often presenting with fever. Thrombocytopenia, characterized by low platelet counts, can result in easy bruising, prolonged bleeding from minor cuts, or the appearance of small red or purple spots on the skin. Recovery of platelet counts after treatment can sometimes take an extended period.
A less common but serious complication is capillary leak syndrome (CLS), where fluid and proteins leak from small blood vessels into surrounding tissues. This can cause widespread swelling, a sudden drop in blood pressure, a rapid heart rate, and rapid breathing. CLS can progress to involve organ damage, particularly to the lungs and kidneys. This condition is often associated with a systemic inflammatory response.
Tumor lysis syndrome (TLS) is another serious potential complication, occurring when a large number of cancer cells break down rapidly. This process releases their internal contents, such as potassium, phosphate, and uric acid, into the bloodstream. High levels of uric acid can harm the kidneys, while elevated potassium can lead to irregular heart rhythms. Imbalances in phosphate and calcium can also occur, potentially causing muscle spasms or seizures.
Liver and kidney toxicity can also develop. Liver-related effects may include elevated liver enzymes, indicating stress on the organ, and in some cases, jaundice, which is a yellowing of the skin or eyes. For the kidneys, there can be an increase in creatinine levels, suggesting reduced kidney function, and in some instances, acute kidney failure has been reported. Patients are closely monitored for these potential issues.