Clofarabine

Clofarabine (marketed as Clolar) is a prescription drug used for the treatment of acute lymphoblastic leukemia (ALL), a type of blood cancer. It is indicated for relapsed leukemia or leukemia that is refractive to other treatment. Clofarabine belongs to a family of anti-cancer and anti-viral drugs called nucleoside analogs. Other members of this family used as cancer chemotherapy are vidarabine and cytarabine.

Clolar is marketed by Genzyme. FDA approval was granted in December of 2004.

Uses

Clolar is specifically indicated for the treatment of patients one to 21 years of age with relapsed or refractory acute lymphoblastic leukemia (ALL) after at least two prior regimens.

How Clofarabine is Taken

The recommended dosage is 52 mg/m² (based on the patient's estimated body surface area) administered by intravenous (IV) infusion for two hours daily for five consecutive days.

This treatment cycle is repeated following recovery or return to baseline organ function, approximately every two to six weeks.

How It Works

Clofarabine acts through several mechanisms to kill cancer and other rapidly dividing cells in the body:

• Clofarabine inhibits DNA synthesis by inhibiting an enzyme called ribonucleotide reductase.

• It also terminates DNA chain elongation and inhibits DNA repair through incorporation into the elongating DNA chain.

• Clofarabine also disrupts the integrity of mitochondrial membrane, leading to the release of certain mitochondrial proteins (cytochrome C and apoptosis-inducing factor) that leads to cell death.

How the Body Affects Clofarabine

Based on studies, 49-60% of the original dose of clofarabine is excreted in the urine unchanged. ^[1]

Benefits

Clofarabine has been shown to be effective as a treatment for refractory acute lymphocytic leukemia in children. One study showed a 30% response rate to treatment. ^[2]

Side Effects

The most common side effects associated with Clofarabine are:

• Vomiting
• Nausea
• Diarrhea
• Anemia (low red blood cell and/or hemoglobin counts)
• Leukopenia or Neutropenia (low white blood cell count)
• Thrombocytopenia (low blood platelet count)
• Infection

Risks

Complications

Suppression of bone marrow function should be anticipated. This is usually reversible and appears to be dose dependent. The bone marrow suppression may present as neutropenia (low number of white blood cells), thrombocytopenia (low platelets), and anemia (low red blood cell count).

Clofarabine may cause fetal harm when administered to a pregnant woman. Female patients should be advised to use effective contraceptive measures to prevent pregnancy and, if already with child, to avoid breast feeding during treatment with Clolar.

Interactions

There are no known clinically significant interactions of clofarabine with other drugs.

Clinical Trials

Click the following link to see clinical trials currently recruiting patients: Clofarabine clinical trials

Research

The following are recently completed studies: ^[3]

• The dosing and efficacy of combining clofarabine and Ara-C (another chemotherapeutic agent) to treat acute myelocytic leukemia (AML) and myelodysplastic syndrome (MDS). ^[4]
• The use of clofarabine for treatment of AML in older patients (greater than 60 years of age). ^[5]
• The use of oral clofarabine in the treatment of solid tumors refractory to other treatment. ^[6]
• The use of clofarabine to treat Chronic Lymphocytic Leukemia (CLL) and Acute Myelocytic Leukemia.

References

1. ↑ U.S. Food and Drug Administration web site. Clolar for Intravenous Infusion.
2. ↑ Jeha S, Gaynon PS, Razzouk BI. Phase II study of clofarabine in pediatric patients with refractory or relapsed acute lymphoblastic leukemia. J Clin Oncol. 2006 Apr 20;24(12):1917-23. Abstract
3. ↑ Clofarabine. Drugs R D. 2004;5(4):213-7. Abstract
4. ↑ ClinicalTrials.gov web site. Clofarabine vs Clofarabine in Plus With Low-Dose Ara-C in Previously Untreated Patients With AML and High-Risk MDS.
5. ↑ ClinicalTrials.gov web site. A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia
6. ↑ Kantarjian HM, Gandhi V, Kozuch P, et al. Phase I clinical pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol. 2003 Mar 15;21(6):1167-73. Abstract | Full Text

External Links

U.S. Food and Drug Administration: Patient Information Sheet

National Cancer Institute: Clofarabine