The MDS Beacon™

Clolar (clofarabine) may be effective in the treatment of high-risk myelodysplastic syndromes (MDS), according to a recent article reviewing studies of Clolar in the treatment of leukemia and related conditions.

The article, which was published in the journal Expert Opinion on Investigational Drugs, summarized current developments in the study of Clolar, especially for elderly acute myeloid leukemia (AML) patients. Summaries of several studies involving the use of Clolar in MDS patients were also included.

Clolar works by inhibiting DNA synthesis, which in turn interferes with the growth of tumor cells. It is currently approved in the United States for pediatric acute lymphoblastic leukemia (ALL) patients following at least two other failed treatments. The U.S. Food and Drug Administration recently declined approval for the use of Clolar in adult AML patients, citing the need for further clinical testing.

According to the authors, the most promising theme in recent Clolar studies is the efficacy of Clolar in treating elderly AML patients ages 60 years and above who are considered unlikely to benefit from standard chemotherapy.

It was also concluded that Clolar may be effective in the treatment of refractory and relapsed MDS, and its success in high-risk MDS patients has already been demonstrated. However, further studies are needed to establish the role of Clolar in MDS treatment.

The main MDS research detailed in the article was a Phase 2 study on the effects of Clolar as a single treatment agent in patients with high-risk MDS or one of several types of leukemia. In the MDS group, an overall response rate of 50 percent was observed, with 25 percent of patients achieving a complete response and 25 percent achieving a complete response with incomplete platelet recovery. Reversible liver toxicity was the most prominent side effect.

Combination treatments of Clolar with cytarabine (Cytosar-U) and idarubicin (Idamycin) in MDS patients were also examined.

In a Phase 1/2 study of Clolar given in combination with cytarabine to high-risk MDS patients as well as AML and ALL patients, an overall response rate of 38 percent was observed, with 22 percent achieving a complete response and 16 percent achieving a complete response with incomplete platelet recovery. Although both MDS and AML patients responded to the combination treatment, the exact response rate for the MDS group alone was not specified.

In a Phase 1 study, a combination of Clolar with both idarubicin and cytarabine was compared to a combination of Clolar with idarubicin alone in high-grade MDS and relapsed AML patients. A higher overall response rate was seen for the combination of Clolar with both idarubicin and cytarabine, with an overall response rate of 48 percent and 23 percent achieving a complete response. For the combination of Clolar with idarubicin alone, an overall response rate of 22 percent was observed.

One study compared the efficacy of oral Clolar with intravenous administration. The overall response rate was similar for both formulations, with an overall response rate of 37 percent for oral administration and 44 percent for intravenous administration.

In general, Clolar was tolerated well by patients in the studies. The most common side effects of Clolar and Clolar combination treatments were impaired liver function, swelling of hands and feet, and fevers and infections related to myelosuppression.

For more information, please see the study in the journal Expert Opinion on Investigational Drugs (abstract).