Oral Fludarabine as Good as IV for Untreated CLL

December 09, 2002

Jane Salodof MacNeil

Dec. 9, 2002 (Philadelphia) A multicenter European study has found that a new oral formulation of fludarabine phosphate (Fludara) is comparable to the intravenous (IV) version for patients with previously untreated B-cell chronic lymphocytic leukemia (CLL).

Jean-Francois Ross, MD, head of hematology/oncology at University Hospital in Montpellier, France, presented results here at the American Society of Hematology annual meeting. The overall response rates were 71.6% according to criteria of the International Working Group on CLL (IWCLL) and 80.2% by National Cancer Institute (NCI) criteria.

"The oral formulation is more convenient, and it will be cheaper because you have no hospitalization," Dr. Ross told Medscape.

In the open-label study, 81 patients were given 40 mg/m 2 of fludarabine daily in 10-mg tablets for five days. The treatment was repeated every four weeks for up to eight cycles, with most patients achieving a response after six cycles.

For comparison, the investigators relied on published data for untreated patients who received fludarabine intravenously. Intravenous treatment was usually given on the same schedule, but in 25-mg/m 2 daily doses lasting 30 minutes.

The patients in the new study came from 24 cancer centers in Belgium, France, Italy, the Netherlands, and the U.K. Their average age was 64 years, and nearly two-thirds were male.

Under NCI criteria, 12.4% had complete remission, 67.9% had partial remission, and 11.1% had stable disease. Six patients had progression of their disease.

The disease stage of the patients when starting therapy seemed to influence the result. Overall response was 80% for patients who were Binet A progressive, but the response rate decreased to 75% for Binet B and 53% for Binet C.

Adverse effects were frequent. Nausea and vomiting were more common with the oral version, and 18 patients had serious adverse events. Dose reductions were necessary for 14 patients, three patients stopped treatment because of adverse events, and four patients died one of septicemia during treatment and three of myocardial infarction seven to 14 months after treatment.

Dr. Ross said most toxicities were brief, however, and standard for chemotherapy. The poster described the oral version as well tolerated and said the toxicities were not unexpected.

The oral version has been approved in 32 countries and is widely used as a second-line treatment outside the U.S., according to Marcus Klein, head of clinical development, oncology, in Europe for drug manufacturer Scherring AJ of Berlin. The company is hoping to win U.S. approval, he said.

So far, its application has not been successful because the U.S. Food and Drug Administration has not accepted the European data, Klein said. He described the problem as stemming from different methods of evaluation in Europe and the U.S.

Asked whether the company would undertake a trial in the United States, Klein said he could not say what its next step will be.

Kanti R. Rai, MD, chief of hematology/oncology at Long Island Jewish Medical Center in New Hyde Park, N.Y., is the author of a previous study comparing fludarabine to chlorambucil for CLL. He described the new data as positive and not surprising. "Oral absorption has been well established," he told Medscape, calling the European investigation "the first step to demonstrating the [oral] drug has clinical activity."

ASH 44th Annual Meeting: Abstract 1491. Presented Dec. 7, 2002.

Reviewed by Gary D. Vogin, MD

Jane Salodof MacNeil is a freelance writer for Medscape.


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