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Zolinza, Idarubicin, Cytarabine Combination Yields High Response Rates In MDS Patients (ASH 2011)

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Published: Jan 11, 2012 2:36 pm
Zolinza, Idarubicin, Cytarabine Combination Yields High Response Rates In MDS Patients (ASH 2011)

Sequential treatment with Zolinza, idarubicin, and cytarabine is safe and highly effective in patients with acute myeloid leukemia and higher-risk myelodysplastic syndromes, according to results from a recent Phase 2 study.

The study authors also found that patients with mutations in the FLT-3 gene responded particularly well to the drug combination, yielding an overall response rate of 100 percent.

Dr. Guillermo Garcia-Manero of the MD Anderson Cancer Center in Houston presented these findings at the 2011 American Society of Hematology (ASH) conference in San Diego last month.

Zolinza (vorinostat), which is marketed by the U.S. pharmaceutical company Merck, is an oral drug already approved in the United States for a certain type of lymphoma. It also is approved for a similar use in Canada and Australia, but not in Europe.

Zolinza belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which work by increasing the production of proteins that slow cell division, repair DNA mistakes, and control cell death. The drug panobinostat, which has been investigated as a potential treatment for myelodysplastic syndromes (MDS), belongs to the same class of drugs.

Zolinza is currently being investigated in combination with various other drugs as a potential treatment for MDS and another blood cancer called multiple myeloma. Recent results have shown that MDS patients in poor health may benefit from treatment with Zolinza in combination with Vidaza (azacitine) (see related Beacon news).

In preclinical studies, Zolinza showed anti-leukemia activity when combined with idarubicin (Idamycin) or cytarabine (Cytosar-U).

In the present study, the researchers evaluated the safety and activity of Zolinza, followed by idarubicin and cytarabine, as first-line treatment in 75 patients with acute myeloid leukemia and higher-risk MDS.

The median patient age was 52 years. In addition, 39 percent of patients had a normal number of chromosomes; 15 percent had mutations in the gene coding for the protein FLT-3. Mutations in the FLT-3 gene can lead to cancer.

Patients received 500 mg of oral Zolinza three times daily (on days 1 to 3 of the treatment cycle), 12 mg/m2 of intravenous idarubicin three times daily (on days 4 to 6 of the treatment cycle), and 1.5 gm/m2 of intravenous cytarabine continuously (on days 4 to 7 of the treatment cycle).

The overall response rate was 85 percent, with 76 percent achieving complete remission. For patients with FLT-3 gene mutations, the overall response rate was 100 percent.

At a median follow-up of 82 weeks, the median overall survival and event-free survival times for the overall patient population were 82 weeks and 47 weeks, respectively. Patients with FLT-3 gene mutations had better overall survival (91 weeks) and event-free survival (66 weeks) than the overall patient population. Patients with normal chromosomal numbers also had higher overall survival and event-free survival times (105 weeks and 68 weeks, respectively).

The most common side effects were diarrhea (73 percent), nausea and vomiting (65 percent), and skin reactions (38 percent). Four percent of patients died from treatment.

For more information, please see abstract 763 at the ASH 2011 meeting website.

Photo by IndyDina with Mr. Wonderful on Flickr - some rights reserved.
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