Thursday, 21 March 2013

Dasatinib is safe but not effective against myelodysplastic syndrome

Researchers at Moffitt Cancer Center just announced the results of a phase II clinical trial on patients with with higher-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia, or acute myeloid leukaemia arising from MDS, who had previously failed to respond to conventional treatment (azanucleosides). Purpose of the trial was to assess the safety and efficacy of dasatinib in treating these conditions. The researchers say that although the drug won't help all patients, it does help the ones with the trisomy 8 chromosomal disorder.

Myelodysplastic syndrome (formerly known as preleukemia) is a diverse collection of haematological medical conditions involving the ineffective production of the myeloid class of blood cells. Essentially, it is a disorder of the bone marrow stem cells, leading to an inability to produce adequate amounts of blood cells. As time passes, the amount of blood-forming stem cells reduces and blood production is impaired accordingly.


Image of an enlarged spleen due to myelodysplastic syndrome
Enlarged spleen due to myelodysplastic syndrome (Spleen in red, left kidney in green)

The only curative option is receiving a stem cell transplant, however the outlook is really poor with survival rates of only 50% at 3 years, with older patients doing even worse. According to the researchers the only FDA-approved drug is a class of medication called azanucleosides, and again the prognosis tends to be very poor.

Purpose of this study was to examine if a drug called Dasatinib is efficient against the aforementioned conditions. The drug has already received approval from the FDA for chronic myelogenous leukemia and the researchers say it is promising due to its activity against a broad spectrum of tyrosine kinases, including those in the Src family. It is believed that Src pathways contribute significantly in the tumorigenetic process.

“Given the evidence for the role of Src kinases in myeoblast proliferation and the laboratory tested inhibitory activity of dasatinib on Src, especially on the Lyn kinase, we conducted a phase II study to assess the overall response to 100 mg per day dasatinib in patients with higher risk MDS who had failed previous treatments,” said Rami S. Komrokji, corresponding author.


During the trial, a total of 18 patients participated, all given100mg of dasatinib in a daily basis. Toxicity reports were limited and consistent with previous reports, indicating that Dasatinib is safe to use.

Regarding the drug's efficacy:
  • 3 patients responded
  • 4 had stable disease,
  • 10 experienced disease progression
Reportedly, five of the patients had trisomy 8, a chromosomal disorder characterised by having three copies of chromosome 8. The condition stabilised in the four of them after receiving treatment.

The study concludes that although safe, Dasatinib has limited efficacy.


An overview of myelodysplastic syndrome

Reference
Duong, V., Jaglal, M., Zhang, L., Kale, V., Lancet, J., Komrokji, R., & List, A. (2013). Phase II pilot study of oral dasatinib in patients with higher-risk myelodysplastic syndrome (MDS) who failed conventional therapy Leukemia Research, 37 (3), 300-304 DOI: 10.1016/j.leukres.2012.11.001

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