Researchers at Dana-Farber Cancer Institute in the USA reported the results of the single-agent trial of the drug, called MLN8237, developed as a treatment for ovarian cancer.

MLN8237 selectively inhibits an enzyme known as Aurora A kinase, which is a member of a family of kinase enzymes involved in normal cell division. Researchers have found that Aurora A kinase is over-expressed in some cancer cells, leading to growth of cancers.

In addition to ovarian cancer, the Aurora A kinase gene is amplified or overexpressed, or both, in other cancers including colon, breast, pancreatic, and bladder cancers, as well as certain lymphomas, leukemias and myeloma.

Unlike other Aurora kinase inhibitors currently being studied, MLN8237 selectively targets Aurora A Kinase and can be administered orally.

In the current study, researchers treated 31 patients whose cancer was resistant or refractory to Platinum-based chemotherapy and who had tried at least three other therapies. Twenty-five patients had ovarian cancer, 5 had primary peritoneal cancer, and one had Fallopian tube carcinoma.

The patients received MLN8237 in 21-day cycles: seven days of twice-daily 50mg treatment, followed by a 14-day break. Three patients had a partial response to the treatment, and 5 had stable disease that was sustained for at least four 21-week cycles.

The most important finding from this study was the fact that MLN8237 has demonstrated single-agent activity in ovarian cancer with encouraging durable disease control in some patients. Several patients have remained on the study drug for over 12 months.
The fact that multiple patients had stable disease or response suggests that future development of MLN8237 in combination with other active agents may be a promising avenue to investigate.

The researchers noted that the MLN8237 had various toxicities. The most common serious toxicities included neutropenia, stomatitis, leucopenia, thrombocytopenia and fatigue, which were generally reversible during the 14-day break in treatment. Five patients discontinued due to adverse events.

Source: ESMO Meeting, 2010

XagenaMedicine2010


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