Monday, 22 July 2013
An important target in cancer treatment is the serine/threonine specific protein kinase Akt, or protein kinase B. This kinase is involved in the pathway that prevents cell death, inhibiting apoptosis, and therefore inhibiting Akt may lead to cancer cell death.
One such compound is perifosine, discovered by Aeterna Zentaris and being developed by Keryx Biopharmaceuticals.1 Numerous clinical trials have been carried out in solid tumours, with varying success, and it failed a Phase III trial in colorectal cancer in 2012. However, it continues in trials for blood cancers such as lymphomas, where it shows promise.
In one Phase I/II trial, it was evaluated in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma who had previously received bortezomib therapy.2 A total of 84 patients, three-quarters of whom were refractory to bortezomib, and half to both bortezomib and dexamethasone, were given 50mg/day of perifosine, plus 1.3mg/m2 bortezomib, and 20mg dexamethasone added if progression occurred. The overall response rate was 43% in the 73 evaluable patients – 65% in the bortezomib-relapsed group and 32% in bortezomib-refractory patients. It was generally well tolerated, with manageable gastrointestinal events and fatigue. The median progression-free survival was 6.4 months, and a median overall survival of 25 months – 22.5 months in those refractory to bortezomib.