Anticancer agent - phenoxodiol
Numerous different signal transduction chemicals are responsible for the healthy life and death of cells. Cancer results when these cells begin to respond incorrectly to these signals, and instead of undergoing apoptosis or programmed cell death, they survive and proliferate when they should not.
Numerous different signal transduction chemicals are responsible for the healthy life and death of cells. Cancer results when these cells begin to respond incorrectly to these signals, and instead of undergoing apoptosis or programmed cell death, they survive and proliferate when they should not.
A way of preventing this would be to inhibit the pathways that lead to cell survival and restore a normal balance of the signalling processes; multiple signal transduction regulating drugs are designed to do this.
One potential drug in this class is phenoxodiol, also referred to as idronoxil, which was discovered by Australian company Novagen and is being commercialised by its subsidiary, Marshall Edwards.1 It is an analogue of the plant isoflavone genistein, which itself has some anticancer activity, but phenoxodiol was designed to improve its activity and absorption. It has several anticancer effects, including antiangiogenesis, modulating proteins involved in the apoptosis pathways, and cell cycle arrest.
Several trials have been carried out in cancer patients. In one Phase Ib study, it was investigated as monotherapy in patients with advanced ovarian cancer who had failed at least two previous chemotherapy regimes. They were given 1, 3, 10 or 20mg/kg intravenously. About 10% achieved stable disease at three months, and one remained progression free for 36 weeks. A quarter of the 40 patients had a response after six weeks. It was also found to have a resensitising effect in some patients who were subsequently given paclitaxel.
In a Phase II study, women with recurrent ovarian, fallopian or primary peritoneal cancer that were refractory or resistant to taxanes or platinum drugs were given 3mg/kg of phenoxodiol on two consecutive days per week along with weekly doses of paclitaxel or cisplatin on the second of these days, in six-weekly cycles.2 Treatment normally continued for eight cycles. A total of 71% of those on the cisplatin regime achieved a complete response, partial response or stable disease, and 74% of those taking paclitaxel. The median overall survival overall survival was 62 weeks for the cisplatin group, and 48 for paclitaxel, compared to 28-40 weeks for those given just the standard therapy. Phase III studies are now under way.