Anticancer agent - sagopilone
Epothilone B is one of a number of related compounds originally extracted from the myxobacterium Sorangium cellulosum.
Epothilone B is one of a number of related compounds originally extracted from the myxobacterium Sorangium cellulosum.
As a microtubule stabilising agent, its mechanism of action is similar to that of the taxanes, but its structure is simpler and it is more water-soluble so the solubilising agents needed when administering paclitaxel are unnecessary. In addition, they are not recognised by efflux pumps, including the multidrug resistance protein, which may mean they could be useful in refractory tumours.
One epothilone analogue, ixabepilone, is already on the market from Bristol-Myers Squibb under the name Ixempra, and several others are being developed as potential anticancer agents. These include Bayer Schering's sagopilone, the first fully synthetic epothilone analogue.1
The drug is being investigated in a number of different solid tumours, including metastatic breast, lung, ovarian and prostate cancer, and glioblastomas because of its ability to cross the blood brain barrier. In one Phase II trial, patients who had had one or two relapses, and most of whom had previously been treated with taxanes, were given sagopilone in doses of 16 mg/m2 by infusion over either 30 minutes or three hours.2 The faster dosing schedule was quickly discontinued because of a low response rate. Four of the 13 evaluable patients on the three-hour schedule had a response, and the major side-effect reported was neuropathy.
It is also being investigated in non-small cell lung cancer. A total of 44 patients with stage 3 or 4 NSCLC who had relapsed after platinum chemotherapy were given 16mg/m2 doses of the drug over a three-hour period every three weeks for up to six cycles.3 Four of the first 38 patients to be evaluated responded, which is comparable to other second line therapies. Seven of the subjects discontinued because of neuropathy, with other reported adverse events including myalgia, nausea, vomiting, hair loss and fatigue. The trial is continuing, with new patients enrolled in the trial being given doses of 22mg/m2.
Various other clinical studies are also underway in different tumour types.