The drug was given in pill form once a day, and the researchers found that the maximum tolerated dose was 300 mg a day. Dr Robert Wenham, Clinical Director for Gynecologic Oncology in the Department of Women's Oncology at the Moffitt Cancer Center, who is presenting data on behalf of the participating investigators, said: "MK-4827 is generally well tolerated, with the main dose-limiting toxicity being thrombocytopenia an abnormal decrease in the number of platelets in the circulatory blood. The most common side effects are mild nausea, vomiting, anorexia and fatigue."
The researchers saw anti-tumour responses in both sporadic and BRCA1/2 mutation-associated cancers. Ten patients with breast and ovarian cancers had partial responses, with progression-free survival between 51-445 days, and seven of these patients are still responding to treatment. Four patients (two with ovarian cancer and two with NSCLC) had stable disease for between 130-353 days.
Dr Wenham said: "Most patients in the trial had exhausted standard therapies and those who responded to this drug have benefited. Several patients have been receiving treatment for more than a year. The responses mean that MK-4827 is working as hoped and justify additional studies. Just how well MK-4827 works compared to other treatments is the goal of the next set of studies."
He gave a possible explanation as to why patients with cancers that were not caused by BRCA1/2 mutations also responded to the PARP inhibition. "BRCA is a tumour suppressor gene that assists in repairing double stranded DNA breaks. In BRCA-mutation related cancers, loss of both copies of the gene results in a non-functional protein and thus BRCA deficiency. Because BRCA works with other proteins, BRCA-pathway related deficiency can be seen in the absence of two mutated copies of the BRCA g
|Contact: Emma Mason|
ECCO-the European CanCer Organisation