Dr. Fowell agrees that CUP tumors behave differently from known primary tumors and said that many CUP patients present late when their performance score is already quite poor. “We saw that as a really important factor that people need to make an early decision as to whether we should be pursuing invasive investigations when at the end of the day they may not be fit for treatment anyway,” he said, noting that data suggests that as few as 8% of CUP patients go to chemotherapy.
The NICE guidelines recommend that investigations be performed only if they affect a treatment decision; and the patient understands why the investigation is being done, the potential benefits and risks of the investigation and treatment, and is prepared to accept treatment.
The NCCN guidelines recommend that chemotherapy for patients with disseminated disease should be limited to symptomatic patients with a performance score of 1-2 or asymptomatic patients with aggressive disease.
Dr. Nicholas Pavlidis
NICE, which calls CUP a “neglected disease” contends that patients with CUP are largely denied the medical and other benefits afforded those with site-specific cancers because of a lack of specific, dedicated clinical services, a lack of understanding and information about the disease, and the absence of a formal research structure. The guidelines call on every hospital with a cancer center or unit to establish a CUP team, comprising an oncologist, palliative care physician, and a CUP specialist nurse or key worker as a minimum, said Dr. Fowell, a consultant in palliative medicine at Bangor Hospital in North Wales.
NICE also suggests that a clinical studies group be established for CUP at the National Cancer Research Network level to coordinate and direct clinical trials. There has been a paucity of research, but new studies are in the works. The open-label, phase II UNKPRI 21 trial, also based in Nashville, compares carboplatin/paclitaxel with carboplatin/paclitaxel plus the histone deacetylase inhibitor PXD101 (belinostat) in patients with previously untreated CUP. The United Kingdom’s CUP-ONE trial is prospectively validating three molecular classification techniques and assessing the feasibility of combining the established chemotherapy regimen epirubicin (Ellence), cisplatin and capecitabine (Xeloda) with erlotinib.
Dr. Fowell and Dr. Pavlidis disclosed no conflicts of interest. Dr. Ettinger disclosed relationships with 11 companies including Genentech, which markets bevacizumab and erlotinib.