A phase II study that investigated for the first time the effect of adding cetuximab to gemcitabine and oxaliplatin (GEMOX) for patients with advanced biliary tract cancer found that the disease responded in 63% of patients. Over a third of patients could then undergo an operation to remove the remaining tumour. These findings published Online First in The Lancet Oncology, indicate a promising first-line palliative care treatment for biliary tract cancers, and are the first to suggest a therapy that increases the chances of a surgical cure.

Although relatively uncommon, the incidence of biliary tract cancers is increasing worldwide. The only cure for these cancers reported so far is surgery to remove the tumour (resection), although the tumour often recurs afterwards. As symptoms are non-specific, most patients are diagnosed when resection is not possible. This means prognosis is poor and only 15% of patients remain alive for 5 years, including those who have resection.

No standard chemotherapy exists for this cancer, but adding cetuximab, an antibody against the epidermal growth factor receptor (EGFR), to GEMOX has improved the chances of a curative surgery in colorectal cancer.

In this prospective single-centre phase 2 study, Dr Birgit Gruenberger, (Barmherzige Brueder Hospital, Vienna, Austria) and colleagues aimed to investigate the therapeutic efficacy and safety of cetuximab plus GEMOX for palliative first-line treatment of patients with biliary tract cancers. Patients were included if they had advanced or metastatic biliary tract cancer, and if surgery was not possible (unresectable) due to the spread of the tumour to the liver or other organs.

Of the 30 patients enrolled in the study, 19 (63%) had a response (a tumour shrinkage of at least 30%) to the chemotherapy – 3 (10%) had a complete response and 16 (53%) had a partial response. In some other patients, treatment had a stabilising effect on tumour growth so the overall disease control rate was 80%. The tumour shrinkage was sufficiently large in 9 patients that a surgical operation could be done after chemotherapy to remove the remaining tumour tissue (secondary surgery).

The nine patients who had secondary surgery survived without progression of their disease for three times longer than those who did not have surgery (median 21.2 months compared with 6.8 months). More than 80% of the patients who had secondary surgery were still alive after 30 months of follow-up. Overall survival was 11·6 months in those ineligible for secondary surgery.

The chemotherapy combination was quite well tolerated, though treatment doses were lowered in 13 patients due to side effects. Cetuximab caused a rash in most patients, and the researchers found that response to treatment was best in those with the most severe rash. Other common adverse effects were nausea, anaemia, and peripheral neuropathy (nerve damage in the hands or feet).

The authors conclude: "In our study of patients with unresectable biliary tract cancer, we recorded a high overall response rate and good disease control after treatment with cetuximab and GEMOX. This combination treatment had an acceptable toxicity profile and resulted in potentially curative secondary resection in a third of patients, which significantly lengthened progression-free survival." These findings, they say, justify large, randomised studies of this chemotherapy combination.

Source: The Lancet