"Researchers have developed a novel immunoassay for detecting early-stage pancreatic cancer that identifies and quantifies blood levels of the PAM4 protein – a unique antigen present in almost 90 percent of pancreatic cancers and precancers."

ASCO GI Cancer Symposium, 2010

Wow, that little snippet from the ASCO press releases from the Gastrointestinal symposium in Florida woke me up while sipping coffee this morning!

The reason is that pancreatic cancer is an insidious disease and most patients are diagnosed late, usually in stage IV when there is little that can be done to successfully attentuate the cancer.  For years, researchers have struggled with ways of detecting the cancer earlier when treatments are more likely to be effective without confusing cancer from pancreatitis.

Approximately 7% of pancreatic cancer cases are detected at an
early stage, before the cancer has spread to other parts of the body. 
The survival rate for early stage pancreatic cancer is around 20%, compared with just 1.8% for those diagnosed when the disease has metastasized.

The PAM4 antibody, also called clivatuzumab, from Immunomedics ($IMMU) used in the assay reacts with a protein produced by pancreatic cancer cells.  It appears that the protein is not detectable in normal pancreatic cells and is rarely detected in pancreatitis (inflammation of the pancreas), making it potentially highly specific for pancreatic cancer.

The researchers evaluated an immunoassay for the PAM4 protein in 68 patients who had pancreatic cancer surgery and 19 healthy controls.  They found that the test was 62% sensitive for detecting stage 1 pancreatic cancer (disease confined to the pancreas), 86% sensitive for stage 2 disease (disease which has spread to nearby organs) and 91% sensitive for stage 3/4 cancers (local and distant spread).  Overall, the assay was 81% sensitive for detecting all stages of pancreatic cancer; while not perfect, it would represent an enormous improvement on current detection rates.

The obvious next step is to validate the test on a larger scale with more patients to determine if it has utility as a diagnostic tool to detect people at risk for pancreatic cancer such as patients with a history of tobacco use, or those with genetic or other medical factors on a yearly basis, to enhance the chance of early detection.

The investigators also suggested that the clivatuzumab antibody may also prove useful for treating the disease by acting as a carrier for agents (such as radioactive isotopes labelled with Y90) that can target and kill cancer cells, but this idea is pure supposition at present and as yet, unproven.  Immunonomedics have a phase I trial ongoing with clivatuzumab in pancreatic cancer

At the ASCO GI symposium there was, however, some interesting new data in the treatment of pancreatic cancer as Pfizer announced the final results from a randomized Phase III
trial of sunitinib (Sutent) in patients with advanced pancreatic
neuroendocrine tumors, a type of cancer which originates in the
hormone-producing area of the pancreas. 

Sunitinib appeared to more than double the
time the patients with lived without
disease progression compared with patients treated with placebo; results showed that median progression-free survival (PFS) was 11.4
months in patients treated with sunitinib compared with 5.5 months in
patients treated in the placebo arm.  Overall survival was also prolonged. 
Adverse events were similar to those observed in other sunitinib

The sunitinib results are particularly interesting, not only because they improve survival beyond the six months typically seen with the disease, but also because other VEGF inhibitors such as bevacizumab (Avastin) previously did not appear to be effective in slowing the disease.  Sunitinib, though, is a multi-kinase inhibitor that also targets other pathways other than VEGF, including c-KIT, PDGF, FLT3 and RET, suggesting that dual inhibition of perhaps VEGF and PDGF is necessary in this disease.

On the basis of these results, Pfizer filed supplemental applications
for approval in pancreatic neuroendocrine tumours with the US, EU and
Canadian authorities, so help for patients may well be coming sooner than expected.

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