Depending on who you are and how you count, there are almost twenty kinds of pancreatic cancer. The main two that we generally speak of are adenocarcinoma of the pancreas which arises from the non-hormonal part of the organ and may be responsible for as much as 85% of cases, and pancreatic neuroendocrine tumors (NETS) from the hormonal part of the pancreas – which true incidence is not fully established, but we might say represent about 10% of pancreatic cancer diagnosis.
There are many differences between these two main types of malignancy: natural history, signs and symptoms, treatment, and prognosis. From a functional practical sense, there is also one big difference that we have seen: often adenocarcinoma has presented itself with a diagnosis fairly easily – so that treatment is often the issue. And neuroendocrine tumors are often elusive in diagnosis – sometimes for years – so here diagnosis is often a primary issue.
So, it is with interest that we encounter research by Frocione and his Illinois colleagues presented in the June 21st issue of the World Journal of Gastroenterology that reviews medical literature in terms of the use of the accuracy of the technique of endoscopic ultrasound (EUS) in the diagnosis of pancreatic neuroendocrine tumors.
The researchers reviewed over 2,600 articles in the medical literature, selecting 140 for further scrutiny, and eventually settled on thirteen that met their inclusion criteria. They extracted and pooled data from these studies to ascertain sensitivity, specificity and other parameters for the use of endoscopic ultrasound for pancreatic neuroendocrine diagnosis. They found that the pooled sensitivity of EUS in detecting pancreatic NETs was 87.2 percent; the pooled specificity was 98.0 percent.
The researchers conclude that endoscopic ultrasound appears to be a good way to establish the diagnosis for neuroendocrine tumors. There are limitations to this kind of study, but it is highly interesting and relevant – and certainly worthy of further follow-up and confirmation.
Dale O’Brien, MD
Recent advances over the drug agent gemcitabine for advanced pancreatic cancer are still in progress but appear to include the FOLFIRINOX (5-FU based) combination regimen and now recently Abraxane plus gemcitabine.
Now comes a study by German researchers Lorenz and colleagues from the University of Frankfurt as published in the August issue of the journal Hepatogastroenterology which looks at the regimen that uses intravenous and intra-arterial gemcitabine and the oncology agent Mitomycin C in the treatment of advanced pancreatic cancer.
This was a Phase II study with 17 patients with diagnosed advanced cancer of the pancreas who were given the regimen and followed. The median progression free duration was 4.6 months; and the median overall survival duration was 9.1 months for the patients. The most frequent side-effects were hematologic. The authors suggest that this regimen may give improved survival results over gemcitabine given alone, and perhaps comparable results as that of the FOLFIRINOX regimen, but with fewer side-effects.
This is research that requires further study and follow-up !
Dale O’Brien, MD
On September 6th the U.S Food and Drug Administration (FDA) – per its commendable fast track expedited review program for “orphan” diseases (which now includes pancreatic cancer) has approved nab-paclitaxel (trade name: Abraxane) for use in in combination with gemcitabine for metastatic pancreatic cancer. The previous drug agent officially approved by the FDA for pancreatic cancer (occurred on November 2, 2005) was the targeted agent erlotinib (trade name: Tarceva) in combination with gemcitabine.
This rather remarkable rapid FDA approval stems from the outcomes of the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPAC study) presented this past January in San Francisco at the American Society of Clinical Oncology’s 2013 Gastrointestinal Cancers Symposium by Daniel Von Hoff, MD, the physician-in-chief and director of Translational Research at the Translational Genomics Research Institute.
Paclitaxel is one of the taxane family of drug agents, and available in the U.S. as Taxol, which is approved for use in the treatment of several cancers. Nab-paclitaxel has been developed by the Calgene biotech company and is formed by adding the protein molecule albumin to the drug complex. Abraxane has previously been approved by the FDA for use in metastatic breast cancer and non-small cell lung cancer.
One interesting fact is that Dr. Von Hoff also led the research team that developed the work resulting in the 1996 FDA approval of gemcitabine for the treatment of pancreatic cancer.
MPAC was a multi-country, multi-center (151 community and academic centers) Phase III clinical trial involving 861 patients with previously untreated advanced pancreatic cancer who were randomly assigned to one of two arms: to receive either standard gemcitabine treatment OR to receive 125/m2 of nab-paclitaxel followed by standard gemcitabine treatment.
The MPAC patient group that was given the Abraxane/gemcitabine combined therapy demonstrated a 59% increase in the 12-month median survival rate above the group that had been treated with only gemcitabine. The Abraxane combination arm showed about a two month increase in overall survival advantage above the gemcitabine single treatment arm (8.5 months versus 6.7 months). Also, the 12-month survival rose from 22% to 35% in the group that was given the combination regimen at an impressive P=0.0002. The 2-year survival was still poor but increased with the combination to 9% from 4% over single therapy.
It would seem that the FOLFIRINOX regimen presented in 2011 and now this Abraxane/gemcitabine regimen appear to represent modest but definite advantage in the treatment of metastatic adenocarcinoma of the pancreas. Further research will undoubtedly further illuminate the nature and extent of these particular advantages – and present indications for these and single therapy (gemcitabine) as first-line treatment standard of care.
Dale O’Brien, MD