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Nanoliposomal Topoisomerase I Inhibitor for Advanced Pancreatic Cancer

There is no universally agreed upon second line treatment for metastatic pancreatic cancer (ductal adenocarcinoma of the pancreas). On August 20 2013 in the British Journal of Cancer, the results of an interesting international Phase II clinic trial using nanoliposomal irinotecan for the treatment of earlier pre-treated metastatic pancreatic cancer were published. The researchers included Dr. Margaret Tempero, who is on our Pancreatica Science Board.

The study included 40 patients with metastatic pancreatic cancer who were now considered refractory to earlier treatment with gemcitabine, and who were then given the drug agent PEP02, also known as MM-398 (or Irinotecan Sufosulcrate) as developed by the biotech companies PharmaEngine and Merrimack. This is a nanoliposome, which indicates that the drug molecule is contained in a spherical coating of a lipid or fatty-like substance.

The essential aim of this study was to ascertain the 3-month survival rate in these pancreatic cancer patients with this therapy. The researchers observed 3 patients who demonstrated an objective tumor response.  Over at least two treatment cycles 17 other patients showed evidence of stable disease. 10 patients (of 32) with elevated CA19-9 levels, showed a greater than fifty percent decrease in these levels. The median progression-free duration was 2.4 months. The overall 3-month survival rate was 75%.  And the median overall survival was 5.2 months.

The researchers note that the more common side-effects of this treatment were asthenia, abdominal discomfort, neutropenia and diarrhea.

The authors conclude that at this stage of study the apparent activity of liposomal irinotecan coupled with a relatively tolerable side-effect profile make it a promising candidate for second-line consideration.  Currently Phase III trials are underway.

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Dale O’Brien, MD


EUS for Neuroendocrine Tumors

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 ductal 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 late but often fairly easily – so that treatment is typically the issue. And neuroendocrine tumors are often elusive in diagnosis with perplexing signs and symptoms  – sometimes for years – so here diagnosis is often the primary issue.

So, it is with interest that we encounter research by Frocione and his Illinois colleagues presented in the June 21st 2013 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.

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Dale O’Brien, MD

IA and IV Gemcitabine plus Mitomycin-C for Pancreatic Cancer

Recent advances over the drug agent gemcitabine for advanced pancreatic cancer (ductal adenocarcinoma of the pancreas) are still in progress but the current strong regimins for first-line therapy 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 a regimen that uses intravenous and intra-arterial gemcitabine plus 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. 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 !

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Dale O’Brien, MD