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Chemotherapy Regimen for NET: Platinum Agent Plus Topoisomerase Inhibitor

The exploration of chemotherapy for advanced pancreatic neuroendocrine tumors has been somewhat sparse, but has increased pace during the past few years. Certain of these regimens have met with some success, increasing the armamentarium of clinicians.

Beijing, China researchers led by Shen from the Peking University School of Oncology have published an article in the September issue of the journal Medical Oncology that examines the outcome of such a chemo regimen: the platinum drug cisplatin in combination with the topoisomerase I inhibitor, irinotecan (in the U.S. trade name Camptosar) in those with metastatic pancreatic cancer.

In years 2007 through 2009, sixteen patients with advanced and locally-advanced gastroenteropancreatic neuroendocrine tumors were treated with the cisplatin plus irinotecan combination therapy. Several of these patients were then transitioned to long-acting release octreotide after disease control had been reached.  The median duration of progression-free survival was found to be 5.5 months.  And the median overall survival of the patients was 10.6 months.  The primary serious side-effect of this treatment regimen was hematological. The authors conclude that this combination was reasonably well tolerated, and moderately effective.

This study is encouraging, and needs further confirmation.  But it does improve our understanding as to potential treatment options for those with more advanced neuroendocrine tumors.

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Dale O’Brien, MD

Heavy-duty Multimodal Therapy with RFA for Locally Advanced Pancreatic Cancer

In some ways, both early stage and late stage pancreatic cancer (under current thinking paradigms) may be easier stages in which to offer standard care: early receives surgery (without or without neoadjuvant or adjuvant augmentation), and late stage is typically chemotherapy in one combination or another – at least initially involving either gemcitabine or 5-FU.  These approaches are of course always changing as challenges move the cutting edge of science and medicine forward.  The recent modest breakthrough on nab-paclitaxel (Abraxane) plus gemcitabine presented by Von Hoff et al. in San Francisco in January is perhaps a case in point.

But at least for now, it is often the middle presenting disease stages – locally advanced pancreatic cancer – that do not present easier logical choices. So it is with some interest that we find in the August issue of HPB, the official journal of the International Hepato Pancreato Biliary Association, that Pederzoli and colleagues from Casa di Cura Pederzoli, Peschiera del Garda of Italy have published an intriguing study reflecting the results of an aggressive treatment protocol for locally advanced adenocarcinoma of the pancreas.

The researchers did a retrospective study of the outcomes of multimodal treatment (“Triple Treatment”) on locally advanced pancreatic cancer with radiofrequency ablation (“RFA”), radiochemotherapy, together with systemic as well as intra-arterial chemotherapy. They reviewed the results of 168 consecutive patients who had been treated with initial OR subsequent RFA (from 2007 until 2011), discovering that the median survival of these groups was roughly the same at about 25 months.  This was in comparison to the group which had received the more specific and aggressive Triple Treatment modality regimen which carried a subsequent overall median survival duration of 34 months.

This research carries the inherent limitations of what appears to be a nested retrospective study, but represents an interesting hypothesis – maybe especially in this time of more aggressive combinations (such as FOLFIRINOX)  – and as such is highly deserving of further study.

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Dale O’Brien, MD

Hepatitis as a Risk Factor for Cancer of the Pancreas

A number of “odd’ or non-intuitive relationships between “apparently” unrelated variables and pancreatic cancer are beginning to emerge – including ABO blood status and now some forms of hepatitis.

In the World Journal of Gastroenterology from July 14, 2013, Chen and colleagues from the Southern Medical University, in Guangzhou, China report a meta-analysis of a world review of the medical literature on the relationship between infection with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) AND pancreatic cancer. Using their developed criteria, they found eight studies that were eligible for inclusion in their analysis pool.

The researchers found a small but statistically significant association between chronic HBV and HCV infections and the risk of developing adenocarcinoma of the pancreas. The odds ratio for a patient’s status of the presence of inactive hepatitis surface antigen (HBsAg) and for chronic hepatitis B exposure was 1.2 at a 95% confidence interval – with Chinese patients appearing even somewhat higher (1.3). And the odds ratio for past exposure to the hepatitis C virus was somewhat similar at 1.26. The authors indicate that there is no evidence of publication bias in these associations.

It is not entirely clear what these findings mean. But finding association between pancreatic cancer and possible acute (or chronic?) triggers moves the science further along the cutting edge of understanding.

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Dale O’Brien, MD

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