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FOLFIRINOX (Minus Irinotecan) for Gemcitabine-refractory Pancreatic Cancer

Since the promising article on the 4-drug 5-FU led FOLFIRINOX regimen for metastatic pancreatic cancer (ductal adenocarcinoma of the pancreas) per the May 12, 2011 article in the New England Journal of Medicine, this treatment approach has emerged as a solid first-line option.  In the ensuing months there have been a number of studies exploring further options with this 4-drug combination, including for other stages in cancer of the pancreas.

Now comes interesting research by Wahba and El-Hadaad of Mansoura University, Egypt as published in the September 2013 issue of the Journal of Gastrointestinal Cancer looking at a somewhat truncated version of this regimen in patients whose advanced pancreatic cancer showed progression after treatment with gemcitabine.

In a phase 2 clinical trial, the authors treated thirty such patients with a regimen that included 5-FU (fluorouacil), folinic acid, and oxaliplatin (the FOLFIRINOX regimen without irinotecan) with tolerable (adjudged) side-effects and a median overall survival of 22 weeks, and a six-month survival rate of 30%. They conclude that this regimen is active and in need of further study.

We concur. Very interesting work – that would benefit by follow-up research.

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Dale O’Brien, MD

Microwave “Surgery” for Pancreatic Cancer

Studies involving the thermal (heating) mode for the treatment of pancreatic cancer (ductal adenocarcinoma of the pancreas) have generally concentrated on radio waves. This form of “surgery” is called ablation – and of course is not surgery at all, but the destruction of tumor tissue by heating it to levels that cause cell death.  Generally, the range of 120 to 140 degrees (Fahrenheit) will cause coagulation and then cell death in a matter of minutes. Temperatures above this will cause immediate tissue death.

Radio waves and microwaves can each heat tissues to these levels, but their mechanisms are quite different. Radiofrequency ablation (RFA) relies on electrical current running through the tissue in the form of a complete circuit.  It works because ion rich fluid permeates the human body.  And as body tissue is not a perfect electrical conductor, a resistive rise in temperature occurs.

Microwave ablation is a form of dielectric heating based on an alternating electromagnetic field, and in which the tissue itself is the dielectric material. Water molecules in the tissue are forced to oscillate, with some bound molecules oscillating out of phase – causing energy to be converted to heat.

Thus microwave heating tends to occur in the space around the applicator wand, while radio frequency heating is limited to specific areas created by high electrical current. Radiofrequency ablation (RFA) has increasingly been shown to be an effective modality in the treatment of tumors in such organs as the liver, lung and kidney.  But due to its reliance on tissue properties, RFA can be somewhat limiting. Microwaves are less effected by tissue properties and offer very good penetration. However, there has not been a long history with commercial or academic microwave systems, and correspondingly there have been less studies involving microwave ablation for the treatment of cancer.

So it is with great interest that we read the recent research by Carrafiello and colleagues from the Division of Interventional Radiology, Department of Radiology at the University of Insubria in Varese, Italy as published in the October 2013 issue of the Journal of Vascular and Interventional Radiology which reports on microwave ablation for pancreatic cancer.

The researchers treated ten patients who had adenocarcinoma located in the head of the pancreas with a microwave generator for ten minutes at intermittent intervals for up to 12 months.  The tumor response was measured, and the safety and effectiveness of the procedure was evaluated.

The authors report that the procedure was feasible in all of the patients.  They indicate that there was one major complication which occurred but was resolved.  That the patients quality of life tended to improve after the microwave applications, but that this tended to revert to pre-procedure levels in weeks to months after the intervention. They conclude the microwave ablation appears to be encouraging and feasible in the palliative care of pancreatic cancer.

This is an interesting study of an under-studied intervention.  Microwave ablation in the treatment of pancreatic cancer deserves further inquiry.

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Dale O’Brien, MD

Clinical Trial Results with Votrient for Advanced Neuroendocrine Tumors

Votrient (pazopanib) is a drug-agent of GlaxoSmithKline that appears to work through targeting angiogenesis and growth pathways, and has been approved for use in renal cell carcinoma and advanced soft tissue sarcoma, and now is under study for use in neuroendocrine tumors. Two other recent targeted agents that have been approved by the U.S. FDA for the treatment of neuroendocrine tumors are everolimus and sunitinib.

Park and colleagues at Gachon University in Korea have recently published the results of a Phase II clinical trial using pazopanib as a single agent in the treatment of gastrointestinal and pancreatic neuroendocrine tumors in the British Journal of Cancer.

The authors treated 37 patients with metastatic neuroendocrine tumors with pazopanib in 2010 to 2012. The patients in the study showed an objective response rate of 18.9%. An independent review demonstrated a higher overall response rate of 24.3%, with nine confirmed partial responses.

The authors suggest that this effect appears to be similar to that of other recent targeted therapies, which provides impetus for further study of this potential agent for consideration in the area of neuroendocrine tumors.

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Dale O’Brien, MD

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