Studies involving the thermal (heating) mode for the treatment of pancreatic cancer 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 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 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 intervals 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.
Dale O’Brien, MD
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. 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 promising agent in the area of neuroendocrine tumors.
Dale O’Brien, MD
Again, for more than a decade there have been theoretical discussions about the use of drugs commonly used to treat high blood pressure for use in the treatment of cancer – pancreatic cancer.
And having just published a Pancreatica blog entry based on the pre-clinical study and work by Jain and colleagues from Harvard on the use of the angiotensin receptor blocker (ARB) high blood pressure medication losartan in the treatment of pancreatic cancer, we now present a kind of refutation of this premise in the form of actual Phase II clinical trial results using a different ARB, candesartan. By way of refresher, angiotensin receptor blockers relax muscle cells and cause blood vessels to dilate – possibly potentiating the effects of chemotherapy agents.
In the October 1st 2013 issue of the journal Investigational New Drugs, Koike and Japanese colleagues from the University of Tokyo have published the results of a Phase II multi-center clinical trial called GEGA2. These researchers enrolled 35 patients with confirmed advanced adenocarcinoma of the pancreas who had not received any prior chemotherapy. The patients were treated with a combination of gemcitabine and the ARB candesartan (up to 16 milligrams given orally).
The median progression-free survival was found to be 4.3 months; the overall median survival was 9.1 months. The one-year overall median survival rate of these patients was 34.2 %. The median progression-free survival was found to be significantly increased in those who received 16 mg of candesartan versus those who received just 8 mg. Modest or more low blood pressure was seen in three patients, and the candesartan was stopped in two of these. The primary side-effects were found to be hematological.
The authors conclude that the addition of candesartan did not significantly benefit patients over what would likely have been seen with the gemcitabine alone.
Does this doom the ARB hypothesis? No, this result was somewhat anticipated by the Harvard study. There, the researchers found that the significant effect that losartan had on the pancreatic adenocarcinoma stromal tissue in the vicinity of the tumor itself – appeared to be somewhat extreme and unique in the ARB family, including in the specific cited case of candesartan.
So the issue still remains: not as much about candesartan (given the results of this study by Koike et al.), but about the ARB losartan. Losartan as a potentiator of the effects of chemotherapy in the treatment of pancreatic cancer awaits further research.
Dale O’Brien, MD