In late January 2010 the Journal of the National Cancer Institute (JNCI) came out with a highly positive article on hyperthermia or heat therapy (Twombley 2010). The stimulus for the article was a positive clinical trial with local hyperthermia in sarcoma reported at the European Society of Medical Oncology meeting in Berlin last fall. This randomized trial showed that patients given chemotherapy plus hyperthermia had a median disease-free survival of 32 months, whereas those who got chemotherapy alone had a survival of 18 months. Although this difference was statistically significant, there was no significant difference in overall survival. The most frequent side effect of hyperthermia (104 to 109º F) was "mild to moderate discomfort" (in 45 percent) whereas the most serious side effect was a severe burn seen in one patient (0.6 percent).

The lead investigator of that trial, Rolf Issels, MD, PhD, said that the treatment provided a "new standard treatment option." However, Issels continued, "the implications of these findings are more far-reaching. This is also the first clear evidence that targeted heat therapy adds to chemotherapy."

In the US, as well, long-time investigators of hyperthermia hailed the findings. "We are on a verge, I think, of a major new adjuvant cancer therapy that will not replace chemotherapy or radiation but will make them work a lot better," said Elizabeth A. Repasky, Ph.D., of Roswell Park Cancer Institute, Buffalo, N.Y., and president of the Society for Thermal Medicine, which promotes research and clinical use of hyperthermia.

Others expressed skepticism about the actual impact of the sarcoma trial. "I have been in the field 20 years, and I see how much benefit patients have, but institutions are not willing to use it," said Zeljko Vujaskovic, M.D., Ph.D., a radiation oncologist at Duke University Medical Center. Duke, a leading center of hyperthermia research, is the only US institution that participated in the Issels study.

The JNCI author, Renee Twombley, tries to provide some explanations for the neglect of hyperthermia, particularly in the US. These are basically (1) the technical demands of operating the hyperthermia equipment; (2) the current FDA requirement that probes be inserted into tumors in order to accurately measure temperatures; and (3) and "the historically low insurance reimbursement rates."

The lack of what Twombley calls "abundant evidence" that the treatment can affect overall survival also plays a role. This explanation avoids the question of why other cancer treatments, such as the drug Avastin (bevacizumab) for breast cancer, have also not been shown to affect overall survival, yet are approved by the FDA and by the oncology community as a whole.

"The dilemma we face," said researcher Peter Corry, PhD, "relates to premature clinical trials run in the early eighties that showed no benefit."

Another problem is that there is presently only one manufacturer of hyperthermia equipment in the US, BSD Medical Corp. of Salt Lake City. Advocates point out that there is a greater choice of innovative machinery available in Europe, as well as new thermal nanotechnology that may lead to breakthroughs in the field. (BSD's stock soared 37 percent, albeit temporarily, upon publication of the JNCI article.)

The article detailed the "checkered history" of hyperthermia with radiation or chemotherapy. In the 1970s and 1980s preliminary reports of benefit supported the use of mild termperatures to increase the effectiveness of radiation. Various devices using microwave, ultrasound or radio frequencies were built to treat tumors. These received pre-market approval from the FDA and in 1984 hyperthermia was approved for insurance reimbursement.

TO BE COMPLETED, WITH REFERENCES, NEXT WEEK

--Ralph W. Moss, Ph.D.

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