[ot] A Big Boost For Hyperthermia - Part II

[Guest guest]

A Big Boost For Hyperthermia - Part II

Sunday, 14 February 2010

LAST WEEK WE BEGAN A TWO-PART NEWSLETTER ABOUT THE JNCI HYPERTHERMIA

ARTICLE. WE CONCLUDE THIS WEEK.

In 1984 hyperthermia was approved for insurance reimbursement. Then came

some major setbacks. Clinical trials conducted by the Radiation Therapy

Oncology Group (RTOG) failed to show clinical benefit. In one large

randomized, controlled study there was little difference in response between

patients who received radiation compared to patients who were treated with

hyperthermia and radiation for localized tumors. This was a body blow to

hyperthermia ( 1991; also Emami 1996).

Amazingly, however glaring issues of quality control could probably account

for the negative result, according to researcher Corry, PhD. For

instance, in the aforementioned trial, different centers used different

equipment, and 75 percent of the tumors treated were so large that heating

the entire mass to an average of 43º C, the standard at the time, was not

possible.

Also, says the JNCI, almost one-third of the tumors that were treated were

never tested for an internal temperature, so it was not certain that the

tumors in question were ever actually heated! Problems with equipment and

technique also emerged in the course of the trial. The machinery had

difficulty maintaining a uniform tumor temperature and, in any case,

researchers did not know what was an effective dose. Mark Dewhirst, DVD,

PhD, of Duke University has reviewed the study and said that the design was

clearly inadequate.

But the negative study had its effect. The general enthusiasm for

hyperthermia (once called oncology's fourth modality) soon dwindled, as did

the research funds and insurance reimbursement. Companies stopped making the

devices, which in any case were probably ineffective. In fact, many of

today's researchers blame the FDA for approving these devices for use in

general practice, which in their eyes severely tainted hyperthermia. Most

critically, radiation oncologists moved on to other emerging technologies,

such as three-dimensional conformal radiotherapy. Few people wanted to

associate themselves with what was perceived as a dead or dying field.

Once again, Germany and its neighbors lead the way. While Americans largely

deserted the field, the Germans learned from the failed trials and continued

to improve their equipment and their study designs. Last year the Dutch Deep

Hyperthermia Trial found that radiation plus hyperthermia improved overall

survival compared to radiation alone (51 percent vs. 27 percent at 3 years)

for patients with locally advanced cervical cancer. It was a hugely

important finding-demonstrating in a rigorous way that hyperthermia does

indeed significantly increase (in fact, nearly double) survival in a major

form of cancer.

a van der Zee, MD, PhD, is a Dutch leader in the field. She uses

hyperthermia to treat cervical, breast, and head and neck cancers, as well

as melanoma. They also believe it will also work in rectal and vaginal

cancers. Van der Zee reflects the widespread European belief that

hyperthermia should be used more often than it is now.

" With all the efforts to find new treatments that are more tumor selective

and less toxic, it is astonishing that an existing treatment that is

relatively tumor selective, has a low toxicity, and that in clinical studies

has been shown to result in considerable benefit receives so little

attention, " she said.

The American immunologist, Repasky, PhD, went even further,

raising the possibility of using hot baths saunas to raise temperatures in

conjunction with standard therapies. (One origin of hyperthermia was the

once-popular " Schlenz bath " of the 1930s and 1940s.)

Repasky has evidence from animal studies that mild heat improves natural

immunity to cancer as well as immune function. Perhaps, she told JNCI,

fever-range heat or a hot tub may provide some benefit to cancer patients

about to receive chemotherapy or radiation.

" Now wouldn't offering patients a sauna be a nice, patient-friendly adjuvant

therapy? " she asked. " We have a lot to be excited about in this field. "

There are important lessons to be gained from this history of hyperthermia.

One of them is that you should never rule out a therapy because of one or

two negative randomized controlled trials (RCTs). Oftentimes there are flaws

in the methodology or conduct of these trials that leads to negative

results. In the case of hyperthermia, it took the sympathetic and

intelligent guidance of Rolf Issels, et al., to finally show the power of

this " patient-friendly " modality.

--Ralph W. Moss, Ph.D.

References:

Stahl R, Wang T, Lindner LH, et al. Comparison of radiological and

pathohistological response to neoadjuvant chemotherapy combined with

regional hyperthermia (RHT) and study of response dependence on the applied

thermal parameters in patients with soft tissue sarcomas (STS). Int J

Hyperthermia. 2009 Jun;25(4):289-98.

Emami B, C, CA, et al. Phase III study of interstitial

thermoradiotherapy compared with interstitial radiotherapy alone in the

treatment of recurrent or persistent human tumors. A prospectively

controlled randomized study by the Radiation Therapy Group. Int J Radiat

Oncol Biol Phys. 1996 Mar 15;34(5):1097-104.

CA, Pajak T, Emami B, Hornback NB, Tupchong L, Rubin P. Randomized

phase III study comparing irradiation and hyperthermia with irradiation

alone in superficial measurable tumors. Final report by the Radiation

Therapy Oncology Group. Am J Clin Oncol. 1991 Apr;14(2):133-41.

Twombly R. International study of hyperthermia spurs hope in U.S. advocates.

J Natl Cancer Inst. 2010 Jan 20;102(2):79-81.

----------

No virus found in this outgoing message.

Checked by AVG - www.avg.com

Version: 8.5.435 / Virus Database: 271.1.1/2687 - Release Date: 02/14/10

07:35:00