Overview

Hyperthermia is heat treatment. The temperature of the tissue is elevated artificially with the aim of receiving therapeutic benefits. Hyperthermia is considered an adjunct to other treatments in this country, but has been recognized abroad as a stand-alone therapy as well, sometimes superior to chemo.

One problem with treating cancer successfully is the fact that cancerous cells are very difficult to target specifically. In most respects, they are like normal cells, and even if they are not, they can hide the differences. But malignant cells are reliably more sensitive to heat than normal cells. Raising the temperature of the tumor is one way to selectively destroy cancer cells.

There are two ways to do heat therapy. One is external, where devices like heating rods, microwaves, radiofrequencies, ultrasound, thermal blankets and lasers are applied to the body. The other is internal, where substances called pyrogens are administered to the patient in order to induce fever. (Viz also the page on Coley’s toxins for more on fever therapy.) As far as I can tell, pyrogens are used to some extent in Europe and China, while U.S. doctors favor external devices. (Some sources prefer to speak of "fever therapy" as opposed to hyperthermia which is defined as treatment that elevates the body temperature without increasing the set point of the hypothalamus.) Hyperthermia is usually classified as local, regional or whole body.

It has been known for many centuries that heat helps the body against cancer. Unfortunately, the enthusiasm of modern cancer research for this modality has been sporadic until recently. It has been the alternative health community that has kept the access open for patients, particularly in other countries. In the 1960s, some researchers confirmed that cancer cells are more vulnerable to heat than their normal counterparts. In the U.S., the hegemony of the three official modalities -- surgery, radiation and chemo -- lasted until the 70s, when hyperthermia was taken off the ACS blacklist (Unproven Therapies List). In late 70s and early 80s several trials had shown that hyperthermia combined with radiation produced superior results over radiation alone. However, a U.S. phase III trial subsequently did not confirm these results, and interest waned. Hyperthermia has since inhabited a strange in-between land of having its value recognized, and being used sporadically in some cancer centers, while ignored or underutilized by most oncologists around the country, and largely unknown to the public.

That situation is beginning to change. It has been admitted that the U.S. study which showed negative results in the past was flawed on account of inadequate equipment and quality assurance procedures. And recently, the results of three European and one American phase III trials have become available. All these trials were well controlled, showing that the use of hyperthermia in combination with radiation therapy results in superior tumor response, tumor control, and survival as compared with radiation therapy alone. Some studies have claimed three-fold improvement in results, and positive results have even been noted with very difficult cancers like brain, liver and advanced kidney. Hyperthermia is particularly suitable in treating small superficial tumors (within 7 cm under the surface).

Summary of benefits

The synergistic effects of hyperthermia combined with radiation have been studied the most. Hyperthermia has been used for the treatment of resistant tumors of many kinds, with very good results. Combined hyperthermia and radiation has been reported to yield higher complete and durable responses than radiation alone in superficial tumors. In deep seated tumors, the effect of combined treatment is still under research. One source says "An extensive clinical experience has been accumulated with hyperthermia as a radiation enhancing agent. In regions where the heat can effectively penetrate the lesion, the results have been impressive."

Another source claims that "in all clinical studies hyperthermia has been shown to improve local control to some extent and has never worsened it." Despite difficulties in increasing human tumor temperatures, recent clinical trials have shown that a combination of hyperthermia with radiation is superior to radiation alone in controlling many human tumors.

It is unfortunate that patients usually come to hyperthermia when other modalities have been exhausted. But even in these circumstances, hyperthermia allows re-radiating tissue that has already received the maximum dose. Rates of response in these patients is generally high (one source reports impressive 93%!). Hyperthermia is one way to overcome the radioresistance of tumor cells. It is possible to combine hyperthermia safely with further low dose radiation in situation where a radical dose has already been delivered.

In addition, there seems to be evidence that whole body hyperthermia provides a measure of protection against radiation-induced thrombocytopenia. (And experiments in mice have shown an increase in platelet count 8 days after the administration of hyperthermia. The current theory states that whole body hyperthermia induces platelet stimulating hormonal factors.)

Hyperthermia improves the therapeutic index of TBI (total body irradiation), not only by increased neoplastic cell kill, but also by inhibiting the expression of radiation induced damage to the normal cell population. Some have experimented with hyperthermia as part of BMTs. Whole body hyperthermia results in early engraftment during BMT (there is up to 4-fold increase in GM-CSF and a 15-fold increase in IL-3).

When it comes to chemotherapy, there are indications that some chemo can be potentiated by hyperthermia. This can, in some agents, increase toxicities and the incidence of damage associated with them at the usual doses, or it can be taken advantage of in the sense of getting the same results with lower doses of the drug. In combination with chemo, the type of drug, dose, temperature and time of administration all play a role. Vinca alkaloids and methotrexate exhibit only some additive cytotoxicity. AMSA and Ara-C are inhibited by higher temperatures. Doxorubicin and dactinomycin are potentiated if heat follows, but inhibited if heat precedes them. Synergistic, supra-additive effects between heat and drug have been observed in bleomycin, BCNU, cisplatin, cyclophosphamide, melphalan, mitoxantrone, mitomycin C, thiotepa, misonidazole, and 5-thi-D-glucose. Some agents not cytotoxic at normal temperature show cell killing abilities at higher temperatures: alcohols, amphotericin B, cysteine, cysteamine and AET. Drugs showing no enhancement are the antimetabolites (mixed results with 5FU and methotrexate) and taxanes.

One source says: "The increased effect seen by combining cytotoxic agents with hyperthermia is complex, but may be due to altered drug pharmakinetics such as increased solubility (e.g. nitrosureas and alkylating agents), altered plasma protein binding (e.g. cisplatinum) and activation of enzymatic processes (e.g. anthracyclines). The new agents interferon, TNF and lonidamine and some hypoxic cell sensitizers are all potentiated by heat." Hyperthermia can augment the cytotoxicity without increasing myelosuppression, and reverse drug resistance to chemo agents.

I am very excited to find out that "it has recently been recognized that hyperthermia may also provide additional advantages in regard to drug delivery, particularly when the drugs of their carriers are relatively large. It has been shown in several studies that the use of hyperthermia can enhance the delivery of monoclonal antibodies to tumors with resultant improvement in antitumor effects. The spread into tissues of liposome-carried chemo drugs increases considerably compared to that under normal temperature." And interesting information has emerged from hyperthermia studies that may become valuable in the future -- a certain heat shock protein seems to be expressed on the surface of malignant cells after hyperthermia, and is absent in normal cells. This creates the possibility that monoclonal antibodies can be designed to home in just on the malignant cells.

Hyperthermia is also an immune system enhancer, and very effective in providing pain relief, controlling bleeding, and useful in other conditions such as prostatic hypertrophy and psoriasis.