- Hyperthermia + Radiotherapy
- Hyperthermia + Chemotherapy
- Hyperthermia + Radiochemotherapy
- The Future
Hyperthermia and chemoterapy
Hyperthermia can enhance sensitivity of tumor cells to several anticancer drugs, especially alkylating ones (cisplatin) (Hettinga et al.,1997; Rietbroek et al., 1997).
The extent of the enhancement ranges between 1.2-10 times. Nevertheless, beside drugs showing considerable interaction (mitomicina C, cisplatin, doxorubicina, mitoxantrone, melphalan, carmustine, bleomycin), vinblastine, vincristine and etoposide showed no synergism at all (Van der Zee; 2002). Generally speaking, interaction is only seen when the two treatments are given in close sequence.
CT+HT Biological rationale: mechanisms of chemosensitization by hyperthermia
The most important mechanism to explain chemosensitization enhancement is the improved uptake due to increased blood flow (figure 1) which enhances drug delivery and drug extravasation.
Certain chemotherapics are very sensitive to heat stimuli.
Several studies have indicated that the activation energies for heat chemosensitization are much smaller than those for heat killing or heat radiosensitization and they are related to the reaction rates and to the formation of reactive intermediates (Dewey 1984; Urano et al. 1991).
It has been also observed that drug resistant cell lines can again acquire drug sensitivity when the same protocol is performed in the presence of heat stimulus (Van der Zee, 2002) (figure 2).
CT+HT Clinical rationale: thermal enhancement for tumor control
The synergistic effect of hyperthermia and chemotherapy is quantified by the Thermal Enhancement Ratio, defined as:
In the table (figure 1) are reported the Thermal Enhancement Ratios for the most widely used drugs.
Studies are available illustrating phase II and phase III trials where hyperthermia is combined with chemotherapy (Wessalowski et al., 1998; Issels et al., 1995).
Several randomized clinical trials on the use of hyperthermia as an adjuvant therapy to chemotherapy have shown significant results.
A review of the principal clinical trials is listed in the histogram (figure 2).