1. Isshin Hospital, 1-18-7 Kita-Ootsuka, Toshima-ku, Tokyo 170, Japan
2. Holistic Medical Clinic, 6th floor of Ootsuka-KY Building, 1-18-11 Kita-Ootsuka, Toshima-ku, Tokyo 170, Japan.
ABSTRACT
We use biological response modifiers (BRM), such as BCG, OK432, and interferon- (IFN- ), as a pyrogen and a cytokine inducer, and administer small dosages of anticancer drugs at the optimal time during the systemic hyperthermal state. We applied this modality to 34 advanced breast cancer patients with bone metastases which were unresponsive to chemotherapy or radiotherapy, and obtained a favorable prognosis.and enhancement of immunity in most cases.
Keywords:BRM, cytokine, immuno-thermo-chemotherapy (ITC)
INTRODUCTION
Recently, it has been reported that not only some chemotherapeutic agents, but also some cytokines such as IFN and the tumor necrosis factor (TNF), have a synergistic effect with hyperthermia. The spontaneous tumor regression brought on by a pyrexia reported by W. Busch (1866) suggests the importance of immunological reaction in a pyrexia, as well as in a mild systemic therapeutic hyperthermia (39-41° C). We use BRM as a pyrogen and a cytokine inducer, and administer small dosages of anticancer drugs at the optimal time during pyrexia. We have applied this modality since 1975, called BRM-induced systemic ITC (BRM-S-ITC), more than three thousand times to various cancers. This time we treated breast cancers with bone metastases.
MATERIALS AND METHODS
From Jan. 1979 through Jun. 1987, We treated 34 advanced breast cancer patients from other hospitals who had received chemotherapy, or radiotherapy due to bone metastases. The schedule for drug administration is shown in Fig. 1. One of three pyrogens (1-7 mg of BCG, IC, IT, 0.4-10.0 KE of OK432, IV, and 1-3x10 U of IFN-.., DIV) is injected into the patient. When the body temperature is elevated to 38.5 ° C, one of 4 anti-cancer drugs (5 mg of CDDP, 2 mg of MMC, 20 mg of ACM, or 20 mg of MTX) is used during one course of BRM-S-ITC. The body temperature reaches 39-41° C spontaneously for a few hours to more than one day. The useful period of hyperthermia depends on the patient's condition.
This BRM-S-ITC is repeated at most once a week until a favorable response is obtained. Its efficacy is monitered by tumor markers (CEA, CA15-3, TPA, ferritin, ALP isoenzymes, RNase, etc.), immune parameters (the number of T-cells, S.I., NK activity), and usual morphological examinations.
RESULTS
DISCUSSION
All cases were hypoimmune and, resistant to both chemotherapy ' erapy and radiotherapy, but a favorable prognosis was obtained by BRM-S-ITC.
The same effects were obtained in other cancers, and complete response cases were obtained by this modality, whereas only 1.0 U/ml of TNF was detected during this course. It is not possible that an individual BRM, small dosages of chemotherapeutics, or mild hyperthermia alone has such an appreciable effects. Recently it has been reported that some cytokines such as IFN and TNF have synergistic effects with hyperthermia in vitro.
The results suggest that even mild hyperthermia between 39° C and 41° C has a synergistic effect with small dosages of chemotherapeutic agents in vivo, and that BRM-S-ITC has immunological effects which cannot be obtained by extracoporeal systemic hyperthermia. BRM-S-ITC will be developed as an effective and safe comprehensive cancer therapy.
Figure 1. The schedule for drug administration
Figure 2. Immunity compared with before and 3 months after the therapy.
Gordon Research Institute
Dr. Garry F. Gordon