[Chemical modifiers in radiotherapy].

The halogenated pyrimidine analogue bromodeoxyuridine (BrdU), which is incorporated into nuclei during DNA synthesis, has long been known to be a radiation sensitizer. Since 1965, BAR therapy (BrdU-antimetabolite-radiation therapy), in which BrdU was administered intraarterially as a radiosensitizer, has been applied to patients with malignant gliomas and the improvement in survival rate within two years has been reported. Recently, intravenous infusion of BrdU has prove to be sufficiently effective as a radiosensitizer and BrdU is still being utilized as a chemical modifier for patients with malignant gliomas. Misonidazole was developed as a hypoxic cell sensitizer and was expected to enhance the radiation response of malignant tumors. However, the clinical trial of misonidazole in patients with brain tumors showed little clinical benefit of this agent as a radiosensitizer, and therefore it is no longer used in the treatment of malignant gliomas. Synchronized chemoradiotherapy, in which alkaloid and alkyl agents are used to accumulate cells into the radiosensitive G2 and M phases, was developed for the treatment of malignant gliomas in 1976 and significant improvement in survival has been reported. However, phase II studies demonstrated that radiotherapy with alkyl agents such as BCNU and ACNU did not prolong the survival of patients with malignant gliomas as compared with radiotherapy alone, although they did increase the response rate. Since 1985, the Brain Tumor Interferon Study Group has clinically applied one of the biological response modifiers (BRM), interferon-beta (INF-beta) as a chemical modifier in patient with malignant gliomas. They have reported that the response rates in patients treated with ACNU + radiation and INF-beta + ACNU + radiation were 19.6% and 41.2%, respectively. Their results suggested that IFN-beta with ACNU was a promising regimen as a chemical modifier in radiotherapy for patients with malignant gliomas. In order to improve the rate of local control of malignant gliomas and to prolong the survival of patients, it is necessary to continue to seek effective chemical modifiers including BRMs, as well as to develop irradiation techniques.