Combination therapy of single or fractionated X-rays and Sizofiran for murine B-16 melanoma

B-16 melanoma transplanted into C57 BL/6 mice was used to investigate the antitumor effect of Sizofiran (SPG) combination with local irradiation by X-ray using 4 fractions of 3 Gy or 9 Gy and single fractions of 12, 19 and 26 Gy. In the groups which received a single fraction of 26 Gy and 4 fractions of 9 Gy, significant differences were found between the groups with/without SPG in terms of tumor volume change and lymph node and pulmonary metastases. In terms of survival, a significant difference was found only in the 4 fractions of the 9 Gy group. SPG had neither antitumor effect or life-prolonging effect, when it was applied to tumors irradiated with single fractions of 12 and 19 Gy or 4 fractions of 3 Gy, except for some metastasis-suppressing effect in the group given 19 Gy. The number of tumor cells eradicated by host-mediated immune response enhanced by SPG was estimated from tumor regrowth curve to be about 106 cells. The number is very close to that in the previous report for the combination therapy with pions and SPG. Therefore, the extent of the augmentation of the immune response by SPG after irradiation seems to be limited and idependent of the LET of radiation. From the metastasis-suppressing effect of SPG after X-ray irradiation, the gain produced by host-mediated immune response seems to be larger in the 4 fraction group. Therefore, combination radiotherapy using SPG may be advantageous for patients with complete response or a good partial response after multifractionated irradiation. (author)