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It has been reported that various types of immunoactivators can induce Graves' disease. We describe here a case of Graves' disease during treatment with sizofiran, an immunoactivator. A 42-year-old woman who had previously been in an euthyroid state with Hashimoto's thyroiditis, experienced thyrotoxicosis during continuous administration of sizofiran as immunotherapy for endometrial carcinoma. Since the TSH receptor-antibody was positive, and a thyroid scintigram showed diffuse goiter and high uptake, she was diagnosed as having Graves' disease. It is suggested that the administration of sizofiran may be one of the triggers of Graves' disease.

Clinical effects of doxifluridine (group A, 600 mg/body/day; group B, 800 mg/body/day) combined with radiotherapy and immunotherapy were evaluated in patients with advanced cancer of the uterine cervix. Response rates were 84.2% (16/19 patients) in group A and 100% (18/18 patients) in group B, respectively (p=0.230). There was no significant difference in adverse reaction incidence between the methods but significantly higher grade adverse reaction were observed in group B than in group A (p=0.048). Time to progression (TTP) was longer in group B than in group A (p=0.081). The optimal 5'-DFUR dose was 800 mg/body (group B), by which higher grade adverse reactions were fully controlled and TTP was prolonged.

Sizofilan (SPG), a simple glucan produced in a culture medium by Schizophyllum commune Feries, was used as an assistant immunotherapy in 15 patients with head and neck cancer. The cumulative 5-year survival rate was 86.7% in the SPG-treated group and 73.4% in the control group. Immunological parameters showed that the SPG group quickly recovered the cellular immunity damaged by radiation, chemotherapy and surgical procedure. SPG was found to be effective as an assistant immunotherapeutic agent in the treatment of head and neck.

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group. The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p = 0.074; generalized Kruskal-Wallis, p = 0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Kruskal-Wallis, p = 0.045). No side effects attributable to SPG were recorded. The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.

Adjuvant immunochemotherapy using the antitumour polysaccharide sizofiran (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed randomly for 386 Japanese patients with resectable gastric cancer. Although the overall survival probability for 5 years did not differ between the SPG and control groups, in 264 patients with curatively resected cancer, the probability to 5 year survival and to recurrence in the sizofiran-administered patients was better than in the controls. In the multivariate analysis, four of six prognostic factors correlated with the prognosis of the 264 patients who underwent curative surgery, that is, nodal involvement (chi 2 = 21.426, P = less than 0.0001), age distribution (chi 2 = 9.262, P = 0.010), sizofiran administration (chi 2 = 6.507, P = 0.011), and primary tumour size (chi 2 = 9.345, P = 0.025). Thus, patients with a curatively resected gastric cancer had a better prognosis when sizofiran was prescribed in combination with antitumour drugs.

To evaluate the clinical effects of the anti-tumor polysaccharide Schizophyllan (SPG), a randomized study was done on 220 patients with Stage II or Stage III cervical cancer who had been given irradiation, concomitantly. The tumor-reducing effect of SPG was significant in patients in either stage. The time to recurrence was longer in SPG-dosed patients with Stage II cancer, compared with findings in the control group. There was no significant difference in the time to recurrence in patients with Stage III cancer between the SPG and control groups. When comparing the 48-month survival curve, the survival time of patients with Stage II cancer in the SPG group was significantly longer than in the control group. However, there was no significant difference in the survival rate of patients with Stage III cancer between the SPG-dosed and control groups.

To clarify the clinical efficacy of SPG, a beta-1, 3 glucan extracted from cultured Schizophyllum commune Fries, a randomized comparative study was performed in combination with mitomycin C+5-fluorouracil (MF protocol) or tegafur (F protocol). A total of 514 cases with inoperable or recurrent gastric cancer were randomly allocated to either the SPG group or the control group, 367 of which were finally assessed for clinical efficacy. SPG was intramuscularly given at a dose of 20 mg twice a week or 40 mg once a week. Significant prolongation of life span was confirmed in the SPG group (MF protocol: p less than 0.01, F protocol: p less than 0.05), although the combination of SPG did not demonstrate a remarkable antitumor effect in both MF and F protocols. Among immune response parameters tested, the positive reactions in the PHA skin test were maintained in the SPG group and decreases in lymphocyte counts were inhibited by SPG in the MF protocol. Side effects associated with SPG therapy were noted in 6 of 258 cases treated with SPG. From these results, it is indicated that the combination of SPG and the chemotherapeutic agents may be useful in treating patients with inoperable or recurrent gastric cancer.