Sequential combination chemoimmunotherapy for various malignant tumors: clinical and laboratory results

A chemoimmunotherapy program designed on the bases of the results of animal experiments was designed for 139 patients with various advanced malignant tumors. The treatment regimen consisted of cyclophosphamide (CY) 200 mg intravenously on day 1, Vibrio cholerae neuraminidase (VCN) treated autologous tumor cells admixed with BCG 5 to 10 mg intradermally on day 4 and mitomycin C (MMC) 10 to 16 mg and 5-fluorouracil (FU) 500 mg intravenously on day 7, of each course. Thereafter, maintenance treatment was started on day 14 with tegafur (FT) 600 mg and immunostimulants, such as OK432, PSK or levamisole. In the group of patients with gastric carcinoma, as compared to historical control patients, this treatment significantly improved survival in those with stage III disease (p less than 0.02), stage IV disease (p less than 0.05) and recurrent or unresectable tumor (p less than 0.001). Immune reactivities as measured by PPD skin test and PHA lymphocyte blastogenesis increased slightly following the therapy. After completion of the treatment, cellular immunity to autologous tumor extract could be detected in vitro by macrophage migration inhibition technique in 12 of 42 patients. The relationship of immune reactivity before or after therapy to patient survival was examined. Analysis of survival curves according to PPD skin test showed significant prolongation of survival in patients with positive reaction as compared to those with negative response following the treatment.