picibanil and Digestive-System-Neoplasms

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.

Topics: Adjuvants, Immunologic; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascitic Fluid; Cisplatin; Combined Modality Therapy; Cytokines; Digestive System Neoplasms; Doxorubicin; Female; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Mitomycin; Patient Selection; Picibanil; Pleural Effusion, Malignant; Prospective Studies

The usefulness of UFTMO therapy (combined chemotherapy with UFT, MMC and OK-432) performed in 40 cases of recurring or advanced cancer of the digestive organs was investigated. According the response criteria by Koyama et al., of 40 eligible cases, the treatment was judged effective in 13, 2 CR and 11 PR cases with a response rate of 32.5%, while of the 35 complete cases, 2 CR and 9 PR cases made for 11 effective cases and a response rate of 31.4%. Side effects were observed in 58.3% of the 36 evaluated cases; of the subjective and objective side effects, however, none were serious enough to require cessation of administration, while stopping administration in the cases of abnormal laboratory findings resulted in rapid recovery. UFTMO therapy, therefore, is considered to be one of the beneficial treatments for recurring or advanced cancer of the digestive organs.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Digestive System Neoplasms; Drug Evaluation; Female; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasm Recurrence, Local; Picibanil; Remission Induction; Tegafur; Uracil

The present study was designed to evaluate the effect of rTNF alone or in combination with other BRMs on human digestive organ cancers. Six kinds of human digestive organ cancer xenografts (esophageal, stomach, colonic, pancreatic, bile duct, and liver cancers: EC-YO, GC-YN, CC-KK, PC-HN, BDC-SN and Li-7, respectively) were transplanted in nude mice, and rTNF was administered at 10(3), 5 x 10(3), or 10(4)U/head directly into the tumor 3 times a week for 2 weeks. EC-YO was the most sensitive to rTNF, and intratumoral administration of rTNF at 10(3) U/head caused tumor regression. PC-HN, CC-KK and GC-YN were relatively sensitive to rTNF, and their growth was significantly inhibited by rTNF at 5 x 10(3) U/head, however, the tumors regrew after treatment. Li-7 and BDC-SN were resistant to rTNF. The effects of rTNF in combination with recombinant interferon-gamma (rIFN-gamma), recombinant interleukin-2 (rIL-2), or streptococcal preparation OK-432 were assessed in mice transplanted with GC-YN. All combinations of rTNF at 5 x 10(3) U/head and other BRMs were more effective than rTNF alone, and GC-YN tumors were completely regressed after treatment with a combination of rTNF and rIFN-gamma or rTNF and OK-432. However in all cases, the combination of rTNF at 10(3) U/head and any other BRM did not improve the effect. Furthermore, the adverse effects of the combinations were more serious than those of rTNF alone. TNF may still be a useful cytokine, because it can induce the regression of tumors. However, for its clinical application, a method should be developed to reduce its side effects.

Topics: Animals; Digestive System Neoplasms; Drug Synergism; Humans; Immunologic Factors; Interferon-gamma; Interleukin-2; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Picibanil; Recombinant Proteins; Transplantation, Heterologous; Tumor Necrosis Factor-alpha

A cytostatic factor was induced in the supernatants of human blood monocytes cultured in vitro with OK-432 at 0.01 KE/ml or more. This cytostatic activity was almost completely abolished by anti-human TNF antibody, and so was thought to be that of TNF. Recombinant human gamma interferon (IFN-gamma) alone did not induce TNF as described in other reports, but enhanced the induction of TNF by OK-432 when added to monocytes before or with OK-432. Monocytes of 20 patients with cancer of the digestive tract and 10 healthy donors were tested for ability to produce cytostatic activity. The frequencies of positive responses to OK-432 and the mean cytostatic activities of the two groups were similar. Moreover both groups included high responders whose monocytes produced potent cytostatic activity with OK-432 alone, and also low responders. Interestingly, marked synergistic effects of IFN-gamma and OK-432 were observed with monocytes that did not produce potent cytostatic activity with OK-432 alone. These results suggested that OK-432 may have a stronger immunomodulatory effect clinically when used in combination with IFN-gamma.

Topics: Biological Products; Cell Line; Digestive System Neoplasms; Dose-Response Relationship, Immunologic; Humans; Interferon-gamma; Monocytes; Picibanil; Recombinant Proteins; Tumor Necrosis Factor-alpha

The effects of intraperitoneal administration of OK-432 on tumor cells in ascites, in relation to the infiltration of effector cells and on the immune responses of the host, particularly, with regard to immune suppressive mechanisms, were investigated in 25 patients with cancerous ascites. The effects of OK-432 depended on frequency of the repeated and continuous administrations through a tube placed in the peritoneum during laparotomy. Infiltrations of neutrophils and lymphocytes were observed in the ascites within a short period after the administration and monocyte infiltration followed. Disappearance of tumor cells correlated well with the infiltration of these cells. No marked changes in the proliferative responses of peripheral blood lymphocytes were noted and decreases in serum inhibitory factor levels in sera were observed in patients given larger doses of OK-432. A marked reduction in Concanavalin-A-induced suppressor cell activities was observed after OK-432 administration. OK-432 administration probably leads to a disappearance of tumor cells by enhancing peritoneal effector cell activities and by inhibiting the induction of suppressor cell activities, in a dose dependent manner.

Topics: Ascites; Biological Products; Digestive System Neoplasms; Humans; Injections, Intraperitoneal; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes; Picibanil; Stomach Neoplasms; T-Lymphocytes, Regulatory; Time Factors

We have previously reported the clinical effects of NF therapy (NCS + 5-FU) and NFO therapy (NCS + 5-FU + Picibanil) on patients with advanced carcinoma of the digestive organs. In the present study, (NHO therapy (NCS + HCFU + Picibanil) performed in 41 patients and 30 patients were evaluated for its clinical effects. In comparison with NHO, NF and NFO, partial regression (tumor regression exceeding 50%) was noted in 5 of 30 patients (16.7%) on NHO, which was superior to 7.4% on NF, but slightly inferior to 18.8% on NFO. However, six and twelve month survival rate and 50% survival month on NHO therapy were 31.6%, 10.5% and 4.6 months, respectively and they were superior to those of NF and NFO therapy. Though the incidence of the adverse effects by NHO was almost identical with that of NFO and not more frequent than that of NF therapy. Urinary frequency, hot sensation and urgency due to HCFU administration were observed approximately in 10% on NFO therapy. In the three modalities the advantageous clinical effects on patients with hepatic carcinoma irrespective of primary or metastatic were observed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Digestive System Neoplasms; Drug Administration Schedule; Female; Fluorouracil; Humans; Male; Middle Aged; Picibanil; Zinostatin

Topics: Aged; Biological Products; Digestive System Neoplasms; Female; Humans; Injections, Intradermal; Injections, Intramuscular; Male; Middle Aged; Picibanil

Fifty-one patients with recurrent carcinoma of the digestive tract received immunotherapy consisting of the streptococcal preparation OK-432 in combination with FT207. In these patients, the following tests were carried out, peripheral blood leukocyte count, lymphocyte count and percent T-cell population of lymphocytes, delayed hypersensitivity skin tests with PPD, phytohemagglutinin and polysaccharide extracted from Su strain of Streptococcus pyogenes and serum titer of agglutinin to Strep. pyogenes. The results were statistically analyzed and correlated with the rate and duration of survival in order to re-evaluate the immunological parameters commonly used at present in anticancer immunotherapy. With respect to the peripheral blood leukocyte count, lymphocyte count, delayed hypersensitivity skin tests and serum titer of agglutinin to Strep. pyogenes assessed at 2 months of treatment, patients showing normal values or positive results had a significantly greater survival rate compared with those showing abnormal values or negative results. The peripheral blood lymphocyte count, delayed hypersensitivity skin tests and serum titer of agglutinin to Strep. pyogenes correlated significantly with survival. Particularly, the Su-PS skin test and serum titer of agglutinin to Strep. pyogenes showed remarkable correlation (P less than 0.01) with the survival rate and period.

Topics: Adult; Aged; Agglutinins; Digestive System Neoplasms; Humans; Immunity, Cellular; Leukocyte Count; Lymphocytes; Middle Aged; Picibanil; Skin Tests