Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion

Abstract

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. © 1999 Cancer Research Campaign

Efficacious pleurodesis with OK‐432 and doxorubicin against malignant pleural effusions

“…These antitumour effects may be due to an immunomodulatory property of OK-432, by activating neutrophils, macrophages, natural killer cells, or T-lymphocytes [21,22]. Further, activated mononuclear cells are known to produce a variety of cytokines including interleukin-6, thus resulting in augmentation of antitumour effects [7].…”

“…More importantly, OK-432 can be administered into the pleural or peritoneal cavity with anticancer agents. Simultaneous administration of OK-432 and one of the anticancer agents such as cisplatin, mitomycin C or doxorubicin achieved both a higher response rate and survival rate than that accomplished by any anticancer agent alone or OK-432 alone, according to the report of a randomised study for malignant effusions [7]. To date, there has been no prospective study conducted to evaluate the effect of pleurodesis with a combination of OK-432 and doxorubicin for malignant pleural effusions associated with lung cancer.…”

“…Pleurodesis with OK-432 has been reported to be efficacious for controlling malignant pleural effusions [5,6]. Moreover, a recent study suggests intrapleural injection of both OK-432 and an anticancer agent may be more beneficial than that of an anticancer agent or OK-432 alone [7]. There have been several reports using a combination of OK-432 and doxorubicin for controlling malignant pleural effusions in Japan including the authors9 study [5,[7][8][9].…”

“…Moreover, a recent study suggests intrapleural injection of both OK-432 and an anticancer agent may be more beneficial than that of an anticancer agent or OK-432 alone [7]. There have been several reports using a combination of OK-432 and doxorubicin for controlling malignant pleural effusions in Japan including the authors9 study [5,[7][8][9]. In the authors9 previous study, which was conducted in an uncontrolled and retrospective design in 67 individuals with pleuritis carcinomatosa, the combination of OK-432 and doxorubicin had achieved a high response rate of 85% [9].…”

Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus Interleukin-2

“…OK-432 is one of the most popular anticancer drugs and is the only agent approved for locoregional use in patients with malignant effusion in Japan (Nio et al, 1999;Gochi et al, 2001). It is a penicillin-and heat-inactivated lyophilised powder of Streptococcus pyogenes A3.…”