The efficacy of adjuvant immunochemotherapy with OK-432 after curative resection of gastric cancer: an individual patient data meta-analysis of randomized controlled trials

Abstract

Background OK-432 has been used as a cancer treatment for 40 years, and the immunostimulatory effects of OK-432 therapy have been intensely investigated in Japan. Recently, it has received attention as a possible booster for cancer vaccine treatments. Our previous meta-analysis based on summary measures revealed a significant improvement in the survival of patients with curatively resected gastric cancer. However, it is impossible to exclude the possibility of bias due to several prognostic factors. Methods We collected individual data for patients with stage III or stage IV gastric cancer after curative resection from 14 trials that were identified in a previous metaanalysis. Immunochemotherapy with OK-432 was compared with treatment with standard chemotherapy on an intention-to-treat basis. The primary end point was overall survival. Stratified survival analyses were performed with the trial as the stratification factor. Subgroup analyses were also performed according to the potential prognostic factors, which included pathological factors, splenectomy, and delayed-type hypersensitivity. Results There were 796 and 726 patients in the OK-432 and control groups, respectively. The median overall survival was 42.6 months for the OK-432 group and 32.3 months for the control group. The overall hazard ratio was 0.88 (95 % confidence interval 0.77-1.00, p = 0.050). No factor showed a statistically significant interaction in the subgroup analyses. ConclusionsThe results suggest that immunochemotherapy treatment with OK-432 could have a borderline significant effect for patients with stage III or stage IV gastric cancer after curative resection.

Bacterial ghosts as adjuvant to oxaliplatin chemotherapy in colorectal carcinomatosis

“…39 Recently, several preparations of living, attenuated or genetically engineered bacteria (e.g. the streptococcal preparation OK-432 (Picibanil), 40 Listeria monocytogenes 41 or Salmonella typhimurium 42 ) were tested for anticancer therapy in human, with Bacillus Calmette-Gu erin even being used as first-line local immunotherapy of superficial bladder carcinoma 43,44 and OK-432 being approved for lymphangioma in Japan since 1995. 40 The molecular basis of the interaction between bacterial and immune cells are socalled pathogen-associated molecular patterns (PAMPs), like e.g.…”

Randomized phase III trial comparing surgery alone to UFT + PSK for stage II rectal cancer (JFMC38 trial)

“…With regard to locally advanced gastric cancers, a number of immunochemotherapy clinical trials combined mainly with oral fluorinated pyrimidine anticancer agents have been conducted. A borderline significant effect was demonstrated in randomized clinical trials as well as in a meta-analysis for PSK and OK-432 [ 9 , 10 , 15 , 16 , 15 , 16 ], although no significant effect of Lentinan was proven for advanced or metastatic gastric cancers in a recently published study [ 17 ]. Although PSK has shown somewhat favorable outcomes for colon cancer patients in adjuvant settings, initial studies for those agents failed to confirm their significant advantage, and they were eventually excluded from use in community practice in early development.…”

Meta-analysis of randomized clinical trials in the era of individual patient data sharing

“…However, a long and difficult process that can take several years and require a sophisticated organization is one of the limitations of prospectively obtaining IPD. Authors have been conducting retrospective IPD meta-analysis for over 15 years but it is also difficult and time-consuming to obtain IPD for a retrospective IPD meta-analysis [ 23 – 27 ]. Recently, however, data-sharing initiatives have been discussed in the medical literature [ 8 – 17 ].…”