The concept of immunochemosurgery in gastric cancer

Abstract

To evaluate the effectiveness of adjuvant immunochemotherapy in advanced adenocarcinoma of the stomach, patients who had undergone radical subtotal gastrectomy for stage III gastric carcinoma were randomized to receive immunochemotherapy or not. For immunotherapy,Streptococcus pyogenes preparation (picibanil) was given intramuscularly every week, and for chemotherapy, either MFC (mitomycin C, 5‐fluorouracil, and cytosine arabinoside) regimen or FME (5‐fluorouracil and methyl‐CCNU) regimen was given. Immunotherapy was started at the fourth or fifth postoperative day and chemotherapy was started at the eighth to tenth postoperative day. To evaluate the immune status of patients, various immune parameters such as 1‐chloro‐2, 4‐dinitrobenzene (DNCB) test, T‐lymphocyte count, PHA‐ and concanavalin‐A‐stimulated lymphoblastogenesis, and antibody‐dependent cellular cytotoxicity (ADCC) activity were checked before surgery and 3–4 months postoperatively. One hundred and thirty‐eight patients were chosen for study during a 5‐year period. Seventy‐four patients received postoperative immunochemotherapy and 64 patients received no further anticancer therapy following their operation. All patients had been followed for at least 5 years since they underwent surgery. Survival rate and immune status were compared between the 2 groups. Patient characteristics and preoperative values for the immune status of the 2 groups were similar to each other. The 5‐year survival rate of the postoperative immunochemotherapy group was 44.6%, whereas that of the surgery alone group was 23.4%. The difference is statistically significant (p<0.05). All the postoperative values of immune parameters showed more favorable data in the postoperative immunochemotherapy group. Postoperative immunochemotherapy is no longer adjuvant, but is an essential systemic therapy to prolong patient survival and cure disease. This author proposes to use the termimmunochemosurgery instead of “surgery and adjuvant immunochemotherapy” for gastric cancer.

Clinicopathologic characteristics and prognostic factors in 10 783 patients with gastric cancer

“…To improve the prognosis, systemic treatment, such as immunotherapy or chemotherapy, is needed in the early postoperative period to kill the micrometastatic or remaining cancer cells after curative resection. We [11,12,48] have already reported the effectiveness of immunochemosurgery, that is, radical surgery followed by early postoperative adjuvant immunochemotherapy, in randomized prospective trials with stage III gastric cancer patients. Since the present study was carried out retrospectively and randomization was incomplete, the differences in survival rates according to modality of postoperative adjuvant therapy are not as conclusive as those in our previous study.…”

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

“…The survival of patients receiving immunochemotherapy with intradermal OK-432 and ACAs was significantly better than that of matched control patients given chemotherapy alone (Uchida and Hoshino, 1980). The survival of patients with gastric cancer, who were administered intramuscular OK-432 in addition to the adjuvant chemotherapy after gastrectomy, was significantly better than that of patients who received adjuvant chemotherapy alone (Kim, 1987); a statistically significant improvement of the survival rate after lung cancer surgery was seen in patients treated with OK-432 alone or OK-432 and chemotherapy in comparison with the patients who were treated with chemotherapy alone (Watanabe and Iwa, 1987); and, a post-surgical adjuvant immunochemotherapy with oral OK-432 and MMC + 5-FU derivatives after curative resection of the gastric cancer resulted in a significantly better survival in comparison with chemotherapy alone (Kyoto Research Group for Digestive Organ Surgery, 1992). The mechanisms responsible for the benefits of the combination of OK-432 and chemotherapy are unclear.…”

“…immunotherapy with streptococcal preparation, OK-432, has been reported to be very beneficial in controlling malignant effusion (Katano and Torisu, 1982;Inoue et al, 1993;Torisu et al, 1983;Kawagoe and Masuda, 1986). OK-432 is a preparation of Streptococcus pyogenes, type A3, and this agent has been used as an anti-tumour immunomodulator for gastric, lung and other cancers (Kimura et al, 1976; Tokai Cooperative Study Group for Adjuvant Chemoimmunotherapy of Stomach Cancer, 1981;Kim, 1987;Watanabe and Iwa, 1987;Maehara et al, 1992). The i.c.…”

Preoperative Immunostimulation with Propionibacterium avidum KP-40 in Patients with Gastric Carcinoma: A Prospective Randomized Study

“…Fur thermore, preoperative immunotherapy did not improve sur vival of patients suffering from gastric carcinoma. However, recent reports about repeated administration of immunostimulating Streptococcus pyogenes [11] or BCG (combined with chemotherapy) [14] present encouraging results. Accord ingly, postoperative readministration of P. avidum KP-40 (eventually combined with chemotherapy) should be consid ered.…”