Kenjiro Itoh

A study of survival in patients with stomach cancer treated by a combination of preoperative intra‐arterial infusion therapy and surgery

Since 1968, there have been 62 patients with stomach cancer seen in the First Department of Surgery of Chiba University. Treatment consisted of preoperative intra‐arterial chemotherapy and surgery. The chemotherapy entailed continuous infusion for 15 to 20 hours. The survival rates were analyzed with particular emphasis on the degree of serosal invasion of the stomach. The overall survivals at the end of 3 years were 54.2% for the treated patients, and 37.1% for the controls: and at the end of 5 years, 33.3% of the treated patients were living as compared to 29.7% of the control patients. In patients without serosal invasion, the survival rates were higher for those treated than for the controls for the first 2 years. At the end of 3 years, the 39 patients treated for serosal invasion had a survival rate of 46.8% vs. 29% in the controls: and at 5 years, 32.2% of the treated patients vs. 23.7% in the controls. The survival rates for the treated patients with cancerous infiltration of other organs were about the same as those for the corresponding control patients.

Clinical value of immunochemotherapy with OK-432 or PS-K for stomach cancer patients

A prospective clinical trial was undertaken in 121 patients with stomach cancer to compare immunochemotherapy with 5-fluorouracil and FT-207 combined with OK-432 or PS-K, immunostimulators, and plain chemotherapy with 5-fluororacil and FT-207. Of the 121 patients who received immunochemotherapy, 67 patients (group A) had undergone curative removal of the tumor. The other 54 patients had undergone non-curative tumor removal or had recurrence after non-curative tumor removal and they were divided into two groups (groups B and C) on the basis of lymphocyte reactivity induced with PHA. Although group A exhibited a significant increase in PHA-induced lymphocyte transformation and a trifling increase in lymphocyte counts, its survival rate within a 36 month period did not differ from that of the peer controls. Group B, composed of 21 patients showing improvement of PHA-induced lymphocyte transformation, significantly prolonged its survival compared to the peer controls. The survival of group C, composed of 33 patients showing a gradual drop in PHA-induced lymphocyte transformation, was not prolonged compared to the peer control patients; and they showed significant decreases in lymphocyte counts. The overall survival of group B and group C was not superior to that of the 48 peer controls.

Intensified cancer chemotherapy by induction of hepatic drug-metabolizing enzymes as a trial for the treatment for stomach cancer

Studies of an intensified chemotherapy of FT-207, combined with MMC, have been under way since April 1977 in the First Department of Surgery of Chiba University Hospital and five closely related hospitals. These studies were performed on 114 patients with curative stomach cancer. The 114 patients received intravenously 0.4 mg/kg and 0.2 mg/kg of MMC on the operation day and the next day, respectively, and then intravenously 800 mg of FT-207 daily from the 10th postoperative day until discharge, followed by oral administration of FT-207, 600 mg, for more than 1 year after discharge. The 114 patients were divided into two groups. Half of the patients received 100 mg of phenobarbital and 30 mg/kg of glutathione for the purpose of induction of hepatic drug-metabolizing enzymes (induction group). Significantly higher levels of serum 5-FU released from FT-207 were observed in the patients of the induction group when compared to those of the control group. However, there was no statistically significant difference in survivals at both 12 and 24 months after operation between both groups.

Value of lymphocyte reactivity induced by phytohemagglutinin in the treatment of malignant diseases

An improved micromethod for evaluating in vitro lymphocyte blastogenetic activity, a modification of the method of Park and Good, is devised and used in 111 stomach cancer, 34 colorectal cancer, and 22 breast cancer cases. Follow-up information on the lymphocyte blastogenetic activity levels was available in 28 stomach cancer patients after the clinically complete removal of the tumor. In 16 patients with early stomach cancer the lymphocyte blastogenetic level did not differ greatly from a control values from healthy volunteers. However, in 66 advanced stomach cancer cases, statistically lower levels were encountered. After the complete removal of the tumor in 28 stomach cancer patients, the lymphocyte blastogenetic values rose postoperatively. The lymphocyte blastogenetic levels in patients with curative colorectal cancer or curative breast cancer were significantly higher than those in patients with non-curative tumors.

In vitro sensitivity test of stomach cancer tissues by the use of metal grid method

Ninety-nine specimens obtained from 53 patients with stomach cancer were cultured for about 3 days by means of the stainless steel grid method. In vitro effects of antitumor drugs on the cancer cells were evaluated autoradiographically or biochemically using a liquid scintillation counter to measure the uptake of3H-thymidine. The radioactivity of the labeled tumor cells of both control fragments and fragments affected by drugs varied greatly among individual tumors. Therefore, the in vitro efficacy of antitumor drugs was represented as a comparison with that of control fragments. Positive correlation between in vitro tests and the clinical effects of antitumor drugs was observed in the specimens of 18 cases.

Intra-arterial cancer chemotherapy with combined anticancer agents

Thirty seven patients with malignant tumors of stomach, liver and limb have been treated pre- and postoperatively with intra-arterial regional infusion of combined antitumor agents including cytosine arabinoside, methotrexate and mitomycin C with supplemental use of 5-fluorouracil, vincristine, vinblastine and cyclophosphamide. Six out of 11 patients with an inoperable gastric cancer showed a favorable response. In an inoperable primary and metastatic liver cancer, seven out of 9 patients, showed marked improvements such as tumor regression, restoration of liver functions and decrease of jaundice. The mean survival time was 4.5 months and one patient is still alive after 25 months. In 17 cases with the preoperative infusion, histological examinations of the tumors showed the marked degeneration of cells—the finding which seems to be superior to those otherwise obtained by single agent. The preoperative infusion of3H-thymidine followed by autoradiography of removed specimens did not show the uniform labeling of tumor cells. The radioactive labeling occurred throughout the tumor in most cases of gastric cancer and limb tumor. A major complication was leukopenia, which was observed in 13 out of 37 patients studied.