A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study.

OBJECTIVE: To determine whether postoperative adjuvant chemotherapy confers a survival benefit on patients with esophageal squamous cell carcinoma undergoing radical surgery, we undertook a cooperative, prospective randomized controlled trial. METHODS: A total of 205 patients underwent transthoracic esophagectomy with lymphadenectomy at eleven institutions between December 1988 and July 1991. These patients were prospectively randomized into two groups (100 patients underwent surgery alone and 105 patients had additional two courses of combination chemotherapy with cisplatin (70 mg/m2) and vindesine (3 mg/m2). The two groups did not differ with respect to sex, age, location of tumor, and distributions of pT, pN, pM, or p stage. RESULTS: The 5-year survival was 44.9% in the surgery alone group and 48.1% in the surgery plus chemotherapy group. The relative risk was estimated to be 0.89 (95% confidence interval, 0.61 to 1.31) in the surgery plus chemotherapy group compared with the surgery alone group. No significant differences in survival were detected between the two groups, even with lymph node stratification. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and vindesine has no additive effect on survival in patients with esophageal cancer compared with surgery alone.

Synergistic antitumor activity of combination chemotherapy with mitomycin C and cisplatin against human gastric cancer xenografts in nude mice.

A new combined cancer chemotherapy regimen of mitomycin C (MMC) and cisplatin (DDP) showed synergistic antitumor activity against human gastric cancer xenografts St-40 and SC-1-NU in BALB/c nu/nu mice. The drugs were administered intraperitoneally at doses of 2 or 4 mg/kg for MMC and 3 or 6 mg/kg for DDP, respectively. To clarify the schedule-dependent antitumor activity of MMC and DDP against St-40 and SC-1-NU, different sequential therapies were conducted. Simultaneous administration of these agents showed the highest antitumor activity against SC1-NU among the three regimens used, whereas the sequence of MMC followed by DDP showed higher antitumor activity than the reverse sequence against St-40. The intratumoral concentration of platinum was significantly increased in St-40 treated with the sequence MMC to DDP, in comparison with the sequence DDP to MMC. The maximum tolerated dose (MTD) of this combination was 4 mg MMC plus 6 mg DDP per kg in all the combinations, and these MTDs were 2/3 of the corresponding values for their single use. Since this combination increased the antitumor activity of each single agent without any increase in their toxicity, it would appear to be useful clinically.

Phase II evaluation of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japanese Esophageal Oncology Group Trial.

Thirty-nine patients with advanced measurable squamous cell carcinomas were treated with two or more courses of 70 mg cisplatin/m2 on day 1 and 700 mg infused 5-fluorouracil/m2 on days 1-5 every 21 days. The overall response rate was 35.9 (95% confidence limits, 24.8-55.1%). Responses were seen in primary sites in the esophagus of five patients, in the lung of seven, the liver of one and the mediastinal lymph nodes of one. The average response duration was 3.5 (range 1-12) mo for patients who achieved partial response. The average survival time after the first administration was 9.5 mo for patients who responded to the treatment whereas, for those who did not, it was 5.6 mo. The major form of toxicity was myelosuppression and there were six patients with grade 3 toxicity and one with grade 4. The present study was designed to evaluate the effectiveness of combined cisplatin and 5-fluorouracil for advanced squamous cell carcinoma, and the results showed that it had a reasonable effect and might possibly be used as a postoperative chemotherapy because of its mild side effects.

Preoperative radioactive therapy for esophageal carcinoma. Randomized evaluation trial in eight institutions.

A cooperative, prospective, randomized study to evaluate the effectiveness of preoperative irradiation in curatively resected esophageal carcinoma was performed in 364 cases in eight institutions from August 1982 to November, 1983. Based on the survival curves, postoperative irradiation alone was superior to preoperative plus postoperative irradiation. Because of the progression of the disease and complications after operation, there were many inevaluable cases in this study. However, analysis revealed there was no bias caused by a greater number of unfavorable patients being selectively included in inevaluable cases in the postoperative irradiation only group. Our data question the value of preoperative irradiation being performed in addition to resection plus postoperative irradiation.

The bioavailability of calcium in spinach and calcium-oxalate to calcium-deficient rats.

We estimated the utilization of calcium in spinach and calcium-oxalate to calcium-deficient rats, and the effect of oxalic acid on absorption of dietary calcium by using calcium-deficient rats. The body weight gain of the calcium-deficient rats for 8 days receiving a calcium-deficient diet supplemented with raw-powdered spinach (R-sp), boiled-powdered spinach (B-sp), or calcium-oxalate (Ca-ox), and a control diet supplemented with oxalic acid (OX-C) were 4.8, 2.8, 4.9, and 5.1 g, respectively. The calcium content in the liver and kidney of the rats receiving R-sp, B-sp, Ca-ox, and OX-C diets significantly increased as compared with the calcium-deficient rats. Significant differences in the liver calcium levels were not observed among the rats receiving various additional diets, though the content in the kidneys of the rats receiving R-sp, B-sp, Ca-ox, and OX-C diets were 28.0, 21.5, 0.11, and 0.59 mg, respectively. An especially large amount of calcium was accumulated in the kidneys of the rats receiving R-sp and B-sp diets. The calcium concentration in the serum of the rats receiving Ca-ox and OX-C diets was higher than the calcium concentration in the serum of the R-sp, B-sp, and calcium-deficient rats. The calcium content in the left tibiae of the rats receiving Ca-ox and OX-C diets was higher than that of the rats receiving R-sp and B-sp diets. The breaking force of the right tibiae of the rats was highest in the OX-C group, and higher in the R-sp and Ca-ox groups than the breaking force of the right tibiae of the rats fed on B-sp diet. The alkaline phosphatase activity in the small intestines of the rats rose in the order of the R-sp, B-sp, and Ca-ox groups, although significant differences of the activity were not observed between the Ca-ox and the OX-C groups. The calcium retention of the rats receiving the calcium-deficient, R-sp, B-sp, Ca-ox, and OX-C diets was -18.5, 35.2, 25.6, 41.6, and 45.8%, respectively. About 35% of the calcium in the spinach was absorbed by the calcium-deficient rats, and oxalic acid depressed the calcium absorption in the rats.

[Changes in cellular immunity and their effect on pulmonary infections and prognosis after surgery of esophageal cancer patients].

In esophageal cancer patients, pneumonia in an early (20%) and a late (3.5%) period, pythorax except for leakage (8%) and pulmonary tuberculosis (1.4%) were observed characteristically through the post operative course. Changes in cellular immunity through the course were indicated with remarkable depression of PHA stimulation index (s.i.) and T cell number. The lowest values during 5-year survey were observed 2 weeks after surgery. Especially, cases with post operative pulmonary infections had low PHA s.i. and low T cell number for long time, different from cases without them. As regards T cell subsets, both helper T and suppressor T decreased dramatically early after surgery and helper T kept in low value for long time, in contrast to suppressor T returned to normal range gradually, and then H/S ratio also depressively changed. Therefore, suppressive immunity after surgery must result in pulmonary infections and cause critical conditions. Cases with well reacted lymphocytes indicated high 5 year survival rate (40%).

[An experience in the treatment of severe surgical infectious diseases with combination of antibiotics and human gammaglobulin (SM-4300)].

The human immunoglobulin (SM-4300), which was developed by Travenol Laboratories, Inc. U.S.A., was used with antibiotics on 12 cases of severe surgical infectious disease. The method of administration and the evaluation of clinical effect of gammaglobulin (SM-4300) were made based upon the criteria of the SM-4300 study group. The clinical evaluation of the effect was classified in 5 grades; excellent, good, fair, poor and unknown. Three types of administration dose schedules were employed. Severe surgical infections were 3 cases of postoperative pneumonia, 3 cases of sepsis with pneumonia, 3 cases of peritonitis, 1 case of cholangitis, 1 case of sepsis with perinephritis and 1 case of subphrenic abscess. Bacterial and immunological examination were also performed before and after the administration of SM-4300. Evaluable cases were 10 cases out of 12 cases. Clinical effects of the administration of SM-4300 were evaluated as excellent in 1 case, good in 3, fair in 2 and poor in 4.