Efficacy of radiation therapy was studied using human renal cell carcinoma strain (AM-RC-3) implantable in nude mice. Cobalt 60 gamma-ray was used dosage of 5 Gy, 10 Gy, 15 Gy and 20 Gy in single, localized exposures of subcutaneously implanted tumors of the lower right femoral region. Therapeutic efficacy was determined using the Battelle Columbus Standard and evaluation of histological changes based on National Cancer Research Institute (Shimosato's classifications). Conclusion based on the obtained data are as follows: I) The T RW/C RW ratio on the tumor growth curve was 42% or less for all dosage groups except the 5 Gy group; dosages other than 5 Gy are believed effective. The 15 and 20 Gy dosage were particularly effective and the respective groups had RW of 0.96 and 0.95. II) Although Grade IIa and IIb changes were observed in the 15 and 20 Gy dosage groups, respectively, two weeks after irradiation, four weeks after irradiation all groups exhibited microscopic tissue formations that could be considered regrowth of tumor cells. Determination of histopathological effectiveness two weeks after irradiation is thought most suitable. III) Radiation therapy is appropriate as an adjuvant treatment in cases of renal cell carcinoma and should be used in combination with other therapies.
Eight patients with untreated squamous cell carcinoma of the esophagus accompanying distant metastases who were treated by one to five cycles of chemotherapy consisting of Cisplatin and 120 hour infusion of 5-Fluorouracil were reported. Two patients showed complete response (CR), four partial response (PR), one minor response, and one no response. High response rate of 75% (6 of 8) was obtained. Radiation therapy was then administered to six of the patients. After definitive treatment, CR was obtained in four, and PR in two of the cases. However, relapses were noted in all four of the CR cases, with four at distant sites, and one locally. Five of the eight patients (62.5%) survived one year and two survived three years (25%). Two patients could not receive radiotherapy because of uncontrollable lung metastases or death from duodenal ulcer. Although the follow-up period is still short, the combined treatment of radiation and pre-radiation chemotherapy appears to be an effective treatment, and has made a major impact upon survival time in cases of disseminated esophageal carcinoma.
Direct action of lentinan (LNT) on tumor cells in an in vivo system was observed by scanning electron microscopy. LNT was injected intraperitoneally 7 consecutive days (0.1 mg/mouse/day) in to C3H/He mice along with MM2 ascitic carcinoma cells. MM2 tumor cells adhering to the peritoneal wall were examined every day until the day after the last LNT injection, and compared with cells of non-treated tumor bearing mice. On the day after the first LNT injection, LNT was observed as granulated material both on the tumor cells, which were degenerated and on the mesothelial cells, which were not changed. On the 7th day, almost all tumor cells were seen to be surrounded by many lymphocytes in the LNT-treated mice. Retention of ascitic fluid and fibrin deposition were almost the same as or less than in non-treated mice. From these results, it is suggested that direct action of LNT on tumor cells contributed to enhancement of antitumor immunity, although LNT did not have direct killing activity against tumor cells.
From February 1979 through May 1988, a total of 26 patients with adenocarcinoma of the prostate were treated with radiation therapy for the primary site. The actuarial 5-year survival rate was 59% for 14 patients with Stage C or less disease (A; 1 case, B; 2 cases, and C; 11 cases), and 10% for 12 patients with Stage D. The logrank test showed significant difference between these two groups (p less than 0.007). Rectal radiation injuries occurred in 2 cases (8%) at 7 months (grade I) and 6 months (grade II), respectively. From the analysis of local control and complication, optimum radiation dose ranged from 64.8 Gy to 68.4 Gy (TDF 100-106). In addition, optimum boost radiation field size with rotation technique (after whole pelvic irradiation of 40-45 Gy with anteroposterior opposing fields) ranged from 30 to 48 cm2.
From February 1979 through May 1988, a total of 26 patients with adenocarcinoma of the prostate were treated with radiation therapy for the primary site. The actuarial 5-year survival rate was 59% for 14 patients with Stage C or less disease (A; 1 case, B; 2 cases, and C; 11 cases), and 10% for 12 patients with Stage D. The logrank test showed significant difference between these two groups (p less than 0.007). Rectal radiation injuries occurred in 2 cases (8%) at 7 months (grade I) and 6 months (grade II), respectively. From the analysis of local control and complication, optimum radiation dose ranged from 64.8 Gy to 68.4 Gy (TDF 100-106). In addition, optimum boost radiation field size with rotation technique (after whole pelvic irradiation of 40-45 Gy with anteroposterior opposing fields) ranged from 30 to 48 cm2.
As a second line therapy after failure to previous therapies, a combination therapy with MPA 1,200 mg po and 5'DFUR 1,200 mg po daily was given to 31 patients with recurrent breast cancer. At a median follow up period of 18 months, the overall response rate was 42%. The response rates for bone and visceral lesions were still good for the second line therapy. Patients previously exposed to tamoxifen (24 patients), 5-FU or its derivatives (21) and/or adriamycin (18) had response rates of 42%, 33%, 33%, respectively. The median duration of response in responders was 10 months. The overall median survival for the entire series was 9 months after start of the treatment. Thirteen (81%) of 16 patients with bone lesions were relieved from their bone pain. It is of special interest that the pain relief was also obtained in 7 out of 10 NC/PD patients with bone lesions, resulting in much improvement of their performance status. Side effects included obesity 52%, edema of the leg 35%, diarrhea 16% and so on. One patient developed venous thrombosis of her lower extremities and 4 were suspected to have the same condition. Fifty-five % of the patients underwent dose reduction of MPA at the 5th month of treatment in a median. This combination therapy is useful for recurrent disease even in late stages, so long as close observation is made for the occurrence of thrombosis.
Chemoembolization using CDDP, VP-16 and lipiodol was carried out for 7 patients with hepatocellular carcinoma (HCC). CDDP/lipiodol, CDDP/VP-16, CDDP/lipiodol (lipiodol 2-10 ml, CDDP 1-2 mg/kg, VP-16 100 mg/body) and gelatine sponge were administered in that order through the catheter located in the proper, or right or left hepatic artery. Three patients underwent hepatic resection 38-50 days after this treatment. Complete necrosis of the tumor was recognized in the one case, although the portion of necrosis did not exceed 70% in large sized HCC as the diameter of more than 10 cm. In 4 unresectable cases the decreases in tumor size were observed by ultrasonography and computed tomography. The response was: 3 partial responses and 1 no change. One out of 4 cases could undergo hepatic resection 17 months after this treatment. Two patients are alive 20 months after this treatment, although one patient died of HCC after 25 months. Serious side effect was not observed.
Twenty-eight evaluable patients with disseminated measurable malignancies of the genitourinary organs except testicular cancer were treated with MVP-CAB, between May 1985 and June 1988. Chemotherapy was given at 3 to 4 week intervals, as follows. On day 1, methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg/body were administered. On day 2, cis-platinum 50 mg/m2, on day 1 to 3, prednisolone 20 mg/body were also administered. The administration of bleomycin and adriamycin were limited to 90 mg/body and 400 mg/m2. The median age was 59 years. The median follow-up duration was 11 months. The primary lesions were urothelial tract cancer (19 patients), malignant lymphoma (1 patient), renal cell adenocarcinoma, penile cancer, prostatic adenocarcinoma, and leiomyosarcoma (2 patients each). CR was observed in 2 patients, and PR in 11 patients with urothelial tract cancer. The overall response rate was 68% (13/19). The response rates in primary and metastatic lesions were 56% (5/9) in primary, 73% (8/11) in lymph node, 71% (5/7) in lung, 67% (2/3) in liver, and 20% (1/5) in bone. The median duration of survival in the responders was 13.5 months, and in the non-responders was 5 months. The 1 year survival rate by Kaplan-Meier method was 70% in responders. On the other hand, the longest survival time in non-responders was 9 months. Marked improvement of survival time was noted in the responders. PR was observed in 1 patient with malignant lymphoma, prostatic adenocarcinoma, and leiomyosarcoma in each. The main toxic effect of MVP-CAB was bone marrow suppression. Leucopenia (WBC less than 4,000/mm3) was noted in 24 patients (86%), and 16 patients (57%) had a WBC count nadir below 2,000/mm3. Thrombocytopenia (plt less than 10 x 10(4)/mm3) was noted in 10 patients (36%). However, there were no deaths due to the bone marrow suppression.
We investigated the clinical effects and toxicity of chemotherapy with Cisplatin (CDDP) for head and neck cancer as the third joint research project of the Tokai Meeting for Head and Neck Tumors. The cases were examined at the cooperating institutions from September 1986 to March 1988. The subjects were 93 cases consisting of 66 patients (intravenous infusion: 47 cases; intraarterial infusion: 19 cases) of PP therapy (CDDP + PEP), 16 cases of PF therapy (CDDP + 5-FU) and 11 cases of PPV therapy (CDDP + PEP + VCR). The regimens of PP therapy were: CDDP 50-100 mg/body x 1 day, PEP 5 mg/body x 5 days (i.v.), and CDDP 10-20 mg/body x 5 days, PEP 5-10 mg/body x 5 days (i.a.). In the regimen of PF therapy, CDDP 80-100 mg/body x 1 day and 5-FU 750-1,000 mg/body x 5 days were administered. In the regimen of PPV therapy, CDDP 80-100 mg/body x 1 day, PEP 5 mg/body x 5 days and VCR 1 mg/body x 1 day were administered. As a rule, two courses of each of the regimens were performed. The total dose of CDDP in intraarterial infusion of PP therapy was significantly less than in intravenous infusion. The major results were as follows: 1) Total response rate was 57.0% on the average, and this was not significantly different among the regimens. 2) The response rate of intraarterial infusion of PP therapy was as high as that for intravenous infusion in spite of the lower CDDP dose. 3) The response rate of oral cavity was significantly higher than that of nasal cavity and paranasal sinuses. 4) In the squamous cell carcinoma, the response rate of the well differentiated type was significantly higher than that of the poorly differentiated type. 5) The leukocyte counts significantly decreased with the intravenous infusion of PP therapy, PF therapy and PPV therapy. 6) The platelet counts significantly decreased with PPV therapy. 7) There were no significant changes with time with Ccr and PaO2 of PP therapy. 8) The frequency of toxicities such as nausea and vomiting was high in the intravenous infusion of PP therapy, PF therapy and PPV therapy. However, the frequency of toxicity was low in the intraarterial infusion of PP therapy.
Using a questionnaire, the urinary function of 68 patients and the sexual function of 81 patients were evaluated after rectal cancer operation. The patients with carcinoma of the rectum suffered from severe damage to the urinary system following Miles' operation (Miles) which included 85.7% of the male and 42.9% female. On the other hand, 31.8% male and 33.3% female suffered following anterior resection or pull through operation (AR). Following Miles 64.3% male and 71.4% female had developed urinary incontinence while 36.4% male and 33.3% female developed the same following AR. These results indicate that dysfunction of the urinary voiding system was more common in the males while the females experienced urinary incontinence. This difference may be due to the severity of the surgical intervention to the bladder neck and partly to the anatomical difference of pelvic floor and of urethra. The recovery was poor in the patients who had developed disorder of the urinary voiding system and unfortunately 84% patients following Miles and 75% patients after AR could not return to normal voiding even five years after operation. Urinary incontinence persisted after Miles and after AR in 77.8% and 31% patient respectively. Sexual activity was remarkably reduced following Miles. The males lost the power of erection and ejaculation, the females suffered due to the existence of artificial colostomy. In order to maintain the normal physiological activity of the urogenital system following operation, it is important to avoid any damage preferably to the bladder neck and urethra in case of males and to avoid artificial stoma in females.
In Omagari city and five towns, 37,793 women were subjected to mass screening of uterine carcinoma from 1979 to 1988. The detection rate of uterine carcinoma was 0.058%. Initial screening rate was 41% 10 years ago, but in 1988, it was decreased to 18%. The peak age of the mass screening was 50-54 years old, but the carcinoma and dysplasia high degree were detected mostly in patients aged 60 years old or more. And the constitution of the age of mass screening in this study was inadequate for the screening of endometrial carcinoma. It is important to emphasize that older women (aged 60 or above) and nullipara should be encouraged to actively participate in the screening of cervical and endometrial carcinoma.
In Japan where the question of cancer notification has yet to be resolved, it is difficult to obtain an informed consent from the patient himself in clinical studies of the chemotherapies for cancer. In fact, the chemotherapy is administered while not enough explanation is given to the family let alone the patient. Such is the present situation. For the purpose of finding out the best possible method at present, we carried out a method whereby an informed consent of the family is substituted for a consent of the patient in phase II study of inoperable non-small cell carcinoma of the lung. As a result, the consent was obtained from 21 (91.3%) out of 23 families. This method should be taken into consideration as a feasible one under the present circumstances. It was in only one family (4.3%) that a consent on the notification of diagnosis from the family to the patient was obtained. In order for the informed consent to be established, efforts to form a social consensus on cancer notification are needed.
One hundred and one cases of hepatocellular carcinoma (HCC) treated in Maebashi Red Cross Hospital from May 1984 to August 1987 were classified according to the therapy and progression of the disease and were investigated on their prognosis. Furthermore, "long survived group" in which, patients survived for more than one year were compared with "short survived group" in which patients died within one month after non-surgical treatment. In operated patients, the prognosis was the best, but the rate of operable cases was only 13.9%. In patients with stage IV, one year survival rate was significantly low. In patients with portal trunk invasion (Vp4), or with Child C that was the poorest functional reserve of the liver, one year survival rate was also significantly low in comparison with patients with other stages or other Child's classification. In HCC patients treated with transcatheter arterial embolization (TAE), the prognosis tended to be poor as stage and portal invasion progressed, but in regard to reserve function of the liver, the prognosis was not so poor in patients of Child C significantly as in cases of A or B. The comparisons between long and short survived group were as follows. a) In 17 cases belong to long survived group, mean survival period was 24 months and the longest one was 4 years and 10 months. On the other hand, in 10 cases belong to short survived group, mean survival period was 17 days, the shortest one was 3 days. b) The main reason of inoperability in long survived group was progression of the tumor. Complications such as diabetes mellitus, advanced age and rejection of treatment by the patient were the other reasons of in operability. In almost half of the patients in short survived group, the tumor progression and low functional reserve of liver were found in 4 patients. c) In short survived group, esophageal varices were more common and functional reserve of the liver was poorer than in long survived group. In short survived group, LDH and total bilirubin were significantly higher than those of long survived group, but there was no significant differences in transaminase value and ICG retention in 15 minutes. d) In short survived group, extent of the tumor in liver and portal invasion were advanced. Three cases of this group (30%) had distant metastasis. e) In long survived group, the main reason of death was hepatic failure. Renal failure, or pulmonary complications were also found in short survived group.(ABSTRACT TRUNCATED AT 400 WORDS)
Bone is one of the involved organs of distant metastasis in breast cancer. We examined bone metabolism by microdensitometry (MD) method in 94 patients with breast cancer (40 with bone metastasis and 54 without it) and 10 with benign breast diseases. There was no significant difference among the three groups in the background factors of menopausal status and hormone receptors status. MCI, GSmin, sigma GS/D and bone pattern by MD method in breast cancer patients with bone metastasis were significantly lower than those in the other groups. There were slight reverse correlation between sigma GS/D and serum ALP. MCI and sigma GS/D indices corrected by ages were also significantly lower in bone metastasis (p less than 0.01). These indices in most of the patients with bone metastasis gradually decreased as the lesion progressed. The results revealed that microdensitometric analysis of bone metastasis for breast cancer was of use for the diagnosis and evaluation of therapeutic effect in the follow-up study.
Four tumor markers (CA125, CA19-9, CEA, TPA) were analysed between the localizations and the serum data in the 36 ovarian cancers. The positive rates of each tumor markers were; 23 cases (63.9%) on CA125, 15 cases (41.7%) on CA19-9, 12 cases (33.3%) on CEA, and 27 cases (75.0%) on TPA. CA125 and CA19-9 were observed in the luminar borders and cellular membranes on serous adenocarcinomas and in the cytoplasms on mucinous adenocarcinomas. Both CEA and TPA were stained in cytoplasms. The correlation in the localization was observed between CA19-9s and CEAs (Kendall's rank correlation = 0.5303 greater than 0.5). The correlations between the localization and the serum data were observed on CA19-9 and CA125.
We examined the effect of concomitant use of anticancer drugs such as Carmofur or 5-FU and Nicardipine, a Ca2+ antagonist, on human gastric cancer transplanted into nude mice, and obtained the following results: 1. Combined administration of Carmofur or 5-FU together with Nicardipine caused potentiation of an antitumor effect. 2. After Carmofur was used together with Nicardipine, the FU level in the tumor tissue was significantly elevated. In conclusion, it was found that in the combined use of Carmofur or 5-FU together with Nicardipine, a Ca2+ antagonist, caused a higher level of the FU in tumor tissue and potentiation of an antitumor effect on human gastric cancer transplanted into nude mice.
From July 1973 to October 1983, 77 patients received mastectomy followed by postoperative irradiation at National Medical Center Hospital. The patients were classified as follows: 9 cases as stage I, 30 cases as stage II, 28 cases as stage IIIa, 7 cases as stage IIIb and 2 cases as stage IV. Irradiation fields were the parasternal and supraclavicular region. The axis of the irradiation fields to parasternal and supraclavicular regions were set up at 3.5 cm from the surface of the body and they were irradiated separately. The irradiation fields were about 0.5 cm apart from each other. Parasternal region contained bilateral parasternal lymphnodes. In some cases, the centersplit was used to prevent the radiation myelopathy. Prophylactic irradiation to axilla was performed by electron beam from October 1974 to September 1977. Prophylactic irradiation to chest wall has not been done since 1973. The five and ten years survival rates of stage II were 93.2% and 86.3%, stage IIIa were 61.9% and 55. 7%, Stage IIIb were 71.4% and 35.7%. The rate of the local recurrence at the supraclavicular region was 0% as stage I, 6.7% as stage II, 0% as stage IIIa and 14.3% as stage IIIb. Among the cases with regional lymphnode involvement at the time of mastectomy, the rate of local recurrence at the supraclavicular region was 6.7% in prophylactic irradiation group and it was significantly lower than in non-prophylactic irradiation group (11.5%) (p less than 0.05). The rate of local recurrence to chest wall was 0% as stage I, 6.7% as stage II, 8.0% as stage IIIa and 42.9% as stage IIIb.(ABSTRACT TRUNCATED AT 250 WORDS)
We devised new combination therapy of radiation and local administration of OK-432 and performed for 26 patients with esophageal cancer between March, 1987 and December, 1988 as a pilot study. The average age was 73 years. Among 26 patients, male were 20 and female were six. Patients were irradiated at the schedule of under 2 Gy/day and the dose of TDF (time, dose and fractionation factor) 100 totally. OK-432, 10KE was endoscopically administered around cancer lesion at the beginning of the radiotherapy, and two weeks later, 5KE was given in the same manner. Complete response was obtained 20 out of 26 cases (77%) and partial response was obtained in the remaining six cases (23%). All six patients with tumor length less than five cm showed complete response. All 16 patients who could not eat food orally before treatment, became to take food enough orally after the treatment and could discharge in good condition. One year and two years survival rate of 26 patients by Kaplan Meier method were 67.4% and 47.2%, respectively. Six patients with tumor length less than five cm, are all alive without a sign of recurrence. This combination therapy will improve not only the response rate and the survival rate, but also the quality of life of patients with esophageal cancer.
Recombinant interleukin-2 (rIL-2) was administered intraperitoneally for 15 days, 2 days after intraperitoneal administration of Streptococcal preparation OK-432 to a patient of peritonitis carcinomatosa occurred eight months after second look operation, in which residual tumor could not be removed completely. The patient had been maintained by hemodialysis three times a week for over ten years. Combination chemotherapy using CDDP and Ifosfamide, or CDDP and THP-Adriamycin had not been effective to control rapidly increasing ascites. Negative cytological exam, was achieved on day 7 and ascites disappeared by day 15. No severe side effects including fluid retention were observed. Fever up was controllable by Indomethacin. Flow cytometric analysis revealed dominant (73%) CD4+, CD29+ helper inducer subset, while CD4+, CD45RA+ was 6%, in the lymphocytes in ascites on day 8. It was suggested that intraperitoneal administration of rIL-2 after OK-432 was safe and effective for peritonitis carcinomatosa with chronic renal failure.
The present study was designed to determine the optimal dose and frequency of oral administration of a biological response modifier, OK-432 (Picibanil), which has been used for cancer immunotherapy by injection. Ninety one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40KE, once or 3 times a week before operation (5KE X 1/W, 20KE X 1/W, 40KE X 1/W, or X 3/W). Misregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. In the 1st report, we already showed that 5KE X 3/W might be the optimal regimen to augment the natural killer (NK) activity of regional lymph node lymphocyte (RNL). In the 2nd report, we searched for the optimal regimen to augment the antitumor immunity of T lymphocytes. The proliferative response of RNL to SuPR (protein derived from OK-432) was augmented in all the groups administered OK-432. The responsiveness of PBL to autologous tumor extract enhanced by IL-2 was augmented by 5KE X 1/W, and that of RNL was augmented by 5KE X 3/W. The killer/suppressor (Leu2+15-/Leu2+15+) ratio in RNL increased in all the groups administered OK-432 especially in 20KE X 3/W group. Oral administration of OK-432 augmented both non-specific and the specific antitumor immunity of PBL as well as RNL, and 5KE X 3/W may be the optimal regimen to augment the antitumor immunity, especially of RNL.
