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It is generally difficult to treat patients with ovarian cancer. A Tenckhoff catheter was implanted in eighteen patients for intraperitoneal chemotherapy and drainage of ascites. Sixteen cases including 5 recurrent cases were treated with anticancer drug. It could not be used in two cases by bowel adhesion, so immediately catheters were removed. CDDP (100-150 mg/body) with or without Etoposide (180-300 mg/body) in 2 liters of saline was administered via Tenckhoff catheter over 30 minutes with a dwell time of 4 hours. We have studied the kinetics of CDDP and Etoposide in ascites and blood after intraperitoneal chemotherapy. High concentrations of free-CDDP and Etoposide were reached for 4 hours in the ascites but concentrations in the blood varied. These results showed obviously high values and direct effects on the tumor cells in the abdominal cavity and the peritoneal clearance depended on the severity of carcinomatous peritonitis in each case. Twelve cases showed decrease, but 4 cases increase of ascites. Five recurrent cases and one patient of stage IV died. Seven cases are outpatients and the disease free duration of their ranges are from 1 to 24 months. Three patients are now under treatment. Intraperitoneal chemotherapy elicited only mild nausea, myelosuppression and no significant changes of renal function. No patients had signs of catheter infection and peritonitis. These findings suggested that a Tenckhoff catheter was valuable to treat and manage ovarian cancer patients with little side effect.

Nephrotoxicity is the major side effect of cisplatinum (CDDP) and it is often the dose limiting factor. We have studied the effect of urinastatin (US) to decrease the nephrotoxicity of CDDP administration. 28 patients with gynecological cancer treated by chemotherapy including CDDP (13 mg/m2 daily for 5 days) were assigned to two groups, the group with US (n = 14) and the group without US (n = 14). The former was added each 150,000 units of US before and after administration of CDDP. The BUN, serum creatinine (Cre), creatinine clearance (Ccr) and the excretion of beta 2-microglobulin (beta 2-MG) index and N-acetyl-beta-glucosaminidase(NAG)index were measured. The BUN, Cre and Ccr were within normal range during four cycles. However NAG index rose remarkably when CDDP was treated by CDDP. And the increase in NAG index, which reflect the magnitude of renal tubal damage, was less in the group with US than in the group without US. It was suggested that US had effects to reduce nephrotoxicity of CDDP in chemotherapy, and that we could treat patients by high dose CDDP.

A new platinum coordination complex, l-OHP [oxalato (1R, 2R-cyclohexanediammine) platinum (II)], has been shown to be an active anticancer agent in animals. In the present study comparisons of the effects on human ovarian carcinomas transplanted into nude mice (OCl-1-N, OS-4-N, OY-1-N) between l-OHP and CDDP, were investigated. l-OHP (6 mg/kg, 9 mg/kg) and CDDP (3 mg/kg, 6 mg/kg) were administered intraperitoneally in a schedule of every four days for three doses. Simultaneously the tumor size and the body weight were measured and the peripheral WBC and serum BUN were examined. The results were as follows: 1) The antitumor activity of l-OHP corresponded to that of CDDP in proportion to the Pt content and mouse LD50. 2) In l-OHP, there was no elevation of the BUN value and less decrease in body weight, but the peripheral leukopenia was more severe, although reversible. l-OHP is an active anticancer agent against xenografts in nude mice and is strongly recommended for clinical application.

In the present study, comparison of the therapeutic effects of CDDP and the analogues (CBDCA, 254S, DWA2114R and NK121) on human gynecological carcinomas transplanted into nude mice (uterine cervical cancer; UZ-1-N, endometrial cancer; UE-1-N, ovarian cancer; OCl-1-N, OS-4-N and OS-8-N) was made. CDDP (5 mg/kg), CBDCA (50 mg/kg), 254S (25 mg/kg), DWA (50 mg/kg) and NK121 (18 mg/kg) were administered intraperitoneally every four days at three doses. Simultaneously the tumor size and the body weight were measured and the peripheral WBC and BUN were examined. The results were as follows: 1) The administration of 254S caused a marked inhibition of the tumor growth against all xenografts into nude mice. 2) CDDP and CDDP analogues except 254S were not effective against UE-1-N, but in this xenograft antitumor activity of 254S was remarkable. 3) With 254S, there were a decrease in body weight and the peripheral leukopenia and the elevation of BUN level were more severe. Although 254S has severe side effects, 254S is seemed to be recommendable for the treatment of gynecological malignancies.

The BUN, serum creatinine, creatinine clearance and the urinary excretion of leucine aminopeptidase (LAP), alkaline phosphatase (ALP), beta 2-microglobulin (beta-m), and N-acetyl-beta-glucosaminidase (NAG), were measured in 21 gynecological cancer patients treated with CAPF (CPA + ADM + CDDP + 5-FU) to evaluate the sensitivity of these indices to renal tubular damage. After receiving CDDP almost all patients displayed an increase in excretion of beta-m but no urinary enzyme activities. However, NAG index (NAG activity/urinary creatinine) rose markedly in all patients. We concluded that NAG index is a valuable method in providing sensitive indices for detecting renal tubular damage caused by CDDP.

The antitumor effects of human recombinant TNF (PAC-4D) were examined on three human gynecological carcinomas transplanted into CD-1 nude mice (uterine cervical carcinoma: UZ-1-N; ovarian carcinoma: OCl-1-N and OS-4-N). PAC-4D was administered intratumorally at a dose of 1,000 U, 3,000 U or 10,000 U/head from day 0 to day 4. Tumor size, body weight and peripheral WBC were measured on days 0, 4, 8, 12 and 16 and histological studies were made on day 6. The results were as follows: With UZ-1-N, intratumoral administration of PAC-4D at doses of 3,000 U and 10,000 U/head caused a marked inhibition of the tumor growth. Similarly, antitumor activity of PAC-4D against OCl-1-N was remarkable at a dose of 10,000 U/head. The administration of PAC-4D at doses of 3,000 U and 10,000 U/head was not effective against OS-4-N. The histological changes of grade II A-B by Ohboshi-Shimosato criteria of response were observed in the tumor of the effective groups against PAC-4D. There were no influences on the body weight and WBC after administration of PAC-4D. Although tumor cells possessed different sensitivities to PAC-4D, PAC-4D is strongly recommended for the treatment of gynecological malignancies.

A case of advanced cancer of the vulva that was treated by cisplatin with good result, is reported. This case was adenocarcinoma of Bartholin gland, and the clinical stage was third stage. The method of administration was intravenous injection of cisplatin (150 mg/body) in hypertonic saline (3%) for the decrease of nephrotoxicity. After administration (450 mg/body), the tumor markedly reduced. Additional operation, one course of CDDP and irradiation were carried out. After discharge, there has been no sign of recurrence for one year and five months. In this case, we used CDDP in hypertonic saline to decrease the nephrotoxicity. During these courses, the nephrotoxicity was moderate. This shows that patients can be treated by higher-doses of cisplatinum by this method.