Yasunori Nishio

Phase II study ofcis-diammine(glycolato)platinum, 254-S, in patients with advanced germ-cell testicular cancer, prostatic cancer, and transitional-cell carcinoma of the urinary tract

SummaryA multicenter cooperative study was conducted to evaluate the clinical efficacy and safety ofcis-diammine(glycolato)platinum (254-S), a second-generation anticancer platinum complex, in the treatment of genitourinary cancers. 254-S was given i. v. at 100 mg/m2 at 4-week intervals. As a result, 2 complete responses (CRs) and 8 partial responses (PRs) were obtained in 35 patients with transitional-cell carcinoma (TCC) of the urinary bladder or pyeloureter, 3 PRs were obtained in 16 subjects with prostatic cancer, and 6 CRs and 6 PRs were obtained in 15 patients with testicular cancer, generating objective response rates of 28.6% [95% confidence interval (CI), 14.6%–46.3%], 18.8% (95% CI, 4.0%–45.6%), and 80.0% (95% CI, 51.9%–95.7%), respectively. Bone marrow suppression was the dose-limiting toxicity, although it was reversible. Although no hydration was performed in approx. 40% of the patients, the incidence of nephrotoxic effects was low and most of those encountered were mild, the exception being one patient who showed severe renal insufficiency after the first treatment. Nausea and vomiting occurred in approx. 70% of the patients, but most gastrointestinal toxicities were controlled without antiemetic treatment. In addition, liver-function impairment was rarely observed. We conclude that 254-S is a promising cisplatin analogue for the treatment of genitourinary cancers and is worthy of further investigation in large-scale, randomized comparative studies with other platinum derivatives in both single-agent and combination regimens.

Adenocarcinoma of urachus report of 7 cases and review of literature

Seven cases of adenocarcinoma of the urachus treated at the National Cancer Center Hospital, Tokyo, over a nineteen-year period are reported. One hundred fifty-five cases reported in English literature and 140 cases in Japanese literature were analyzed with respect to the modalities of treatment, mean remission times, and sites of recurrence or metastases. From this review and experience on the 7 cases reported here, extended radical total cystectomy with well-designed radio- and chemotherapy was proposed for the treatment of this disease.

Significance of carcinoma in situ and dysplasia in association with bladder cancer

Cystectomy specimens of 118 transitional cell carcinomas of the bladder were analyzed by step-sectioning. The carcinoma in situ and dysplasia adjacent to and remote from the visible bladder cancer were correlated with the tumor configuration on cystoscopy, and grade and stage of the disease. Results showed that a combination of papillary and nodular carcinomas in a single bladder was associated with a high incidence of mucosal involvement. Moreover, more than 50 per cent of all grade 3 carcinomas were associated with carcinoma in situ and dysplasia adjacent to and remote from the visible tumors. Carcinoma in situ and dysplasia were not related to the stage of disease. For management of bladder cancer, it appears important to assess the gross configuration of tumors by cystophotography and to determine the grade of tumors by biopsy, because mucosal involvement was found to be correlated closely with the tumor configuration and grade 3 disease.

Effect of recombinant granulocyte colony-stimulating factor (rG-CSF) on chemotherapy-induced neutropenia in patients with urogenital cancer.

SummaryThe effects of recombinant granulocyte colony-stimulating factor (rG-CSF) on the myelosuppression, especially neutropenia, induced by cancer chemotherapy in patients with urogenital cancer were investigated in a randomized, controlled clinical study. In this study, rG-CSF was given subcutaneously at a dose of 2 μg/kg per day for 14 consecutive days. Changes in neutrophil counts were compared between the first (no rG-CSF) and second cycles (rG-CSF treatment period) of chemotherapy. rG-CSF administration was found to be effective in reducing the duration of neutropenia, in elevating the neutrophil nadir, and in reducing recovery time. Based on comparisons between the randomized rG-CSF treatment group (with rG-CSF) and the control group, treatment with rG-CSF resulted in the moderation or prevention of neutropenia and the acceleration of recovery. These results demonstrate that in chemotherapy of patients with urogenital cancer, in which neutropenia is a dose- or schedule-limiting factor, the concomitant use of rG-CSF may enable an increase in the dose (higher single dose or increased dose per unit of time) or shorten the chemotherapy period.

Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis.

The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six‐week‐old male Fischer 344 rats were given drinking watar containing 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine for 4 weeks. Following this 4‐week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti‐tumor‐promoting effect on rat bladder carcinogenesis.

Analysis of 90 Step-Sectioned Cystectomised Specimens of Bladder Cancer

For systematic understanding of papillary superficial carcinoma and nonpapillary invasive carcinoma of the bladder 90 cystectomized specimens of transitional cell carcinoma of the bladder were analyzed by step-section. From gross and microscopic observations bladder cancer was classified into 3 types: type 1--multiple papillary superficial carcinomas with or without small areas of dysplasia or carcinoma in situ, type 2--multiple coexistent papillary and nonpapillary carcinomas with widespread dysplasia and carcinoma in situ, and type 3--solitary nonpapillary invasive carcinoma without dysplasia and carcinoma in situ. Actuarial 5-year survival rates for types 1 to 3 were 97, 50 and 17 per cent, respectively. Although this classification is somewhat overlapping and there is a bias that basic data are obtained from the cystectomized specimens, we believe that such an analysis is necessary for considering the histogenesis and progression of human bladder cancer.

VAB-6 Chemotherapy Causes Spurious Elevation of Alpha-Fetoprotein Associated with Liver Dysfunctions

In order to elucidate the mechanism of elevation of alpha-fetoprotein (AFP) which we often observed during VAB-6 chemotherapy, we analyzed sequential changes of AFP, liver enzymes and bilirubin in 10 patients with evaluable disseminated testicular cancer who were treated with VAB-6 chemotherapy. None of the patients had previous liver disease or hepatic involvement. During the early phase of each course of chemotherapy, AFP showed a temporary elevation associated with reversible increase in liver enzymes and bilirubin. These changes returned to normal before the next course of chemotherapy. In each patient, marked tumor regression occurred as a result of VAB-6 chemotherapy. Nine of the 10 patients remain free of disease after treatment. We conclude that during VAB-6 chemotherapy, a temporary elevation of AFP is common, associated with reversible liver dysfunctions, and that this spurious elevation of the tumor marker, most likely caused by a heavy dose of cisplatin, should not be interpreted as related treatment failure.

Treatment of carcinoma in situ by total cystectomy: Histopathological analysis

SummarySeventeen specimens of primary or secondary carcinoma in situ (CIS) obtained by cystectomy were examined by step-sectioning. The posterior and lateral walls were mainly affected and 53% of the specimens showed invasion. Cases with a past history of superficial bladder cancer showed a particularly high incidence of invasion. Varieties of biological behavior of CIS are discussed.

Multidisciplinary Treatment of Invasive Bladder Cancer

To improve cure rates of locally invasive bladder cancer patients, we have performed radiation therapy prior to radical cystectomy in 88 patients since 1980. Until 1984, a total dose of 40 Gy for 4 weeks had been irradiated to the pelvic cavity of 46 patients, while 24 Gy with or without hyperthermia for 2 weeks has been applied to 42 patients since 1985. The treatment efficacy was assessed histopathologically according to the evaluation system proposed by Shimosato et al. in 1971. Approximately 50% of the patients responded well to this preoperative therapy. Among these patients, those with pT3 lesion showed significantly favorable prognoses as compared with the same stage patients who did not respond to the radiation therapy. However, the survival rates of the other pT stage patients did not correlate with the responsiveness to radiation. These results suggest that pT3 stage patients are the best candidates for preoperative radiation therapy, while radical cystectomy alone is adequate for those with superficially invasive lesions. Systemic chemotherapy should be properly built into the treatment strategy for those with locally far-advanced bladder cancer.