Of 133 patients with advanced urothelial tract cancer given methotrexate (MTX), vinblastine (VBL), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (DDP) (M-VAC regimen), significant tumor regression occurred in 72% f 8% of 121 with transitional cell carcinoma (TCC) evaluable for response. Complete remission (CR) was achieved in 36% +-9% of patients, of whom 11% required the addition of surgical resection of residual disease. Although 68% of CR patients have relapsed, CR median survival will exceed 38 months compared with 11 months for partial (36%) and minor (6%) responders, and 8 months for nonresponders: 2-year and 3-year survivals were 68% and 55%, respectively, versus 0% to 7% for the remaining patients. Sixteen percent of responders developed brain lesions, half of whom had no systemic relapse a t the time of progression. Three patients with non-TCC histologies did not respond. In 32 patients who had pathologic restaging, the clinical (T) understaging (T < pathologic [PI restaging) error was 35%. Although all metastatic sites showed evidence of tumor regression, CR was noted more frequently in lung, in intraabdominal lymph nodes and masses, and in bone (24% to 35%); the rate for hepatic lesions was 15%. There were 52% of 21 NS4& patients who achieved CR versus 33% of 100 with No.+M+ lesions. Toxicity was significant with 4 (3%) drug-related deaths, 25% incidence of nadir sepsis, 58% 2 3+ myelosuppression, and 49% with mucositis. Responsiveness of metastasis in various sites, patterns of relapse, and the usefulness of the new CR response criteria are reported, as is the current status of cisplatin and methotrexate combination regimens.Cancer 64:2448-2458, 1989. noma (TCC), complete remission (CR) was achieved in 37% of patients, with 55% alive from 26+ to 49+ months, and partial remission (PR) in 3 1 % of patients. The current Phase I1 study reports the experience of the first 3 years with a follow-up of a minimum of 3 years from patient entry (median follow-up is 54 months), the responsiveness of the primary tumor and metastases at different sites, the relapse patterns, and the accuracy of clinical staging. In 46 cases, serum MTX levels obtained on day 2 were within the expected range.'Patients were hospitalized for 3 to 5 days of each monthly cycle (Table 1) for diagnostic tests and hydration with D5 1/2NS with potassium supplement to assure a urinary output of >lo0 ml/h, and until the blood urea nitrogen (BUN) and creatinine (Cr) returned to pretreatment values. Generally, DDP was given with antiemetics and 12.5 g mannitol. ADR was reduced to 15 mg/m2 in patients who had irradiation equivalent to >20 Gy in 5 2448

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.

Of 92 patients who received methotrexate, vinblastine, doxorubicin and cisplatin complete and partial remissions were observed in 69 +/- 10 per cent of 83 adequately treated measurable and evaluable patients with advanced stages (N+M0 and N0M+) transitional cell urothelial cancer. Complete remission was achieved in 37 +/- 10 per cent of the patients clinically, pathologically and after surgical resection of residual disease. With 17 of 31 complete responders (55 per cent) surviving for 26+ to 49+ months, the estimated probability of survival at 2 and 3 years was 71 and 55 per cent, respectively. Partial remission occurred in 31 +/- 10 per cent of the patients, while 8 per cent had a minor response and 23 per cent had progression with median survivals of 11, 11 and 7 months, respectively. Whereas all metastatic sites responded, including the bone and liver, complete tumor regression was observed more frequently with nodal, pulmonary and local-regional lesions. Brain metastases occurred within 6 to 42 months in 18 per cent of the responders, half of whom never had systemic relapse. Of the remaining 9 patients 2 with nontransitional cell histological tumors did not respond, 5 (5 per cent) were inadequately treated and 2 were excluded from response data because of inevaluable disease parameters but they were free of disease at 16+ and 31+ months. Toxicity was significant, with 20 per cent of the patients experiencing nadir sepsis, 4 per cent a drug-related death, 31 per cent +1 renal toxicity and 41 per cent +1 mucositis. The applications and advantages of the newly proposed international response criteria for bladder cancer are discussed in reference to 25 patients who underwent surgical re-staging, indicating that the disease was understaged clinically in 24 per cent (T less than P), as well as in reference to attainment of true (pathological) complete remission and to other urothelial tract trials. While this therapy seems to have limited antitumor activity against nontransitional cell histological cancer, stage Tis disease and later development of de novo lesions, the regimen is efficacious in selected patients with advanced urothelial tract transitional cell carcinoma.

In a retrospective review the response of 67 patient with metastatic adenocarcinoma of the prostate to the administration of exogenous testosterone was analyzed. Among 52 patients in whom objective and/or subjective responses were evaluable 45 experienced unfavorable responses. There was prompt regression of most unfavorable responses with testosterone withdrawal. The duration of treatment required to evoke an unfavorable response was related to the clinical status of the patient. Twenty-five per cent of patients with symptomatic metastases who had received no prior treatment, 36 per cent in symptomatic remission after endocrine therapy and 94 per cent with symptomatic relapse after endocrine therapy experienced unfavorable responses within 30 days of treatment. No patient had objective evidence of tumor regression during testosterone therapy but 7 patients, 6 with remission and 1 untreated, experienced symptomatic benefit. We conclude that the response of patients with metastatic prostate cancer to exogenous testosterone is related to the mass and endocrine treatment status, and that exogenous testosterone can stimulate prostatic neoplasms that proliferate in the absence of normal endogenous testosterone levels.

This study of the epidemiology of cancer of the prostate was based on a retrospective investigation of 300 patients with cancer of the prostate and 400 controls, a review of the charts of an additional 350 patient with prostate cancer, and a review of the literature. The main etiologic lead to which this study could not contribute is the rarity of clinical prostatic cancer in Japan and its increase among Japanese immigrants in the U.S. However, the low rate among Jewish males in the U.S. seems to be related to a lower rate of prostatic cancer among immigrants from Eastern Europe. U.S. Negroes have a higher incidence rate than Caucasians. No significant relationship was found to socioeconomic status, marital status, fertility, social habits, previous diseases, weight, height, hair distribution, or laboratory data.

This study shows that intravesical therapy with BCG delays tumor progression and death from tumor in patients who present with superficial bladder cancer.

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