Zew Wajsman

Combination radical surgery and multiple sequential chemotherapy for the treatment of advanced carcinoma of the testis (stage III).

Nineteen patients with advanced testicular carcinomas (Stage III) were treated by a combination of multisequential chemotherapy with vinblastine, bleomycin, platinum, adriamycin, cytoxan, actinomycin D, and reductive surgery. Of the sixteen patients who were operated on 10 patients are alive and free of disease from 5 to 15 months. Two patients are alive with residual disease and four patients died. (Three were free of malignant tumor and one had residual malignant disease.) Three patients are still receiving preoperative chemotherapy. Pathology reported benign tumors in 8 out of 16 patients operated on. All these patients were previously treated with multiple chemotherapy. Several facts emerge from this study: (1) the great effectiveness of the combination of multisequential chemotherapy and reductive surgery to produce complete clinical remission in advanced testicular carcinomas (63.6%, 13 out of 19 patients); (2) the possibility of benign transformation of these tumors (50%, 8 out of 16); (3) the importance of the second‐look surgery in testicular tumors.

Long-term Fate of 90 Patients with Superficial Bladder Cancer Randomly Assigned to Receive or not to Receive Thiotepa

We assigned randomly 90 patients treated previously for superficial transitional cell carcinoma to conventional followup or prophylactic treatment. This followup study details the late incidence of recurrence (29 of 45 patients in the prophylactic group and 34 of 45 controls), the progression of tumor grade and stage, the deaths and causes (24 patients), and the influence of initial stage, grade, carcinoma in situ and positive cytology on the outcome of treatment.

Cisplatin and Full Dose Irradiation for Patients with Invasive Bladder Carcinoma: A Preliminary Report of Tolerance and Local Response

Twenty-seven patients with invasive bladder carcinoma (clinical stages T2 to T4) who were not candidates for cystectomy were treated by transurethral resection, cis-diamminedichloroplatinum (cisplatin) and full dose radiotherapy according to protocol 8 of the National Bladder Cancer Collaborative Group A. Nausea and vomiting occurred in 74 per cent of the patients but were mild in 41 per cent. Maximum followup was 27 months and during that time 3 significant toxic reactions occurred: renal failure, systemic sepsis and a transient partial small bowel obstruction. Of 17 evaluable patients complete responses of the primary bladder cancer to the treatment were achieved in 11 of 13 with stages cT2 and cT3 cancer and in 2 of 4 with stage cT4 disease. The members of National Bladder Cancer Collaborative Group A have found transurethral resection, cisplatin and full dose external beam radiotherapy practical clinically. Longer followup will be necessary to determine if the observed high initial complete response rate of the tumor indicates real lasting benefit for these patients.

Evaluation of Biological Markers in Bladder Cancer

The value of biological markers of bladder cancer was studied in 66 patients. The markers included serum and urine carcinoembryonic antigens, serum and urine fibrinogen degradation products, total lymphocyte counts, urine lymphocytes and urine cytology. A high degree of accuracy (90 per cent) was found in correlating cytology and urinary fibrinogen degradation products with the activity of the disease. Serum and urine carcinoembryonic antigens, serum fibrinogen degradation products, total lymphocyte counts and urine lymphocytes were found to have no value in screening bladder cancer patients. Urinary fibrinogen degradation products and cytology in combination are recommended for screening and followup of patients at high risk.

Chemotherapy of Advanced Carcinoma of the Prostate with 5-Fluorouracil, Cyclophosphamide and Adriamycin

There were 33 patients with clinically relapsing advanced prostatic carcinoma (stages C and D) treated by 2 different combinations of chemotherapy. The 13 patients in group 1 received 5-fluorouracil and cyclophosphamide and 20 patients in group 2 received adriamycin and cyclophosphamide. The over-all response was 69.3 per cent in group 1 and 65 per cent in group 2. Our preliminary results should encourage further evaluation of these drug combinations by other investigators under carefully controlled conditions.

Chemotherapy of Bladder Carcinoma with Cyclophosphamide and Adriamycin

We assigned 49 patients with transitional cell carcinoma of the bladder to 1 of 3 groups: 21 patients (group 1) received cyclophosphamide alone, 10 patients (group 2) received adriamycin alone and 18 patients (group 3) received cyclophosphamide and adriamycin. The objective responses were 52.3 per cent in group 1, 10 per cent in group 2 and 50 per cent in group 3. These results suggest a significant activity of the drugs (especially in groups 1 and 3) tested in bladder cancer.

Evaluation of Lymphangiography for Clinical Staging of Bladder Tumors

Preoperative lymphangiography was done on 18 patients with bladder cancer and the results were correlated with the surgicopathological findings at the time of radical cystectomy and pelvic lymph node dissection. Correlation between radiological and pathological findings showed no falsely negative results. One patient had a falsely positive interpretation of lymphangiography. The accuracy of the study was 94 per cent. Accurate interpretation of lymphography is related to the experience of the reader. Routine use of lymphangiography in clinical staging of bladder cancer is recommended.

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Clinical Significance of Serum Alkaline Phosphatase Isoenzyme Levels in Advanced Prostatic Carcinoma

The alkaline phosphatase isoenzymes in 105 patients with stage D carcinoma of the prostate who entered the National Prostatic Cancer Study were analyzed and these values were correlated to clinical response. Only patients with at least 3 measurements of alkaline phosphatase were evaluated. In 91% of patients with metastatic bone disease, bone alkaline phosphatase was elevated. Those patients with higher pre-treatment levels of alkaline phosphatase generally showed a poorer response to therapy. The results of alkaline phosphatase isoenzyme estimation indicate that these biological markers may be used in the evaluation of patients with metastatic prostatic cancer to predict and monitor their response to chemotherapy. The evaluation of bone and liver alkaline phosphatase isoenzymes in earlier stages also may be valuable.

Steroid hormone receptors in the prostate.

Specific receptors for dihydrotestosterone and estradiol-17-beta have been identified in cytosols of the human and baboon prostate. Binding of radioactive estradiol-17-beta to the 0.4 M potassium chloride extractable component of human prostate nuclei also was demonstrated. Cyproterone acetate and diethylstilbestrol, agents of known high affinity for dihydrotestosterone and estradiol-17-beta receptors, respectively, did not bind significantly to sex hormone binding globulin and, therefore, were useful as competitors in distinguishing binding of dihydrotestosterone and estradiol-17-beta to sex hormone binding globulin and to their specific receptors. Displacement of [3H]-estradiol-17-beta binding by diethylstilbestrol in cytosols of 11 needle biopsy specimens (mean equals 16.8 mg.) from prostatic cancer patients was analyzed. These preliminary data indicated a trend towards greater competition by diethylstilbestrol for high affinity binding sites in differentiated tumor specimens from men who were not receiving estrogen therapy. Objective and subjective responses to hormone therapy were recorded in these patients, whereas the disease in those men with low displacement assay values progressed.