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Biomedical subjects

G R Prout

Publications and source records attributed to G R Prout.

At least 91 records · Page 5Linked to original sources

A comparison of cisplatin and the combination of cisplatin and cyclophosphamide in advanced urothelial cancer. A National Bladder Cancer Collaborative Group A Study.

A prospective multi-institutional randomized trial compared the use of cisplatin (DDP) alone to the combination of DDP and cyclophosphamide in patients with advanced urothelial cancer. Patients were stratified according to measurable or evaluable tumor and performance status. The dose of DDP was 70 mg/m2 and the initial dose of cyclophosphamide was 750 mg/m2. There were ten objective responders (20%), including five complete responders, among the 50 evaluable patients who received DDP alone, and seven responders (11.9%), three complete, among the 59 receiving the combination therapy. Approximately one third of the patients in each treatment arm were stable at the nine-week evaluation. There was no statistical significance between the response rates in the two treatment arms.

Cisplatin↗

Carcinoma in situ of the urinary bladder with and without associated vesical neoplasms.

Of 99 patients who had carcinoma-in situ (TIS) at least once between 1970 and 1980, 84 were subjected to detailed analysis and pathologic review. They may be classified into four groups: (Group 1) 14 patients, who presented with invasive bladder carcinoma (TCC) associated with TIS; (Group 2) 15 patients who, subsequent to the diagnosis of TIS with or without another superficial TCC developed muscle invasion (12 patients) or metastases without muscle invasion (three patients); (Group 3) 29 patients who underwent cystectomy for superficial TCC (Ta or T1, or TIS alone). Twenty (69%) had extravesical superficial extension. Two patients developed metastases subsequent to undergoing cystectomy; and (Group 4) 26 patients with TIS proven at least once who have not developed muscle invasion, metastases nor have undergone cystectomy. Nineteen had previous non-TIS superficial TCC. All patients in Groups 2 and 4 were treated conservatively (TUR +/- intravesical chemotherapy) when the initial diagnosis of TIS was made. Twelve patients in Group 3 underwent cystectomy within a month of the diagnosis of TIS. When 38 patients found to have TIS in association with the first diagnosis of superficial transitional cell carcinoma of the bladder were compared with 32 patients who had TIS diagnosed subsequent to their initial diagnosis of transitional cell carcinoma, the former group fared significantly worse (P less than 0.01) in regard to muscle invasion, metastases, or clinical indications for cystectomy.

Aged↗

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison.

A total of 180 patients with carcinoma of the prostate limited to the pelvis were treated with one of two external beam irradiation techniques between 1972 and 1979. One hundred and sixteen patients were treated with conventional pelvic megavoltage x-ray therapy. Sixty-four patients were treated with combined pelvic x-ray therapy plus a perineal proton beam boost to a carefully defined prostatic tumor volume. A 160 MeV proton beam has been modified to irradiate patients with localized tumors by using conventional treatment schedules. This proton beam has the physical advantage over megavoltage x-rays of reducing the dose to normal tissues adjacent to the tumor volume. By using the proton beam boost we have delivered an increased prostatic tumor dose of 500 to 700 cGy without increasing treatment morbidity at all. The two groups are actuarially analyzed for patient survival, disease-free survival and local recurrence-free survival, and thus far, no significant differences have been noted. Because of the minimal complications observed in the proton group despite a 10% increase in dose, a randomized clinical trial comparing these two treatment techniques is studied.

Clinical Trials as Topic↗

The addition of chemotherapy to hormonal therapy for treatment of patients with metastatic carcinoma of the prostate.

Patients with advanced prostate carcinoma that had been stabilized by orchiectomy (ORCH) or hormone therapy for at least 3 months, were randomized to either diethylstilbestrol (DES) alone or DES plus Cytoxan or DES plus Emcyt. A total of 188 patients were randomized between July, 1976 and February, 1982 of which 161 were evaluable for objective response to treatment. Objective response rates, response duration, or survival experiences were not demonstrably different between treatment arms, either for all patients or within good or poor prognosis groups determined by initial pain or acid phosphatase level. Subjective improvements in performance status were small for each treatment. Pain relief was somewhat greater in the chemotherapy-hormone combinations than in the DES/ORCH, but the advantage was not statistically significant. Side effects were primarily nausea and vomiting and leukopenia, mostly in the DES + Cytoxan arm. The duration of stabilization prior to entry did not influence response overall, although there were opposing trends within each of the two chemotherapy arms. The premise for combining antitumor agents with hormones before hormone failure is still felt to be a more logical approach than waiting for the ultimate hormone failure, and a combination of hormones plus two antitumor agents is being evaluated in a subsequent ongoing trial where a more rigid design limits the duration of the preentry period of hormone stabilization.

Aged↗

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.

Aged↗

Invasive bladder cancer: tumor configuration, lymphatic invasion and survival.

The pathologic slides of 86 patients who underwent radical cystectomy for invasive (stage T2 plus) bladder carcinoma were reviewed. The tumors were classified according to the demonstration or absence of small vessel invasion and the papillary or solid configuration. Of the 86 patients regional nodal metastases were noted in 24. Eighteen of 48 patients (38 per cent) with small vessel invasion also had nodal metastases compared to 6 of 38 (16 per cent) without small vessel invasion. Of the 62 patients without nodal metastases the crude 5-year survival was 52 per cent for 32 without small vessel involvement compared to 30 per cent for 30 with small vessel involvement.

Adenocarcinoma↗

A comparison of estramustine phosphate versus cis-platinum alone versus estramustine phosphate plus cis-platinum in patients with advanced hormone refractory prostate cancer who had had extensive irradiation to the pelvis or lumbosacral area.

Single and combination chemotherapy was compared in a clinical trial for men with advanced, metastatic prostate cancer who had received prior pelvic irradiation and had had progression of disease despite hormonal therapy. The 149 patients were randomized to receive estramustine phosphate or cis-platinum alone or in combination. Of the 149 patients 25 (17 per cent) were excluded from the study but 124 were evaluated for response and survival. Entry variables were distributed similarly among patients in each treatment arm. There were no complete or partial responders but there were nearly twice as many patients whose disease was stabilized (33 per cent) on the combination regimen compared to estramustine phosphate (18 per cent) and about a third more than for cis-platinum (21 per cent). Analysis of survival revealed some advantage for patients on combination therapy. Major toxicities for all treatments were nausea and vomiting (62 to 88 per cent) and accompanying anorexia (72 to 95 per cent). Azotemia developed in 45 per cent of the patients receiving combination therapy. In addition an elevation in serum creatinine occurred in 22 per cent of the patients receiving combination therapy and in 17 per cent of those receiving cis-platinum alone. Myelosuppression occurred infrequently.

Aged↗

Evaluation of prostate specific acid phosphatase and prostate specific antigen in identification of prostatic cancer.

The peroxidase-anti-peroxidase technique was used to stain for prostate specific acid phosphatase and prostate specific antigen in 12 patients with primary tumors and in 12 patients with metastases in whom the nature of the tumor was in doubt after routine histopathological studies. Nine of the primary tumors were positive for both markers and an additional 2 tumors stained for prostate specific antigen only. Six metastatic lesions stained for both markers and a seventh for prostate specific antigen alone. Thus, 11 of 12 primary tumors and 7 of 12 metastases studied were proved to be of prostatic orgin. While the peroxidase staining was sometimes weak and uneven this method, using prostate specific antigen and prostate specific acid phosphatase, allowed for ready identification of metastases. The heterogeneity of the tumors in regard to these 2 prostate markers is demonstrated, and the value of staining for prostate specific acid phosphatase and prostate specific antigen is emphasized.

Acid Phosphatase↗

Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer.

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.

Aged↗

Use of monoclonal antibodies for the localization of tissue isoantigens A and B in transitional cell carcinoma of the upper urinary tract.

Employing the indirect immunoperoxidase technique, monoclonal antisera against blood group antigens A and B were used to localize the corresponding tissue isoantigens in normal ureter and transitional cell carcinoma of the ureter and renal pelvis in 29 patients. All five cases of normal ureters showed positive staining of tissue isoantigens within the transitional epithelium, and all twelve cases of noninvasive transitional cell carcinoma showed similar staining in tumor cells. Of the remaining twelve cases who had invasive tumor, eight lacked tissue isoantigens, while four cases exhibited positive staining. These results support the earlier findings that normal urothelium and noninvasive transitional cell carcinoma of the urinary tract possess ABO tissue isoantigens, while these isoantigens are most frequently absent in invasive tumors. In addition, this study also demonstrates that invasive transitional cell carcinoma of ureters and renal pelvis may continue to possess tissue isoantigens when studied by this sensitive, specific method.

ABO Blood-Group System↗

Transitional cell carcinoma of renal pelvis.

Sixty-eight patients with transitional cell carcinoma of the renal pelvis were studied with respect to clinical presentation, tumor grade, stage and location, subsequent development of other urothelial tumors, and patient survival. Of the 66 patients with adjacent mucosa available for evaluation, 63 (95 per cent) had abnormal findings with severe dysplasia and CIS common in the high-grade, high-stage tumors. Twenty-eight patients (41 per cent) had transitional cell carcinoma previously, concomitantly, and/or subsequently, and in 14 patients (21 per cent) subsequent bladder tumors developed. Because of the relatively high tumor recurrence rate in the ureter (16 per cent) in patients who underwent subtotal ureterectomies, nephrectomy and complete ureterectomy including a bladder cuff should be the operation of choice in patients with carcinoma of the renal pelvis.

Carcinoma, Transitional Cell↗

Bladder cancer.

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Humans↗

Rat bladder isograft model for focal carcinoma.

A model for focal bladder carcinoma in rats was developed with the use of an isograft technique. Bladder tumors developed by carcinogen induction with FANFT or MNU were grafted to bladders of syngeneic rats. Ninety-six per cent (56 our of 58) of the grafts were taken and 83 per cent (34 out of 41) of the grafted tumors remained neoplastic. Most of the grafts from FANFT-induced tumor remained localized at the original site whereas many from the MNU-induced tumor spread beyond the original graft area. The model system may be useful for the evaluation of chemotherapeutic agents as well as for the studies of basic mechanisms of tumor growth and spreading.

Animals↗

Immunohistochemical identification of prostatic acid phosphatase: correlation of tumor grade with acid phosphatase distribution.

The localization and distribution of prostatic specific acid phosphatase (PSAP) in normal, hyperplastic and neoplastic prostates were studied by specific immunohistochemical of normal and hyperplastic prostates. In adenocarcinoma of the prostate, a correlation of the PSAP staining with the degree of differentiation and the ability of the tumor to form a gland was observed: more intense and uniform staining in well differentiated tumors and less intense and more variable stains in poorly differentiated tumors. The same correlation was also observed in tumors metastasized to lymph nodes and other organs.

Acid Phosphatase↗

Discouraging results for high dose external beam radiation therapy in low stage (O and A) bladder cancer.

Eight patients who received high dose external beam radiation therapy for low stage (O and A) bladder cancer with curative intent subsequently presented with recurrent tumors or complications of radiotherapy that led to cystectomy. The dismal results of high dose radiotherapy in these patients prompted us to review the published results for so-called definitive radiation therapy in patients with low stage bladder cancer. From this review and our own patients we conclude that high dose external beam radiotherapy is less than optimal treatment for patients with low stage bladder cancer. This is true even for the subset of patients with tumor characteristics that place them at high risk for the subsequent development of invasive disease.

Aged↗

Intravesical therapy of low stage bladder carcinoma with mitomycin C: comparison of results in untreated and previously treated patients.

There were 28 patients with superficial bladder carcinoma (Ta, Tl or TIS) entered into protocols for intravesical therapy with mitomycin C. Of the 28 patients 16 had failed previously on thio-tepa (group A), 7 had responded successfully to thio-tepa (group B) and 5 had never received thio-tepa (group C). There were 5 complete responses and 9 failures to mitomycin C therapy in group A. There were 5 and 4 complete responses to mitomycin C therapy in groups B and C, respectively. The treatment plan consisted of the instillation of 40 mg. mitomycin C in 40 cc water weekly for 8 weeks. Because of severe local irritative symptoms 3 of the 28 patients did not complete the course of therapy. In another patient a diffuse body rash developed after the third instillation. Mitomycin C seems effective in ablating low stage bladder carcinoma, although it is less effective in patients who have failed prior thio-tepa therapy.

Adult↗

Ta and T1 bladder cancer: location, recurrence and progression.

An analysis of 58 patients who presented with their first superficial bladder tumour(s) stage Ta or T1 and who were followed prospectively is presented. Tumour characteristics which correlated well with the likelihood of new tumour occurrence were invasion of lamina propria, multiplicity, size equal to or greater than 3 cm and abnormal selected mucosal biopsies. Positive urinary cytology and higher grade tumours correlated, though less strongly. Development of higher grade or stage in subsequent tumours (i.e. progression) was associated with initial tumour multiplicity. While initial tumours were rarely found on the dome (5.2%), new tumour occurrences involved the dome in 29% of patients.

Adult↗