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Biomedical subjects

W F Whitmore

Publications and source records attributed to W F Whitmore.

At least 127 records · Page 7Linked to original sources

Interstitial radiation: short-term palliation or curative therapy?

The management of clinically localized prostatic cancer by interstitial implantation of 125I seeds has been under exploration at Memorial Sloan-Kettering Cancer Center for thirteen years. This investigation was prompted by clinical evidence of the radioresponsiveness of some prostatic cancers, the limited applicability of surgical excision, and the possibility that interstitial therapy would have less of an adverse effect on the quality of life than would alternative treatments. Cumulative experience indicates that the technique is associated with low morbidity and mortality and high functional preservation rates; local control rates (routine biopsies were not done), within the constraints of still-limited follow-up intervals, are in the 80 per cent to 90 per cent range; and actuarial survival rates at nine years (including patients who received endocrine therapy for metastatic or intractable local disease) are approximately 90 per cent for T1, 60 per cent for T2, and 45 per cent for T3 lesions. Approximate actuarial nine-year survival rates are 80 per cent for all patients with negative nodes and 50 per cent for all patients with positive nodes. Taking into account limitations of the data and the hazards of comparing this therapy with other uncontrolled treatments, 125I appears to be a therapeutic option for the control of clinically localized prostatic cancer.

Actuarial Analysis↗

Intravesical administration of bacillus Calmette-Guérin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial.

In an attempt to prevent, delay, or reduce further tumor occurrence, 88 patients with recurrent, superficial carcinoma of the urinary bladder were randomly assigned to receive either standard therapy (cystoscopy with fulguration) or standard therapy and bacillus Calmette-Guérin (BCG). BCG was administered intravesically and percutaneously once weekly for 6 weeks. No serious toxicity was seen. There were 43 evaluable patients in each of the two groups. Results in the BCG group versus the control group were as follows: reduction in the number of recurrent tumors (43 vs 27 patients [P less than 0.001] ); conversion to negative cytology (11 of 33 vs three of 34 patients [P less than 0.05] ); and tumor progression requiring cystectomy (three vs 15 patients [P less than 0.001] ). Disease-free interval (P less than 0.001), time with negative cytology (P less than 0.001), and time to progression of disease (P less than 0.003) were longer in patients treated with BCG. These results indicate that the combination of standard therapy and BCG is more effective than standard therapy alone in patients with recurrent superficial bladder tumors.

Adult↗

Effect of intravesical Bacillus Calmette-Guérin on detection of a urothelial differentiation antigen in exfoliated cells of carcinoma in situ of the human urinary bladder.

Flow cytometry was used to detect and quantify expression of a urothelial differentiation antigen (Om5) and nuclear DNA in exfoliated epithelial cells of the urinary bladder from 15 patients with nonpapillary carcinoma in situ during and after intravesical therapy with Bacillus Calmette-Guérin (BCG). Before BCG treatment exfoliated cells reacting with the mouse monoclonal antibody Om5 were found in 13 cases. Following treatment Om5 positive cells were still present in 9 cases but 4 patients who had had Om5 positive cells prior to BCG therapy no longer had detectable antigen-positive cells after therapy. Thus intravesical BCG therapy can alter detection of a urothelial differentiation antigen in exfoliated bladder epithelial cells. It is not certain whether this antigen or other differentiation antigens measured by flow cytometry will advance our present techniques for assessing effects of therapy on carcinoma in situ and other bladder tumors. However, five of nine patients showing persistence of Om5 positive cells after therapy were found to have recurrent tumor by biopsy and two others had positive cytology (median follow-up, 13 months). None of the four without detectable antigen-positive cells after therapy had clinical evidence of tumor by cystoscopy, biopsy, or cytology (median follow-up, 12 months). It now appears feasible and desirable to initiate clinical investigations of this and other differentiation antigens in combination with DNA by flow cytometry of bladder irrigation specimens.

Antigens, Neoplasm↗

Consideration for treatment of upper urinary tract tumors with topical therapy.

The use of topical chemotherapy for the treatment of upper urinary tract urothelial tumors and the selection of patients to receive this treatment remain problematic because of the relatively infrequent occurrence of these tumors compared with similar tumors within the bladder. The lack of clinicopathologic information on upper urinary tract urothelial tumors makes pretherapy diagnosis and clinical staging difficult. In addition, there are problems associated with delivery of the agent, and there is not as yet an effective method of surveillance after treatment. Only continued investigation with endoscopic diagnosis and treatment, as well as longitudinal follow-up, will determine methods of patients selection and the optimal use of topical chemotherapy.

Administration, Topical↗

Experience with flutamide in patients with advanced prostatic cancer without prior endocrine therapy.

Seventy-two patients with advanced prostatic carcinoma without previous endocrine therapy were treated with an oral nonsteroidal antiandrogen, flutamide. Sixty-three patients (87.5%) had a favorable response, and 9 patients showed no response. Flutamide appears to be a safe antiandrogen, usually effective in the management of patients with advanced prostatic cancer who have had no prior endocrine therapy.

Acid Phosphatase↗

Estrogen, progesterone, and androgen-binding sites in renal cell carcinoma. Observations obtained in Phase II trial of flutamide.

A Phase II disease-oriented drug trial using flutamide (4'-nitro-3'trifluoro-methylisobutyranilide) 250 mg by mouth three times a day was undertaken in 28 patients with advanced, bidimensionally measurable renal cell carcinoma. Of 25 adequately treated cases, 1 (4%, 95% confidence limits 0-12%) had a partial remission lasting 9+ months, and 2 had stabilization of disease lasting 6 and 15 months, respectively. Flutamide demonstrated no significant antitumor activity in patients with disseminated renal cell carcinoma. Including patients entered in this study, 62 specimens were evaluated for steroid binding sites using a fluorescent method: 33 of 62 specimens assayed showed no hormone-binding sites, and only 12 cases had androgen binding. Of the 12 of 23 patients receiving flutamide who were biopsied and had an adequate sample for steroid-binding site determination, estrogen binding was demonstrated in 6, androgen binding in 3, and progesterone binding in 4. Since this study did not obtain a sufficient number of cases with androgen-binding positivity, the possible efficacy of flutamide in such cases cannot be excluded.

Adenocarcinoma↗

The VAB-6 regimen in the treatment of metastatic seminoma.

In an attempt to improve complete remission rates, seven patients with Stage III or bulky Stage II pure seminoma of the testis were treated with the VAB-6 regimen. Cyclophosphamide 600 mg/m2 of body surface, vinblastine 4 mg/m2, dactinomycin 1 mg/m2, and bleomycin 30 mg were given by intravenous (IV) push on the first day. This was immediately followed by 3 days of continuous bleomycin infusion (20 mg/m2/day X 3) and cisplatin 120 mg/m2 IV over 20 to 30 minutes on the fourth day. Induction was repeated three more times. All patients achieved complete remission with chemotherapy alone. Five patients remain in CR 38, 36, 30, 29, and 19 months, respectively, and two relapsed 9 and 18 months, respectively, from beginning of chemotherapy. One patient required broad spectrum antibiotics for fever during severe myelosuppression. One patient developed temporary elevation of serum creatinine to 4 mg/dl after the second treatment with platinum, and was given reduced platinum doses with subsequent inductions. The VAB-6 regimen is effective in the treatment of advanced metastatic seminoma.

Abdominal Neoplasms↗

Relationship of pretreatment transurethral resection of the prostate to survival without distant metastases in patients treated with 125I-implantation for localized prostatic cancer.

The authors assessed the relationship between transurethral resection of the prostate (TURP) and the probability of survival without distant metastases (survival) in patients with clinically localized prostatic cancer. Fifty-eight patients with obstructive voiding symptoms who underwent TURP within 12 months before pelvic lymphadenectomy and 125I-implantation were compared with 131 patients who did not require TURP before implantation. None received other treatment for the tumor. The overall survivals for the two groups were not significantly different, P greater than 0.1. When stratified by tumor grade or the presence or absence of pelvic lymph node metastases, the survivals for the two groups were also similar, P = greater than 0.1. However, survival associated with Stage C tumors was greater in the No TURP than in the TURP group (P = 0.003), and survival associated with Stage C tumors was greater in the TURP than in the No TURP group (P = 0.005). These data fail to provide convincing evidence that transurethral resection of prostatic cancers has an unfavorable impact on disease progression.

Adenocarcinoma↗

Poorly differentiated (anaplastic) seminoma of the testis.

Anaplastic seminoma constitutes approximately 17% of total experience with seminoma at Memorial Sloan-Kettering Cancer Center. Among 25 previously untreated patients, 11 (44%) were clinical Stage I, and 14 (56%) were clinical Stage II or III. Treatment of these 25 patients with the same regimens employed for classical seminoma yielded an overall 80% 5-year apparent cure rate. Survival rates were poor in eight previously treated patients referred with recurrence.

Adult↗

Potentiation of methylglyoxal-bis-guanylhydrazone by alpha-difluoromethylornithine in rat prostate cancer.

The polyamines, putrescine, spermidine, and spermine, are fundamentally related to both normal and neoplastic cell proliferation. The prostate gland and prostatic tumors in man and rodents contain large amounts of polyamines. This suggests that inhibition of polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosyl-methionine decarboxylase (SAMDC) may retard the growth of prostatic cancer. Since alpha-difluoromethylornithine (DFMO) and methylglyoxal-bis-guanylhydrazone (MGBG) are irreversible and competitive inhibitors of ODC and SAMDC, respectively, they were tested as single agents and in combination on a transplantable rapidly growing and hormone-resistant G subline of the Dunning R-3327 rat prostatic adenocarcinoma. Groups of rats bearing tumors were treated with various regimens of DFMO, MGBG, and DFMO plus MGBG, daily for 21 days. Analysis of differences in tumor growth between treatment groups and controls showed DFMO had no antitumor effect but was well tolerated, MGBG retarded growth rate significantly but resulted in drug deaths in over 50% of the animals, and the combination of DFMO and MGBG resulted in rapid decline in tumor growth rates after 5 to 9 days of treatment with reduced toxicity. At 21 days, or death, 38 of 60 (63%) rats had no viable tumor on histologic study, whereas tumor was present in each of the animals in the other groups. Alpha-difluoromethylornithine increased the intracellular uptake of MGBG and potentiated the antigrowth activity of MGBG on a hormone refractory rat prostatic tumor with less toxicity than MGBG alone.

Adenocarcinoma↗

Correlation of serum tumor markers in advanced germ cell tumors with responses to chemotherapy and surgery.

Remission rates induced by chemotherapy alone or by combined chemotherapy and surgery were analyzed in relation to specific serum tumor marker abnormalities immediately before treatment in 103 patients with Stage III or bulky Stage II nonseminomatous germ cell tumors. Complete remission occurred in 92% (12 of 13) of patients with normal levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), in 26% (6/23) with elevated AFP only, in 46% (13/28) with elevated HCG only, and in 39% (13/36) with abnormalities of both AFP and HCG. Patients with elevated AFP less frequently had a complete remission (CR) to chemotherapy (CR, 34% versus 61% with normal AFP), but benefitted from adjunct surgery (CR, up to 59%). Patients with very high (greater than 1000 ng/ml) serum AFP or HCG responded poorly to chemotherapy (CR, 17%) but especially large tumor burdens may have contributed to these unfavorable responses. Patients with both minimal and advanced metastatic disease had higher CR rates if they had serum tumor marker levels below rather than above 1000 ng/ml. Adjunct surgery eliminated the correlation between the "poor prognostic factors" associated with specific marker abnormality and an incomplete response to chemotherapy by rendering a significant number of such patients free of disease through resection of residual metastatic deposits.

Antineoplastic Combined Chemotherapy Protocols↗

Sarcomas of the kidney.

We report a retrospective study of 18 patients with renal sarcomas seen between 1950 and 1980. Renal sarcomas are highly malignant neoplasms and the over-all prognosis is poor, with only 2 long-term survivors in this series. Radical nephrectomy seems to be the treatment of choice.

Adult↗

Flow cytometric evaluation of sperm from patients with testicular carcinoma.

Semen samples from 14 patients with testicular cancer were analyzed by new flow cytometry techniques and by conventional semen analysis. Samples were obtained post-unilateral orchiectomy and prior to further treatment. With only 1 exception, light microscopic analysis of sperm count and morphology indicated a decrease of normal sperm production and incomplete or abnormal differentiation. Flow cytometry of semen aliquots showed, with the same exception as above, increased acridine orange staining of the sperm nuclear chromatin, attributed to abnormal chromatin composition and condensation. In addition, the chromatin structure of isolated sperm nuclei was abnormally sensitive to thermal stress. These changes were present up to 15 months post orchiectomy and suggest abnormal spermiogenesis in the contralateral testis of patients with testicular tumors. Of the 14 patients studied only 1 fell well within the normal range for all parameters measured; 2 other patients were in the low normal range for all parameters and 1 patient fell below normal for light microscope derived measurements but was normal by flow cytometry. The other 10 patients had abnormal measurements for all parameters. The assessment of spermiogenesis by flow cytometry studies of sperm chromatin appears to be a sensitive and valuable new parameter of fertility that cannot be determined by conventional semen analysis.

Acridine Orange↗

Inguinal lymph node metastases from germ cell testicular tumors.

Between 1948 and 1982, 22 patients were seen with metastasis to the inguinal nodes from testicular germ cell tumors: 8 had a history of unilateral or bilateral orchiopexy with or without herniorrhaphy, 4 had nonsurgically corrected or uncorrected cryptorchidism, 9 had a history of herniorrhaphy, hydrocelectomy or transscrotal orchiectomy and 1 had no history of scrotal, iliac or inguinal surgery, or of tunica vaginalis or scrotal wall involvement by tumor. The histological type was pure seminoma in 5 patients, embryonal carcinoma in 7 and mixed tumor in 10. Treatment was individualized for tumor type and mode of presentation, and varied during the years according to the modalities available. At the time of this report 8 of 22 patients (36 per cent) are alive without evidence of disease from 2 to 29.5 years, 3 (16 per cent) have died without evidence of disease 10 to 17 years after treatment, 10 (45 per cent) have died of metastases 10 months to 6 years after treatment and 1 has been lost to followup. The over-all incidence of groin metastases from testicular carcinoma is low, even with a history of scrotal or inguinal surgery.

Adolescent↗