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Biomedical subjects

N H Slack

Publications and source records attributed to N H Slack.

6 recordsLinked to original sources

Relationship of prior hormonal therapy to subsequent estramustine phosphate treatment in advanced prostatic cancer.

The relationship of prior hormonal therapy to subsequent response on estramustine phosphate (Estracyt) was examined in 107 patients with advanced prostatic cancer treated in two different Phase II chemotherapy trials. In both trials patients with the longest prior hormonal treatment were the least likely to respond to estramustine phosphate. Patients in the series from the National Prostatic Cancer Project with a response classification to prior hormonal therapy had only a 26 per cent response to subsequent estramustine phosphate therapy, whereas 40 per cent of those with no prior response to hormonal therapy responded to estramustine phosphate. This latter group had the shortest average disease duration from diagnosis. The sample of prostate cancers studied appeared to include groups that were sensitive to both hormones and cytotoxic activity as well as to either of these two alone. These data support the contention that estramustine phosphate may act both as an estrogenic and a cytotoxic agent.

Aged

Comparison of procarbazine, imidazole-carboxamide and cyclophosphamide in relapsing patients with advanced carcinoma of the prostate.

In this third cooperative chemotherapy trial of the National Prostatic Cancer Project 165 patients with histologically confirmed, relapsing clinical stage D prostatic cancer were randomized to receive either imidazole-carboxamide, procarbazine or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on initial therapy were crossed over or randomized to receive an alternate drug. There were 129 patients available for comparison of treatments. The objective response rates (partial regression plus stable disease) were 26% for cyclophosphamide, 27% for imidazole-carboxamide and 14% for procarbazine. Subjective responses were noted in pain relief, improvement in performance status and weight gain. Procarbazine was associated with excessive toxicity, resulting in many patients (28%) discontinuing therapy within the first 3 weeks and closure of this particular arm of the study. The regimen of initial imidazole-carboxamide therapy with a later cross-over to cyclophosphamide when the disease continues to progress is associated with the longest increase in survival. Imidazole-carboxamide and cyclophosphamide appear to be active agents in advanced prostatic cancer and are worthy of continued use in this disease.

Aged

Endometrial cancer: therapeutic decision and the staging process in "early" disease.

An all inclusive, widely accepted system for correlation of indices of pathophysiology in endometrial cancer with a spectrum of therapeutic management has yet to be developed. Improved understanding of tumor growth should lead to more logical, individualized treatment especially in terms of irradiation. To support these philosophies a brief review of past reports and studies, especially the Endometrial Adjuvant Study is provided. From an analysis of 574 patients in this study, it is apparent that prognostic factors could be separated as major, differentiation, and tumor penetration and minor, number of capsules of radium and depth of uterus. A pilot study under the Gynecologic Oncology Group suggests the correlation of the major factors with lymph node involvement. Since depth of penetration and lymph node involvement are most accurately determined by surgery and pathology, surgical staging is suggested as a guide for therapeutic decision.

Clinical Trials as Topic

Five-year follow-up results of a collaborative study of therapies for carcinoma of the bladder.

Results after 5 years of follow-up in a cooperative trial of therapies for operable bladder cancer confirmed preliminary indications of a beneficial effect of preoperative irradiation. Improved survival was experienced by the one-third of the irradiated patients who experienced complete eradication of the tumor as indicated from the resected specimen 30-60 days after a 30-day course of 4,500 rads. These patients had a 55% chance of surviving 5 years as opposed to a 32% chance for those where irradiation did not eradicate the tumor, or similarly for those not irradiated. A postoperative course of chemotherapy with 5-fluorouracial appeared to act detrimentally when given to patients irradiated preoperatively, but may have had a slight benefit when given after surgery alone.

Clinical Trials as Topic

The influence of site of metastasis on tumour growth and response to chemotherapy.

Drug screening trials and general treatment of solid tumours in advanced cancer patients have been concerned only with the site of primary origin, regardless of where metastases might have seeded. Since the environment for tumour growth can differ appreciably at various anatomical sites, an investigation was undertaken to determine the effect of metastatic site on response to chemotherapy. Data from 1961 to 1965 of the screening trials of the Eastern Clinical Drug Evaluation Program were utilized. Response and location data extensive enough for analysis represented 6 sites of primary origin and 6 metastatic site groups, totalling 1687 lesions. Analysis of percentage reduction in tumour size after chemotherapy regimens of up to 60 days revealed a significant amount of variation associated with metastatic sites and a non-significant amount associated with sites of primary origin. Advanced primary tumours showed marked variation in responsiveness and some showed a difference in response to different drug groups. Generally, metastases responded better than the advanced primaries from which they were derived, except for those from breast tumours.

Antineoplastic Agents