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Biomedical subjects

N H Slack

Publications and source records attributed to N H Slack.

At least 19 recordsLinked to original sources

Effect of axillary nodal status on the long-term survival following mastectomy for breast carcinoma: nodal metastases may not always suggest systemic disease.

Records of 215 patients receiving radical mastectomies from 1958 to 1968 at Roswell Park Memorial Institute were reviewed for the significance of axillary nodal status on long-term survival and recurrence. Ten-year disease-free interval rates were 83%, 47%, and 17%, respectively, for patients with negative nodes, 1-3 positive nodes, and greater than or equal to 4 positive nodes. Fifteen-year rates were 80%, 37%, and 8%, respectively. Survival and disease-free interval curves for the 3 nodal status groups were significantly different from each other (P less than 0.0001). Curves for three subclasses of the greater than or equal to 4 positive node group (4-6, 7-12, and greater than or equal to 13) were similar in overall survival, but were significantly (P = 0.04) different for disease-free interval, due to a rapid rate of recurrence in the greater than or equal to 13 positive node group. Hazard rates of treatment failure during each successive 3-year period for 9 years following mastectomy for those with 1-3 positive nodes or greater than or equal to 4 positive nodes decreased with time, whereas the rates for those with negative nodes were low and relatively constant throughout follow-up. These findings support the thesis that a significant proportion of negative nodes patients are cured by mastectomy and that a smaller group of node-positive patients have regional disease with a chance of cure by mastectomy.

Axilla↗

Prostatic cancer. Treated at a categorical center, 1980-1983.

This report covers the experience from 537 patients with prostatic cancer seen at Roswell Park Memorial Institute (RPMI) from 1980 through 1983. This is a look at experiences in the early 1980s and is a continuation of the series covering the decades of the 1950s, 1960s, and 1970s. Referrals continue to dominate the series (85% of cases) but are now only slightly younger (65 years) than in-house diagnoses (66 years), of which one third were diagnosed at autopsy. Survival rates in this series, although limited in follow-up, were similar at two years to those in the 1970s and in the extensive series collected by the survey of the American College of Surgeons. Multiple primary tumors were observed in 22 per cent of this series, most frequently involving the bladder in addition to the prostate. Treatments continue to involve chemotherapy earlier in the course of disease as part of a succession of therapeutic modalities that include transurethral resection of prostate (TURP) or prostatectomy, lymph node dissection, external irradiation, castration, and hormones.

Age Factors↗

Prognostic importance of prostate-specific antigen for monitoring patients with stages B2 to D1 prostate cancer.

To evaluate the prognostic value of prostate-specific antigen (PA) for detection of tumor growth after definitive therapy, 602 sera from 70 patients with stages B2 to D1 prostate cancer (26 of whom recurred) were analyzed in a blind study. Using Cox's proportional-hazards model, a highly significant association was found between serially measured PA and disease-free survival time (p = 0.0002). A positive predictive value of 100% was found for some markedly elevated PA levels and confirmed recurrence of disease. In fact, this study suggested that once a PA level of 88 ng/ml was reached, there was an average time of less than 2 months before a recurrence was clinically confirmed. Tumor growth in patients who recurred was indicated by a PA elevation before recurrence in 92% (24 of 26) as opposed to 20% (9 of 44) in disease-free patients. Additionally, in these 24 of 26 patients, levels of PA were elevated 12 months (mean lead time) before a confirmed disease recurrence. In patients who were still disease free, serial PA appeared to increase concurrently with putative tumor growth as shown by the initial surgical stage. Generally, the greater the PA level the more advanced was the stage of disease (B2 to D1). These data suggest that PA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined prostate cancer.

Antigens, Neoplasm↗

A reexamination of the stable category for evaluating response in patients with advanced prostate cancer.

Stable response to therapy in patients with advanced prostate cancer, as experienced in clinical trials of the National Prostatic Cancer Project (NPCP) has been re-examined. Data from 10 completed trials, totaling over 1300 patients, have been examined for survival patterns within categories of response to therapy. Survival patterns, for patients alive at 12 weeks, were significantly poorer for patients who were categorized as progressors after 12 weeks on treatment than for those who were categorized as stable or as partial regressions. Furthermore, comparisons of survival patterns for those patients who were categorized as stable or partial regression revealed no statistically significant differences between them. The concerns over the use of stable as an indicator of response and the problems in establishing its true meaning are discussed. All things considered, the use of stable is a valid means to evaluate the status of patients in clinical trials of treatment modalities for advanced cancer of the prostate.

Adult↗

Stable versus partial response in advanced prostate cancer.

Stable response to therapy in patients with advanced prostate cancer, as experienced in clinical trials of the National Prostatic Cancer Project (NPCP), has been reexamined. Data from ten complete trials totaling over 1,300 patients have been examined for survival patterns within categories of response to therapy. Survival patterns, both for all patients and for those alive at 12 weeks, were significantly poorer for patients categorized as progressors after 12 weeks on treatment than for those categorized as stable or as partial regressions. Furthermore, comparisons of survival patterns for those patients categorized as stable or partial regression revealed no statistically significant differences between them. The similarity of survival for the stable and partial regression categories indicates that the stable category represents more than a segment of the population with slowly progressing disease and can be taken as an indicator of response to therapy.

Adult↗

Criteria for evaluating patient responses to treatment modalities for prostatic cancer.

Criteria for evaluating response to therapy for both early and late stages of prostate cancer, as developed by the National Prostatic Cancer Project, are presented and discussed. Detection of bone metastases and monitoring of changes in existing bone lesions are critical to these criteria for early and late disease, respectively. The prognosis, or survival experience, of groups of patients for each response category is also discussed.

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↗

A decade of experience with chemotherapy for prostate cancer.

Chemotherapy for prostate cancer has been demonstrated by the Clinical Trials Program of the NPCP and by other cooperative and individual studies both as single antitumor agents and combinations of agents to provide additional benefit to patients with advanced disease that no longer respond to hormonal therapy, markedly more so than could be provided by a host of palliative and real or synthetic hormonal agents commonly used in this type of patient. There is also some evidence to support the premise that adding antitumor agents to hormones as initial treatment for metastatic disease is more effective than waiting for the ultimate hormone failure, at least in patients with poorer prognosis.

Antineoplastic Agents↗

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↗

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↗

Observations of prolonged use of oral Emcyt in prostatic cancer patients.

Experiences resulting from Emcyt therapy in patients with both newly diagnosed and hormone refractory advanced prostate cancer, as well as on adjuvant to surgery or radiotherapy in earlier disease are presented. Data from trials of the National Prostatic Cancer Project (NPCP) and a series from Roswell Park Memorial Institute (RPMI) were divided into short-term (up to twenty weeks and up to fifty-two weeks in adjuvant trials) and long-term therapy. Baseline disease and patient characteristics and toxicities encountered in these two treatment-duration groups were compared. Patients in a more favorable health or disease status and/or responded to therapy were more frequently in the long-term group. Patients in the long-term group tended to have higher over-all incidences of toxicity; and although many had occurrences begin as early as those in the short-term group, they were able to tolerate the therapy for relatively long periods. The agent is thus both effective and can be given safety for long periods of time.

Acid Phosphatase↗

Placenta-like isoenzyme of alkaline phosphatase in prostatic cancer.

Assays for serum placenta-like (Regan) isoenzyme of alkaline phosphatase were done on 157 samples from 96 patients with prostatic cancer entered into various National Prostatic Cancer Project protocols. Elevated placenta-like isoenzyme levels were found in 19 patients (20 per cent). Increased isoenzyme activity was seen in some patients with early clinical stages of the disease (B1 and B2), as well as in those with advanced disease. As in other reports results were not consistent in any individual patient. No correlations could be made between elevated isoenzyme activity and either stage of the disease or response to therapy. The placenta-like isoenzyme of alkaline phosphatase appears to be a nonspecific oncodevelopmental marker that is not helpful alone as a diagnostic indicator but that may be promising as part of a profile of markers for a patient with prostatic cancer.

Alkaline Phosphatase↗

Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

Acid Phosphatase↗