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Biomedical subjects

N H Slack

Publications and source records attributed to N H Slack.

At least 37 records · Page 2Linked to original sources

Multiple marker evaluation in human prostate cancer with the use of tissue-specific antigens.

Serum prostate-specific antigen and prostatic acid phosphatase were simultaneously evaluated in 22 healthy males, 29 patients with benign prostatic hypertrophy, and 192 patients with prostate cancers at various stages as well as in 30 patients with cancers other than prostate cancer. Both markers were quantitated by specific sandwich-type, enzyme-linked, immunosorbent assays with the use of specific antiserum reagents. Serum assays revealed a discordance between these two markers; thus expressions of these two biochemically and immunologically distinct prostate-specific proteins may reflect different aspects in the biology of prostate cancer. A combination test with the use of 7.5 ng of prostate antigen and 15.5 ng of prostatic acid phosphatase/ml of serum, respectively, as cutoff values resulted in a positive detection rate of 58% for prostate cancers of stages A (7/12) and B (21/36) each, 68% for prostate cancer of stage C (19/28), 92% for prostate cancer of stage D (106/116), and only 10% for benign prostatic hypertrophy (3/29). None of 52 other cancers or healthy controls was registered as positive. This study demonstrates that a multiple marker test of tissue-specific antigens can be of an additive value in the immunodiagnosis of cancer and may be a logical and effective approach at this time, in light of the unavailability of human tumor-specific markers.

Acid Phosphatase↗

Carcinoplacental isoenzyme (Regan) in carcinoma of the prostate. National Prostatic Cancer Project.

Serum samples were examined for the placental-like "Regan" isoenzyme of alkaline phosphatase in two groups of patients with advanced cancer of the prostate from clinical trials of the National Prostatic Cancer Project. In the first group, 98 samples from 76 patients over three consecutive months revealed elevated isoenzyme activity in 14 (18%) of the patients, a frequency similar to those reported for some other tumor types. Four of these patients whose serum demonstrated the "Regan" isoenzyme had samples taken more than once, and their sera had negative readings when taken a month or more before or after the sample that was positive for the isoenzyme. Comparisons of general disease and patient characteristics for patients whose sera were positive or negative for Regan isoenzyme revealed no demonstrable relationships. The second group consists of 72 samples received from 52 study patients with metastatic lesions under treatment from August 1, 1979 to November 16, 1979. Fifteen patients had sufficient serial values. In this study to date, the relationship with clinical response to treatment is inconclusive, although elevated levels of the isoenzyme appear to occur in patients with metastatic disease with bony lesions that are clinically in progression, as well as in those apparently responding to chemotherapy.

Aged↗

The use of serum isoenzymes of alkaline and acid phosphatase as possible quantitative markers of tumor load in prostate cancer.

The tumor burden of 98 patients with metastatic prostatic cancer was compared longitudinally with the activities of bone (BAP) and liver isoenzymes (LAP) of alkaline phosphatase, total acid phosphatase (AcP), and prostate-specific acid phosphatase (PAP). A quantitative association between these enzyme markers and the tumor mass was suggested by comparing the enzymes with 1) both the treatment response and the estimation of metastasis by radionuclide bone scanning; 2) metastasis based upon radiographic evidence. In addition, an apparent extensive pretreatment bone tumor load was predictive for an elevated BAP activity, which was also a suggestive poor prognosis as previously reported. An elevation of PAP, in contrast to AcP, may precede the clinical disease progression in some patients. Data presented in this report have indicated that the levels of these enzymes compared well with the extent of tumor involvement and therefore may be considered suitable as adjuvant and even quantitative biochemical markers of bone and liver metastasis.

Acid Phosphatase↗

Chemotherapy in metastatic, hormone refractory prostatic cancer using chlorambucil in combination with prednisolone versus conjugate, prednimustine (Leo 1031).

Chlorambucil plus prednisolone were administered to 11 patients with metastasis hormone refractory prostatic cancer, and the results were contrasted with a previously reported series of 23 similar patients treated with the chemical conjugate of these two agents, known as prednimustine or Leo 1031. The conjugated form of treatment (Leo 1031) had a limited therapeutic advantage, in that 3 patients experienced shrinkage of an enlarged prostate, 2 of whom also had elevated acid phosphatase levels return to normal and 5 others experienced only subjective improvement. There were, however, more adverse side effects in this group than those noted in patients treated with the combination of agents. Patients treated with the combination of drugs experienced no appreciable tumor shrinkage and none had acid phosphatase return to normal, although some reduction was noted in 8 of 11 patients who had elevated levels initially. Two of the 11 patients were considered stable for twelve months and one other remained ambulatory with mild pain for six months. Thus, to the degree that these studies permit, it is judged that the conjugated agent may have some limited therapeutic advantage not observed when the unconjugated agents were used.

Aged↗

Comparison of estramustine phosphate and vincristine alone or in combination for patients with advanced, hormone refractory, previously irradiated carcinoma of the prostate.

There were 121 men with hormonally refractory metastatic cancer of the prostate who were randomized to receive estramustine phosphate or vincristine, or the combination of these 2 agents. All patients had received prior radiation therapy (greater than 2,000 rad). There were 90 patients who could be compared for response. The objective response rates (partial regression or stabilization of disease) for the 3 treatment groups were 26 per cent for estramustine phosphate, 24 per cent for estramustine phosphate plus vincristine and 15 per cent for vincristine. Subjective parameters varied little among the 3 regimens. The median duration of response for those responding to estramustine phosphate was similar (20 weeks) to that for vincristine (22 weeks) and greater than that for the combination (13 weeks). The probability of survival did not differ significantly for patients randomized to each of the 3 regimens. The addition of vincristine to estramustine phosphate did not enhance the response rate achieved by estramustine phosphate alone and vincristine alone produced the lowest response rate. Estramustine phosphate continues to be the most active agent in previously irradiated patients with hormonally refractory metastatic cancer of the prostate.

Drug Therapy, Combination↗

A comparison of hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea and cyclophosphamide in patients with advanced carcinoma of the prostate.

This is the fifth completed randomized clinical trial of the National Prostatic Cancer Project. There were 125 patients with histologically confirmed relapsing clinical stage D prostatic cancer randomized to receive hydroxyurea, methyl-chloroethyl-cyclohexy-nitrosourea or cyclophosphamide. All patients had received and failed previous hormonal therapy. Patients whose disease progressed after 12 weeks on the initial therapy were crossed over or randomized to receive an alternate drug. There were 98 patients available for comparison of treatments. Objective responses included patients with complete or partial regression as well as stable disease. The response rates were 35 per cent for cyclophosphamide, 30 per cent for methyl-chloroethyl-cyclohexy-nitrosourea and 15 per cent for hydroxyurea. Subjective response parameters included improvement in performance status and relief of pain. Pain was improved in a fifth of the patients on each treatment area. Methyl-chloroethyl-cyclohexy-nitrosourea and hydroxyurea showed activity in advanced prostatic cancer patients but at the expense of excessive toxicity. Cyclophosphamide continues to be the most active single agent in this type of patient, particularly with regard to duration of response and survival. There was a statistically demonstrable advantage for cyclophosphamide over hydroxyurea and a marginal advantage over methyl-chloroethyl-cyclohexy-nitrosourea in survival experience.

Acid Phosphatase↗

Use of human prostate-specific antigen in monitoring prostate cancer.

The newly reported human prostate-specific antigen (PA) is a specific histiotypic product of human prostate. With the use of a sensitive enzyme immunoassay, the circulating PA in prostatic cancer patients has been evaluated clinically. In 96 patients with advanced stage of disease (D2) and receiving chemotherapies, the pretreatment serum PA levels were found to be of prognostic value with regard to the patient survival. Ten patients with metastatic prostate cancer were monitored for more than 32 weeks by 183 serial PA values and were found generally to respond to the treatment. Additionally, in another group of 32 patients who underwent curative therapies for localized prostate cancer, 161 serum samples were evaluated during periods of 12 to 114 weeks (average 56 weeks). Of these patients, five developed metastases during follow-up, and all were shown to exhibit increasingly elevated PA values, either corresponding to or preceding the clinical diagnosis of disease recurrence. These results suggest that PA is a new marker with potential value to merit further clinical study.

Antigens, Neoplasm↗

The importance of the stable category for chemotherapy treated patients with advanced and relapsing prostate cancer.

Categories of objective response to chemotherapy for 460 advanced relapsing prostate cancer patients evaluated in the initial first four randomized clinical trials of the National Prostatic Cancer Project were compared by survival and other patient and disease characteristics. The response criteria for stable were shown to delineate patients with markedly improved survival and other disease conditions relative to those designated as progression. Survival was similar for stable and partial regression patients despite more frequent reduction of primary tumor and subjective improvement in performance status, pain, and body weight in the partial regression patients. Consequently, we feel that in these studies the stable category is valid and useful for determining efficacy of treatment in patients with advancing prostate cancer.

Acid Phosphatase↗

An assessment of bone scans for monitoring osseous metastases in patients being treated for prostate carcinoma.

The National Prostatic Cancer Project held a workshop in March 1980 to examine procedures used to evaluate bone metastases. Variations in techniques used by each of 9 treatment centers, as well as the National Cancer Institute, were compared. One center in particular had developed procedures for quantitating bone scans in addition to the customary qualitative evaluation. Changes in bone scan assessments were also related to changing levels of isoenzymes of acid and alkaline phosphatase. Most consistently correlated with disease changes were prostatic acid phosphatase, as determined by counter-immunoelectrophoresis, and the isoenzyme of bone alkaline phosphatase. Gamma cameras were recommended over rectilnear scanners as were multiple spot films to concentrate on problem areas. Bone scans must be performed prior to therapy and for best assessment no sooner than 3 months to avoid the flair phenomenon. Consistency of both machine settings and patient position are paramount, as are quality of equipment and review of past scans and X-ray films where appropriate to obtain the best assessment of disease status.

Bone Neoplasms↗

Response criteria for the prostate of the USA National Prostatic Cancer Project.

Response criteria developed by the national Prostatic Cancer Project to evaluate chemotherapy for advanced disease and as an adjuvant in early disease are described. Subjective and objective procedures and tests are used to compare pre- and post-treatment disease activity in advanced disease. These patients enter trials in demonstrated progression; hence stabilization of activity was considered a category of objective response. Other response categories include the rare complete response and less rare partial regression, with progression for non-responders. In adjuvant studies response indicators are the incidence of recurring disease and length of disease-free-interval.

Antineoplastic Agents↗

Value of new fluorescent immunoassay for human prostatic acid phosphatase in prostate cancer.

A new solid phase fluorescent immunoassay for human prostatic acid phosphatase in prostatic cancer has been evaluated. This technique is rapid, quantitative, and sensitive. In more than 133 patients studied by the National Prostatic Cancer Project, positive results were obtained in patients with localized, nonmetastatic disease as confirmed by clinical testing, surgical staging, and careful inspection of all pelvi lymph node material in appropriate cases. That this can occur even in Stage A2 patients may alter current concepts on the staging or, even further, on the therapy of prostatic cancer.

Acid Phosphatase↗