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The Pure Antiandrogen RU 23908 (Anandron), a Candidate of Choice for the Combined Antihormonal Treatment of Prostatic Cancer: A Review
ONCOLOGY AND CHEMOTHERAPY
Biological characteristics, prognostic factors, staging procedures, therapy and experimental models in prostatic cancer are summarized and reviewed. The author studied the question of to what degree does therapy improve prognosis in prostatic cancer. In his experience with stage B prostatic cancer external beam irradiation in the range of 6,000 to 6,500 rad will result in a less than 10 per cent pelvic recurrence rate. On the other hand, for stage C lesions external beam irradiation of 7,000 rad will lead to a 25 per cent incidence of pelvic recurrence. The use of computerized tomography is helpful to plan dosimetry and radiation fields. Lastly, if the primary prostatic lesion decreases by 50 per cent or more at 3 months after completion of external beam irradiation therapy, such patients will exhibit decreased rates of local recurrence and distant metastases. J.D.S. 11 figures, 1 table, 68 references
International Trends in Prostatic Cancer
D. G. ZARIDZE, P. BOYLE AND M. SMANS, Units of Analytical Epidemiology and Descriptive Epidemiology, International Agency for Research on Cancer, Lyon, France Int. J. Cancer, 33: 223-230 (Feb.) 1984 Incidence and mortality data through 1982 are presented, with the incidence data reflecting latent and clinical cases. Increased incidence rates were reported in the United States, Canada, Scandinavia (particularly Sweden) and Polynesia. The incidence rate has increased in black compared to white male patients in the same geographic areas of the United States. There has been a decreased incidence in the Orient, particularly in Japan, Singapore and the People's Republic of China. Time trends show that the incidence of prostatic cancer generally is increasing everywhere but at a greater rate in black compared to white patients in the United States. Mortality for prostatic cancer is highest in St. Vincent, and the Grenadines, Martinique and Bermuda. Mortality for prostatic cancer is lowest in the Orient, Colombia, Mexico and Egypt. Time trends again show that the mortality for prostatic cancer is increasing in most areas. In the United States the mortality for prostatic cancer is stable for white men but it is particularly high for black men more than 65 years old. The over-all conclusions from this large amount of data are: 1) there are large geographic variations in incidence with a 120fold difference between extremes, 2) the incidence and mortality of patients with prostatic cancer are increasing, especially in the areas that previously had reported a low incidence, 3) the increase in mortality from this disease usually is seen in patients more than 65 years old and 4) the ratio of mortality to incidence is variable, perhaps related to better treatment, increased survival following treatment, stage of diagnosis, racial differences and differences in diagnostic practices in various countries. Lastly, an increased awareness of latent prostatic cancer may result in an increased detection rate whether at prostatectomy or at autopsy. J. D. S. 2 figures, 5 tables, 15 references
The Pure Antiandrogen RU 23908 (Anandron), a Candidate of Choice for the Combined Antihormonal Treatment of Prostatic Cancer: A Review
J. P.
RAYNAUD, C. BONNE, M. MOGUILEWSKY, F. A. LEFEBVRE, A. BELANGER AND F. LABRIE, Roussel
UCLAF, Paris, France and Le Centre Hospitalier de l'Universite Laval, Quebec, Canada
1065
Prostate, 5: 299-311, 1984 RU 23908 is a pure antiandrogen that offers the possibility to study the effect of complete androgen neutralization and is a component of a new combined hormonal approach for the treatment of prostatic cancer in men. Antiandrogens acting at the receptor level have been proved effective in neutralizing the action of exogenous androgens in castrated animals. However, antiandrogens alone exert only a partial inhibition of prostate and seminal vesicle weight in intact animals, which is owing to the fact that pure antiandrogen neutralizes the inhibitory feedback effect of androgens at the pituitary level on the luteinizing hormone responsiveness to luteinizing hormonereleasing hormone. The authors suggest that luteinizing hormone-releasing hormone agonists, which induce a reversible castration, always should be given in combination with an antiandrogen to obtain an optimal inhibitory effect on the prostate as well as an inhibition of the luteinizing hormone responsiveness to luteinizing hormone-releasing hormone. As confirmed by preliminary pharmacokinetic studies RU 23908 possesses an antiandrogenic molecule that is devoid of any agonistic hormonal effect. The drug does not induce methemoglobinemia and its structure is stable enough to remain in its active form in the circulation for long intervals to achieve a constant supply of the competitor at the receptor site in the prostatic tumor. F. T. A. 13 figures, 30 references
Decreased Serum Phosphate Levels After High-Dose Estrogens in Metastatic Prostate Cancer. Possible Implications D. L. CITRIN, P. ELSON, M. S. KIES AND R. LIND, Department of Medicine and Cancer Center, Northwestern University Medical Center and Veterans Administration Lakeside Medical Center, Chicago, Illinois, and the Division of Biostatistics, Dana Farber Cancer Institute, Boston, Massachusetts Amer. J. Med., 76: 787-793 (May) 1984 Patients with metastatic prostatic cancer unresponsive to conventional doses of diethylstilbestrol have been reported to show response to massive doses (1 gm. per day of intravenous diethylstilbestrol diphosphate). While on treatment, these patients showed significant decreases in serum phosphate levels. The authors attempted to determine if the decrease in serum phosphate was indeed owing to diethylstilbestrol diphosphate. The data from several similar groups of patients treated with chemotherapy alone or combined with hormonal therapy that included diethylstilbestrol diphosphate were examined. A significant decrease was found only in patients treated with diethylstilbestrol diphosphate and not in those treated with chemotherapy alone. The maximal decrease was seen within 6 weeks after therapy had been initiated. After cessation of diethylstilbestrol diphosphate there generally was a rapid return of serum phosphate to normal levels. The hypophosphatemia that was recorded in these patients was only moderate and produced no obvious symptoms. It appears likely that the lowering of serum phosphate observed in these patients resulted from increased renal phosphate excretion associated with estrogen therapy. It is suggested that estrogens may induce renal phosphate leakage. It also has been suggested that prostatic cancer may cause tumor-induced osteomalacia by excreting a phosphaturic factor. The authors concluded that hypophosphatemia and, possibly, osteomalacia, which have been described in patients with met-
Biological characteristics, prognostic factors, staging procedures, therapy and experimental models in prostatic cancer are summarized and reviewed. The author studied the question of to what degree does therapy improve prognosis in prostatic cancer. In his experience with stage B prostatic cancer external beam irradiation in the range of 6,000 to 6,500 rad will result in a less than 10 per cent pelvic recurrence rate. On the other hand, for stage C lesions external beam irradiation of 7,000 rad will lead to a 25 per cent incidence of pelvic recurrence. The use of computerized tomography is helpful to plan dosimetry and radiation fields. Lastly, if the primary prostatic lesion decreases by 50 per cent or more at 3 months after completion of external beam irradiation therapy, such patients will exhibit decreased rates of local recurrence and distant metastases. J.D.S. 11 figures, 1 table, 68 references
International Trends in Prostatic Cancer
D. G. ZARIDZE, P. BOYLE AND M. SMANS, Units of Analytical Epidemiology and Descriptive Epidemiology, International Agency for Research on Cancer, Lyon, France Int. J. Cancer, 33: 223-230 (Feb.) 1984 Incidence and mortality data through 1982 are presented, with the incidence data reflecting latent and clinical cases. Increased incidence rates were reported in the United States, Canada, Scandinavia (particularly Sweden) and Polynesia. The incidence rate has increased in black compared to white male patients in the same geographic areas of the United States. There has been a decreased incidence in the Orient, particularly in Japan, Singapore and the People's Republic of China. Time trends show that the incidence of prostatic cancer generally is increasing everywhere but at a greater rate in black compared to white patients in the United States. Mortality for prostatic cancer is highest in St. Vincent, and the Grenadines, Martinique and Bermuda. Mortality for prostatic cancer is lowest in the Orient, Colombia, Mexico and Egypt. Time trends again show that the mortality for prostatic cancer is increasing in most areas. In the United States the mortality for prostatic cancer is stable for white men but it is particularly high for black men more than 65 years old. The over-all conclusions from this large amount of data are: 1) there are large geographic variations in incidence with a 120fold difference between extremes, 2) the incidence and mortality of patients with prostatic cancer are increasing, especially in the areas that previously had reported a low incidence, 3) the increase in mortality from this disease usually is seen in patients more than 65 years old and 4) the ratio of mortality to incidence is variable, perhaps related to better treatment, increased survival following treatment, stage of diagnosis, racial differences and differences in diagnostic practices in various countries. Lastly, an increased awareness of latent prostatic cancer may result in an increased detection rate whether at prostatectomy or at autopsy. J. D. S. 2 figures, 5 tables, 15 references
The Pure Antiandrogen RU 23908 (Anandron), a Candidate of Choice for the Combined Antihormonal Treatment of Prostatic Cancer: A Review
J. P.
RAYNAUD, C. BONNE, M. MOGUILEWSKY, F. A. LEFEBVRE, A. BELANGER AND F. LABRIE, Roussel
UCLAF, Paris, France and Le Centre Hospitalier de l'Universite Laval, Quebec, Canada
1065
Prostate, 5: 299-311, 1984 RU 23908 is a pure antiandrogen that offers the possibility to study the effect of complete androgen neutralization and is a component of a new combined hormonal approach for the treatment of prostatic cancer in men. Antiandrogens acting at the receptor level have been proved effective in neutralizing the action of exogenous androgens in castrated animals. However, antiandrogens alone exert only a partial inhibition of prostate and seminal vesicle weight in intact animals, which is owing to the fact that pure antiandrogen neutralizes the inhibitory feedback effect of androgens at the pituitary level on the luteinizing hormone responsiveness to luteinizing hormonereleasing hormone. The authors suggest that luteinizing hormone-releasing hormone agonists, which induce a reversible castration, always should be given in combination with an antiandrogen to obtain an optimal inhibitory effect on the prostate as well as an inhibition of the luteinizing hormone responsiveness to luteinizing hormone-releasing hormone. As confirmed by preliminary pharmacokinetic studies RU 23908 possesses an antiandrogenic molecule that is devoid of any agonistic hormonal effect. The drug does not induce methemoglobinemia and its structure is stable enough to remain in its active form in the circulation for long intervals to achieve a constant supply of the competitor at the receptor site in the prostatic tumor. F. T. A. 13 figures, 30 references
Decreased Serum Phosphate Levels After High-Dose Estrogens in Metastatic Prostate Cancer. Possible Implications D. L. CITRIN, P. ELSON, M. S. KIES AND R. LIND, Department of Medicine and Cancer Center, Northwestern University Medical Center and Veterans Administration Lakeside Medical Center, Chicago, Illinois, and the Division of Biostatistics, Dana Farber Cancer Institute, Boston, Massachusetts Amer. J. Med., 76: 787-793 (May) 1984 Patients with metastatic prostatic cancer unresponsive to conventional doses of diethylstilbestrol have been reported to show response to massive doses (1 gm. per day of intravenous diethylstilbestrol diphosphate). While on treatment, these patients showed significant decreases in serum phosphate levels. The authors attempted to determine if the decrease in serum phosphate was indeed owing to diethylstilbestrol diphosphate. The data from several similar groups of patients treated with chemotherapy alone or combined with hormonal therapy that included diethylstilbestrol diphosphate were examined. A significant decrease was found only in patients treated with diethylstilbestrol diphosphate and not in those treated with chemotherapy alone. The maximal decrease was seen within 6 weeks after therapy had been initiated. After cessation of diethylstilbestrol diphosphate there generally was a rapid return of serum phosphate to normal levels. The hypophosphatemia that was recorded in these patients was only moderate and produced no obvious symptoms. It appears likely that the lowering of serum phosphate observed in these patients resulted from increased renal phosphate excretion associated with estrogen therapy. It is suggested that estrogens may induce renal phosphate leakage. It also has been suggested that prostatic cancer may cause tumor-induced osteomalacia by excreting a phosphaturic factor. The authors concluded that hypophosphatemia and, possibly, osteomalacia, which have been described in patients with met-