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Investigation of the Combination of the Agonist D-Trp-6-LH-RH and the Antiandrogen Flutamide in the Treatment of Dunning R-3327H Prostate Cancer Model
633
ONCOLOGY AND CHEMOTHERAPY
Evidence for a direct relationship between herpesvirus infection and human cancer has been reported previously. Virological and epidemiological studies suggest a correlation between human cytomegalovirus as a possible etiological agent in patients with prostatic cancer. A murine monoclonal antibody is described that binds to a surface antigen in prostatic and bladder tumors. The preliminary results indicate that the monoclonal antibody cross-reacts with human cells that have been transformed by human cytomegalovirus. The authors concluded that D83.21 reacts with a "common cell surface protein" expressed on human cytomegalovirus-transformed cells and urogenital tumors. N. J. 1 figure, 2 tables, 29 references
Investigation of the Combination of the Agonist D-Trp6-LH-RH and the Antiandrogen Flutamide in the Treatment of Dunning R-3327H Prostate Cancer Model
T. W. REDDING AND A. V. SCHALLY, Endocrine and Polypeptide Laboratory, Veterans Administration Medical Center and Department of Medicine, Tulane University Sclwol of Medicine, New Orleans, Louisiana Prostate, 6: 219-232, 1985 The therapy for patients with prostatic cancer and other sex steroid-dependent tumors based on agonists of luteinizing hormone-releasing hormone (LH-RH) has been made more practical and efficacious by the development of a long-acting formulation of microcapsules of D-Trp-6-LH-RH for controlled release. Antiandrogens, which neutralize the effect of endogenous androgens, also have been used in the management of prostatic cancer in man. The effects of a simultaneous administration of the antiandrogen flutamide and microcapsules of the agonist D-Trp-6-LH-RH were studied in the Dunning R3327H rat prostatic adenocarcinoma model to determine whether the combination of these 2 drugs might inhibit tumor growth more effectively than single agents. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 gm. per day for 30 days, were injected intramuscularly once a month. Flutamide was administered subcutaneously at a daily dose of 25 mg./kg. The therapy was started 100 days after the tumor transplantation and continued for 60 days. Tumor weights and volumes were reduced significantly in rats treated with microcapsules or flutamide alone but the former drug inhibited tumor growth more than the latter. The combined treatment of flutamide and microcapsules significantly decreased tumor weight and volume but did not exert a synergistic effect on tumor growth, the reduction being smaller for the combination than for the microcapsules alone. There was a significant elevation of serum testosterone, luteinizing hormone and prolactin in rats treated with flutamide. On the other hand, in rats given microcapsules of D-Trp-6-LHRH, testosterone decreased to castration levels within 7 days and remained at nondetectable values, serum luteinizing hormone and prolactin levels also being suppressed in this group. The combined administration of microcapsules and flutamide also significantly decreased serum testosterone to nondetectable levels by day 7, and suppressed serum luteinizing hormone and prolactin. These findings raised doubts of whether the daily administration of the combination of LH -RH agonist with an antiandrogen offers an advantage over the use of microcapsules of an agonist, such as D-Trp-6-LH-RH, alone in
the treatment of prostatic carcinoma. 1 figure, 4 tables, 66 references
W. W. K.
High Serum Prolactin Associated With Poor Prognosis in Carcinoma of the Prostate A. D. MEE, 0. KHAN AND K. MASHITER, Departments of Urology, Charing Cross Hospital and Hammersmith Hospital, London, England
Brit. J. Urol., 56: 698-701 (Dec.) 1984 Since treatment of patients with prostatic cancer using estrogens and antiandrogens results in increased serum prolactin levels, the authors questioned whether the resultant promotion of uptake and metabolism of testosterone in the prostate would have an adverse effect on the disease. Blood specimens were drawn in 71 patients for serum prolactin activity in the morning every 2 to 3 months, with the prolactin activity performed via a double antibody radioimmunoassay method. Patients were considered as to be stable or having progressive disease based on the pain status, urinary obstruction or doubling of serum acid phosphatase levels. Treatments included 1 mg. diethylstilbestrol 3 times daily in 33 patients, 100 mg. cyproterone 3 times daily in 14, 560 mg. estramustine phosphate per day in 5 and bilateral orchiectomy in 13. Of the 71 patients 21 had at least 1 elevation of serum prolactin. Increased serum prolactin was seen in 10 of 17 patients (59 per cent) with progressive disease. Of the latter 10 patients 7 have died, while the 7 with normal prolactin level are alive. Elevated serum prolactin was seen in 11 of 54 patients (20 per cent) with stable disease and 3 have died compared to only 2 of 43 with normal prolactin activity. Over-all, increased serum prolactin was seen in 10 of the 12 patients who died. Considering treatment groups, increased serum prolactin was seen in 47 per cent of the patients treated with diethylstilbestrol or cyproterone. It is recommended that hormonal therapy be switched to orchiectomy if a patient shows an increase in serum prolactin levels. Alternative treatments include the use of the prolactin antagonist bromocryptine or the use of a luteinizing hormonereleasing hormone agonist. J. D. S. 2 figures, 15 references
Differential Diagnosis of Kaposi's Sarcoma
W. BLUMENFELD, B. M. EGBERT AND R. W. 8AGEBIEL, Department of Pathology, University of California Medical Center, San Francisco, California Arch. Path. Lab. Med., 109: 123-127 (Feb.) 1985 The pathological features of Kaposi's sarcoma were reviewed. During a 15-month period 106 lesions were biopsied to rule out Kaposi's sarcoma. The diagnosis was confirmed in 40 cases (38 per cent). A second group consisting of dermatofibromas, hemangiomas and scars comprised 56 per cent of the series (59 cases). Atypical vascular lesions with insufficient criteria for a diagnosis of Kaposi's sarcoma were encountered in 7 instances. Abnormally shaped, irregular vessels were the best criterion to diagnose early Kaposi's sarcoma. Nodular lesions with slit-like vascular channels and peripheral vessels similar to early lesions were seen later in the course of the disease. J. H. N. 5 figures, 1 table, 24 references
ONCOLOGY AND CHEMOTHERAPY
Evidence for a direct relationship between herpesvirus infection and human cancer has been reported previously. Virological and epidemiological studies suggest a correlation between human cytomegalovirus as a possible etiological agent in patients with prostatic cancer. A murine monoclonal antibody is described that binds to a surface antigen in prostatic and bladder tumors. The preliminary results indicate that the monoclonal antibody cross-reacts with human cells that have been transformed by human cytomegalovirus. The authors concluded that D83.21 reacts with a "common cell surface protein" expressed on human cytomegalovirus-transformed cells and urogenital tumors. N. J. 1 figure, 2 tables, 29 references
Investigation of the Combination of the Agonist D-Trp6-LH-RH and the Antiandrogen Flutamide in the Treatment of Dunning R-3327H Prostate Cancer Model
T. W. REDDING AND A. V. SCHALLY, Endocrine and Polypeptide Laboratory, Veterans Administration Medical Center and Department of Medicine, Tulane University Sclwol of Medicine, New Orleans, Louisiana Prostate, 6: 219-232, 1985 The therapy for patients with prostatic cancer and other sex steroid-dependent tumors based on agonists of luteinizing hormone-releasing hormone (LH-RH) has been made more practical and efficacious by the development of a long-acting formulation of microcapsules of D-Trp-6-LH-RH for controlled release. Antiandrogens, which neutralize the effect of endogenous androgens, also have been used in the management of prostatic cancer in man. The effects of a simultaneous administration of the antiandrogen flutamide and microcapsules of the agonist D-Trp-6-LH-RH were studied in the Dunning R3327H rat prostatic adenocarcinoma model to determine whether the combination of these 2 drugs might inhibit tumor growth more effectively than single agents. Microcapsules of D-Trp-6-LH-RH, calculated to release a controlled dose of 25 gm. per day for 30 days, were injected intramuscularly once a month. Flutamide was administered subcutaneously at a daily dose of 25 mg./kg. The therapy was started 100 days after the tumor transplantation and continued for 60 days. Tumor weights and volumes were reduced significantly in rats treated with microcapsules or flutamide alone but the former drug inhibited tumor growth more than the latter. The combined treatment of flutamide and microcapsules significantly decreased tumor weight and volume but did not exert a synergistic effect on tumor growth, the reduction being smaller for the combination than for the microcapsules alone. There was a significant elevation of serum testosterone, luteinizing hormone and prolactin in rats treated with flutamide. On the other hand, in rats given microcapsules of D-Trp-6-LHRH, testosterone decreased to castration levels within 7 days and remained at nondetectable values, serum luteinizing hormone and prolactin levels also being suppressed in this group. The combined administration of microcapsules and flutamide also significantly decreased serum testosterone to nondetectable levels by day 7, and suppressed serum luteinizing hormone and prolactin. These findings raised doubts of whether the daily administration of the combination of LH -RH agonist with an antiandrogen offers an advantage over the use of microcapsules of an agonist, such as D-Trp-6-LH-RH, alone in
the treatment of prostatic carcinoma. 1 figure, 4 tables, 66 references
W. W. K.
High Serum Prolactin Associated With Poor Prognosis in Carcinoma of the Prostate A. D. MEE, 0. KHAN AND K. MASHITER, Departments of Urology, Charing Cross Hospital and Hammersmith Hospital, London, England
Brit. J. Urol., 56: 698-701 (Dec.) 1984 Since treatment of patients with prostatic cancer using estrogens and antiandrogens results in increased serum prolactin levels, the authors questioned whether the resultant promotion of uptake and metabolism of testosterone in the prostate would have an adverse effect on the disease. Blood specimens were drawn in 71 patients for serum prolactin activity in the morning every 2 to 3 months, with the prolactin activity performed via a double antibody radioimmunoassay method. Patients were considered as to be stable or having progressive disease based on the pain status, urinary obstruction or doubling of serum acid phosphatase levels. Treatments included 1 mg. diethylstilbestrol 3 times daily in 33 patients, 100 mg. cyproterone 3 times daily in 14, 560 mg. estramustine phosphate per day in 5 and bilateral orchiectomy in 13. Of the 71 patients 21 had at least 1 elevation of serum prolactin. Increased serum prolactin was seen in 10 of 17 patients (59 per cent) with progressive disease. Of the latter 10 patients 7 have died, while the 7 with normal prolactin level are alive. Elevated serum prolactin was seen in 11 of 54 patients (20 per cent) with stable disease and 3 have died compared to only 2 of 43 with normal prolactin activity. Over-all, increased serum prolactin was seen in 10 of the 12 patients who died. Considering treatment groups, increased serum prolactin was seen in 47 per cent of the patients treated with diethylstilbestrol or cyproterone. It is recommended that hormonal therapy be switched to orchiectomy if a patient shows an increase in serum prolactin levels. Alternative treatments include the use of the prolactin antagonist bromocryptine or the use of a luteinizing hormonereleasing hormone agonist. J. D. S. 2 figures, 15 references
Differential Diagnosis of Kaposi's Sarcoma
W. BLUMENFELD, B. M. EGBERT AND R. W. 8AGEBIEL, Department of Pathology, University of California Medical Center, San Francisco, California Arch. Path. Lab. Med., 109: 123-127 (Feb.) 1985 The pathological features of Kaposi's sarcoma were reviewed. During a 15-month period 106 lesions were biopsied to rule out Kaposi's sarcoma. The diagnosis was confirmed in 40 cases (38 per cent). A second group consisting of dermatofibromas, hemangiomas and scars comprised 56 per cent of the series (59 cases). Atypical vascular lesions with insufficient criteria for a diagnosis of Kaposi's sarcoma were encountered in 7 instances. Abnormally shaped, irregular vessels were the best criterion to diagnose early Kaposi's sarcoma. Nodular lesions with slit-like vascular channels and peripheral vessels similar to early lesions were seen later in the course of the disease. J. H. N. 5 figures, 1 table, 24 references