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Treatment With Gonadotrophin Releasing Hormone Analogue in Advanced Prostatic Cancer
1019
Ol'
Development of an_ In Vitro Cfonogenic Assay for the R3327 Rat P_rostatic Adenocarci.noma Permits Comparison of the Proliferative Potential of the R3327, R3327 A, and R3327 AT Tumors
J_ J_ DrnNER AND A_ NAKEFF, Section of Cancer Biology, Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St_ Louis, Missouri Prostate, 4: 289-306, 1983 The Dunning rat prostate tumor (R3327) is a unique, experimental model system for human tumors since it 1) represents 1 of only a few spontaneously occurring prostatic carcinomas in laboratory animals that, despite its being transplanted in vivo for > 15 years, still retains the well differentiated and characteristically acinar prostatic epithelium, 2) grows slowly, 3) is responsive to steroid hormone control, 4) is similar to human prostatic carcinoma histologically, histochemically and biochemically, and 5) exists in several different histological categories_ The R3327G grows rapidly and the R3327H grows slowly but both remain hormone responsive_ Two other tumors are hormone-independent and grow rapidly: the R3327A squamous cell carcinoma and the R3327 AT spindle cell carcinoma_ The authors have developed an in vitro clonogenic cell assay to measure and compare systematically the proliferative poten tial of these tumors following various monodispersion techniques_ Linear relationships between the number of monodispersed tumor cells cultured at low cell density and the number of colonies formed 10 days later establish these assays as the first quantitative cellular approach to those proliferative subpopulations responsible ultimately for the growth of these tumors_ The authors have chosen the name colony-forming cellprostatic adenocarcinoma to refer to the members of the proliferative subpopulation of the R3327 tumor. An ultrastructural comparison of R3327 adenocarcinoma tissue sections with the cells produced during culture provides evidence that the cells of the proliferative subpopulation may be derived from the acinar epithelium of the tumor. W W K 7 figures, 2 tables, 28 references
Treatment With Gm:1.adotrophin Releasing H,wmone Analogue in Advanced Prostatic Cancer J_ H_ WHITFIELD,
J_ A_ l--L G. IvL BESSER, J_
Brit_ Med. J., 286: 1309-1312
W. F_
s_
MALPAS AND
l--L N_ R. T. D_ and
23) 1983
Gonadotropin -releasing hormone originates in the hypothalamus and releases luteinizing and follicle-stimulating hormones from the pituitary gland. Its release from the hypothalamus is pulsatile and this pulsatility is important for the synthesis and the secretion of the gonadotropins by the pituitary_ The mechanism of long-acting gonadotropin-releasing hormone analogues, with their greatly enhanced potency, is paradoxicaL After initial stimulation down regulation of the pituitary and, finally, the gonad also occurs, resulting from the prolonged binding of the analogues to pituitary receptors_ This role in suppressing gonadal activity presently is being examined as a means of treatment of metastatic prostatic cancer_ The authors report on 12 patients with histologically proved
advanced prostatic cancer that was untreated previously_ Of the patients 2 had stage C prostate cancer and 10 had stage D carcinoma_ Eight patients had positive bone scans_ Subjects received 200 µ.g_ buserelin intranasally 5 times daily for l to 9 months_ Testosterone concentrations compatible with castration were reached by treatment week 4_ Of the 12 patients 9 had objective and subjective signs of regression of disease_ Acid phosphatase initially was increased in 6 patients and became normal in 5. Of the 8 patients with initially abnormal bone scans 4 had improvement with treatment but none achieved a normal scan_ Of 9 patients with pre-treatment and post-treatment computerized tomographic scans 6 showed objective improvement_ All patients became impotent on therapy_ They also noticed facial flushing from 1 to 6 times daily_ The authors conclude that buserelin is as effective, at least in the short-term, as estrogen or orchiectomy_ p_ M_ H 2 figures, 2 tables, 21 references
An EORTC Phase II Study of Vindesine i.n Advanced Prostate Cancer
w_
G. JoNEs,
A_
s_ o_
FossA, L DENIS, p_ CoNrnx, K
M.
w_
University Department of Radiotherapy, Cookridge Hospital, Leeds, United Kingdom, General Department, Norwegian Radium Hospital, Montebello, Oslo, Department of Urology, Middleheim Ziekenhuis, Lindendreef, Antwerp, Belgium, Centre Jean Godinot, Rheims, France, Department of Urology, Huddersfield Royal Infirmary, Huddersfield, United Kingdom, Department of Urology, Hacettepe University, Ankara, Turkey and EORTC Data Centre, Institute Jules Bordet, Brussels, Belgium GLASHAN,
AKDAS AND
DEPAUW,
Eur_ J_ Cancer Clin_ OncoL, 19: 583-588 (May) 1983
Anecdotal reports concerning the use of vindesine in patients with prostatic cancer has prompted this phase II study of vindesine in patients with primary or metastatic disease that was measurable in 2 dimensions_ Patients were given 2 mg-/ m_ 2 weekly for at least 4 treatment cycles: 5 (19 per cent) achieved a partial remission of short duration, 11 (41 per cent) had no changes and 11 per cent) had pnJgres1noi11_ Therefore, an objective response of 19 per cent has been reported in this When these results are compared to 24 per cent for platinum and 23 per cent for doxorubicin one may conclude that when the and low yield for vindesine are considered it is unlikely that this drug will have any significant role in the management of prostatic cancer_ N_ J. 1 figure, 4 tables, 14 references
Conveniion of a Novel 5-FluorouracH (5-JFU) Derivative to 5-FU in Rats
K
TAKADA,
R
YOSHIKAWA ANDS. MURANISHI,
Kyoto College
of Pharmacy, Yamashina, Kyoto, Japan Res_ Comm Chem_ Path_ Pharm_, 40: 99-108 (Apr_) 1983 The converting efficiency of a new 5-fluorouracil derivative, 1,3- didecanoyl- 2- (6-((5-fluorouracil-l-yl)carbonylamino ]hexanoyl glyceride (DFUG), to 5-fluorouracil was investigated in conjunction with plasma concentration in rats_ DFUG was designed as a pro-drug of 5-fluorouracil that releases 5-fluorouracil by entering into the systemic circulation_ The conver-
Ol'
Development of an_ In Vitro Cfonogenic Assay for the R3327 Rat P_rostatic Adenocarci.noma Permits Comparison of the Proliferative Potential of the R3327, R3327 A, and R3327 AT Tumors
J_ J_ DrnNER AND A_ NAKEFF, Section of Cancer Biology, Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St_ Louis, Missouri Prostate, 4: 289-306, 1983 The Dunning rat prostate tumor (R3327) is a unique, experimental model system for human tumors since it 1) represents 1 of only a few spontaneously occurring prostatic carcinomas in laboratory animals that, despite its being transplanted in vivo for > 15 years, still retains the well differentiated and characteristically acinar prostatic epithelium, 2) grows slowly, 3) is responsive to steroid hormone control, 4) is similar to human prostatic carcinoma histologically, histochemically and biochemically, and 5) exists in several different histological categories_ The R3327G grows rapidly and the R3327H grows slowly but both remain hormone responsive_ Two other tumors are hormone-independent and grow rapidly: the R3327A squamous cell carcinoma and the R3327 AT spindle cell carcinoma_ The authors have developed an in vitro clonogenic cell assay to measure and compare systematically the proliferative poten tial of these tumors following various monodispersion techniques_ Linear relationships between the number of monodispersed tumor cells cultured at low cell density and the number of colonies formed 10 days later establish these assays as the first quantitative cellular approach to those proliferative subpopulations responsible ultimately for the growth of these tumors_ The authors have chosen the name colony-forming cellprostatic adenocarcinoma to refer to the members of the proliferative subpopulation of the R3327 tumor. An ultrastructural comparison of R3327 adenocarcinoma tissue sections with the cells produced during culture provides evidence that the cells of the proliferative subpopulation may be derived from the acinar epithelium of the tumor. W W K 7 figures, 2 tables, 28 references
Treatment With Gm:1.adotrophin Releasing H,wmone Analogue in Advanced Prostatic Cancer J_ H_ WHITFIELD,
J_ A_ l--L G. IvL BESSER, J_
Brit_ Med. J., 286: 1309-1312
W. F_
s_
MALPAS AND
l--L N_ R. T. D_ and
23) 1983
Gonadotropin -releasing hormone originates in the hypothalamus and releases luteinizing and follicle-stimulating hormones from the pituitary gland. Its release from the hypothalamus is pulsatile and this pulsatility is important for the synthesis and the secretion of the gonadotropins by the pituitary_ The mechanism of long-acting gonadotropin-releasing hormone analogues, with their greatly enhanced potency, is paradoxicaL After initial stimulation down regulation of the pituitary and, finally, the gonad also occurs, resulting from the prolonged binding of the analogues to pituitary receptors_ This role in suppressing gonadal activity presently is being examined as a means of treatment of metastatic prostatic cancer_ The authors report on 12 patients with histologically proved
advanced prostatic cancer that was untreated previously_ Of the patients 2 had stage C prostate cancer and 10 had stage D carcinoma_ Eight patients had positive bone scans_ Subjects received 200 µ.g_ buserelin intranasally 5 times daily for l to 9 months_ Testosterone concentrations compatible with castration were reached by treatment week 4_ Of the 12 patients 9 had objective and subjective signs of regression of disease_ Acid phosphatase initially was increased in 6 patients and became normal in 5. Of the 8 patients with initially abnormal bone scans 4 had improvement with treatment but none achieved a normal scan_ Of 9 patients with pre-treatment and post-treatment computerized tomographic scans 6 showed objective improvement_ All patients became impotent on therapy_ They also noticed facial flushing from 1 to 6 times daily_ The authors conclude that buserelin is as effective, at least in the short-term, as estrogen or orchiectomy_ p_ M_ H 2 figures, 2 tables, 21 references
An EORTC Phase II Study of Vindesine i.n Advanced Prostate Cancer
w_
G. JoNEs,
A_
s_ o_
FossA, L DENIS, p_ CoNrnx, K
M.
w_
University Department of Radiotherapy, Cookridge Hospital, Leeds, United Kingdom, General Department, Norwegian Radium Hospital, Montebello, Oslo, Department of Urology, Middleheim Ziekenhuis, Lindendreef, Antwerp, Belgium, Centre Jean Godinot, Rheims, France, Department of Urology, Huddersfield Royal Infirmary, Huddersfield, United Kingdom, Department of Urology, Hacettepe University, Ankara, Turkey and EORTC Data Centre, Institute Jules Bordet, Brussels, Belgium GLASHAN,
AKDAS AND
DEPAUW,
Eur_ J_ Cancer Clin_ OncoL, 19: 583-588 (May) 1983
Anecdotal reports concerning the use of vindesine in patients with prostatic cancer has prompted this phase II study of vindesine in patients with primary or metastatic disease that was measurable in 2 dimensions_ Patients were given 2 mg-/ m_ 2 weekly for at least 4 treatment cycles: 5 (19 per cent) achieved a partial remission of short duration, 11 (41 per cent) had no changes and 11 per cent) had pnJgres1noi11_ Therefore, an objective response of 19 per cent has been reported in this When these results are compared to 24 per cent for platinum and 23 per cent for doxorubicin one may conclude that when the and low yield for vindesine are considered it is unlikely that this drug will have any significant role in the management of prostatic cancer_ N_ J. 1 figure, 4 tables, 14 references
Conveniion of a Novel 5-FluorouracH (5-JFU) Derivative to 5-FU in Rats
K
TAKADA,
R
YOSHIKAWA ANDS. MURANISHI,
Kyoto College
of Pharmacy, Yamashina, Kyoto, Japan Res_ Comm Chem_ Path_ Pharm_, 40: 99-108 (Apr_) 1983 The converting efficiency of a new 5-fluorouracil derivative, 1,3- didecanoyl- 2- (6-((5-fluorouracil-l-yl)carbonylamino ]hexanoyl glyceride (DFUG), to 5-fluorouracil was investigated in conjunction with plasma concentration in rats_ DFUG was designed as a pro-drug of 5-fluorouracil that releases 5-fluorouracil by entering into the systemic circulation_ The conver-