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JUNIO 2.003
JUNE 2.003
THE FINASTERIDE IN
THE EYE OF THE STORM
1.)The Influence of Finasteride on the Development of Prostate
Cancer
2.) Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial.
3.) The effect of finasteride on the risk of acute urinary
retention and the need for surgical treatment among men with benign prostatic
hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.
4.) 5alpha-reductase inhibitors: what
role should they play?
5.) Cytologic atypia in a 53-year-old man with finasteride-induced
gynecomastia 6.)Case report: finasteride-induced gynecomastia in a 62-year-old man.
7.) Incidence and severity of sexual adverse experiences in finasteride and placebo-treated
men with benign prostatic hyperplasia.
8.) Droga para la calvicie (Finasteride) reduce riesgo de cáncer pero aconsejan
cautela
9.) Proscar: five-year experience
10.) Long-term (7 to 8-year) experience with finasteride in men with benign
prostatic hyperplasia.
1.) The Influence of Finasteride on the Development of Prostate
The Influence of Finasteride on the Development of Prostate Cancer
Source: http://www.nejm.org/
Ian M. Thompson, M.D., Phyllis J. Goodman, M.S., Catherine M. Tangen, Dr.P.H.,
M. Scott Lucia, M.D., Gary J. Miller, M.D., Ph.D., Leslie G. Ford, M.D., Michael
M. Lieber, M.D., R. Duane Cespedes, M.D., James N. Atkins, M.D., Scott M.
Lippman, M.D., Susie M. Carlin, B.A., Anne Ryan, R.N., Connie M. Szczepanek, R.N.,
B.S.N., John J. Crowley, Ph.D., and Charles A. Coltman, Jr., M.D.
ABSTRACT
Background Androgens are involved in the development of prostate cancer.
Finasteride, an inhibitor of 5-reductase, inhibits the conversion of
testosterone to dihydrotestosterone, the primary androgen in the prostate, and
may reduce the risk of prostate cancer.
Methods In the Prostate Cancer Prevention Trial, we randomly assigned 18,882 men
55 years of age or older with a normal digital rectal examination and a prostate-specific
antigen (PSA) level of 3.0 ng per milliliter or lower to treatment with
finasteride (5 mg per day) or placebo for seven years. Prostate biopsy was
recommended if the annual PSA level, adjusted for the effect of finasteride,
exceeded 4.0 ng per milliliter or if the digital rectal examination was abnormal.
It was anticipated that 60 percent of participants would have prostate cancer
diagnosed during the study or would undergo biopsy at the end of the study. The
primary end point was the prevalence of prostate cancer during the seven years
of the study.
Results Prostate cancer was detected in 803 of the 4368 men in the finasteride
group who had data for the final analysis (18.4 percent) and 1147 of the 4692
men in the placebo group who had such data (24.4 percent), for a 24.8 percent
reduction in prevalence over the seven-year period (95 percent confidence
interval, 18.6 to 30.6 percent; P<0.001). Tumors of Gleason grade 7, 8, 9, or 10
were more common in the finasteride group (280 of 757 tumors [37.0 percent], or
6.4 percent of the 4368 men included in the final analysis) than in the placebo
group (237 of 1068 tumors [22.2 percent], P<0.001 for the comparison between
groups; or 5.1 percent of the 4692 men included in the final analysis, P=0.005
for the comparison between groups). Sexual side effects were more common in
finasteride-treated men, whereas urinary symptoms were more common in men
receiving placebo.
Conclusions Finasteride prevents or delays the appearance of prostate cancer,
but this possible benefit and a reduced risk of urinary problems must be weighed
against sexual side effects and the increased risk of high-grade prostate cancer.
2.)
Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial
Study design of the Medical Therapy of Prostatic Symptoms (MTOPS) trial.
Control Clin Trials. 2003 Apr;24(2):224-43. Related Articles, Links
Bautista OM, Kusek JW, Nyberg LM, McConnell JD, Bain RP, Miller G, Crawford ED,
Kaplan SA, Sihelnik SA, Brawer MK, Lepor H.
George Washington University, Rockville, MD, USA
Alpha-blockers and 5-alpha-reductase inhibitors are medical therapies that are
being used as alternatives to surgical interventions to relieve symptoms of
benign prostatic hyperplasia (BPH). Taken as monotherapy, alpha-blockers and
5-alpha-reductase inhibitors have each been shown to provide relief from BPH
symptoms. Treatment with finasteride over 4 years has been shown to reduce both
BPH symptoms and the likelihood of acute urinary retention and the need for
surgery. Direct comparison of the alpha-blocker terazosin with finasteride has
been done, but only for a period of 1 year. The Medical Therapy of Prostatic
Symptoms (MTOPS) trial is a multicenter, randomized, placebo-controlled, double-masked
clinical trial designed to evaluate the long-term efficacy of the alpha-blocker
doxazosin and the 5-alpha-reductase inhibitor finasteride, whether taken as a
monotherapy or in combination, in preventing or delaying the progression of BPH.
We describe in this paper the design of the MTOPS trial, the concept of BPH
progression, the definition and methods of determining the primary outcome
events and the proposed statistical analysis methods. A unique feature of MTOPS
is the inclusion of prostate biopsies on a subgroup of randomized participants.
Volunteers among randomized participants are to undergo a biopsy of the prostate
at predetermined time points during the trial. Studies that will be conducted
using the tissue specimens collected in MTOPS can potentially provide
information at the molecular level on the natural history of BPH among medically
treated and untreated men with moderate to severe symptoms of BPH.
3.) The effect of finasteride on the risk of acute
urinary retention and the need for surgical treatment among men with benign
prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group.
Source: N Engl J Med. 1998
Feb 26;338(9):557-63.
Comment in:
ACP J Club. 1998 Jul-Aug;129(1):11.
N Engl J Med. 1998 Feb 26;338(9):612-3.
McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL,
Albertsen P, Roehrborn CG, Nickel JC, Wang DZ, Taylor AM, Waldstreicher J.
University of Texas Southwestern Medical Center, Dallas 75235-9110, USA.
BACKGROUND: Finasteride is known to improve urinary symptoms in men with benign
prostatic hyperplasia, but the extent to which the benefit is sustained and
whether finasteride reduces the incidence of related events, including the need
for surgery and the development of acute urinary retention, is not known.
METHODS: In this double-blind, randomized, placebo-controlled trial, we studied
3040 men with moderate-to-severe urinary symptoms and enlarged prostate glands
who were treated daily with 5 mg of finasteride or placebo for four years.
Symptom scores (on a scale of 1 to 34), urinary flow rates, and the occurrence
of outcome events were assessed every four months in 3016 men. Prostate volume
was measured in a subgroup of the men. Complete data on outcomes were available
for 2760 men. RESULTS: During the four-year study period, 152 of the 1503 men in
the placebo group (10 percent) and 69 of the 1513 men in the finasteride group
(5 percent) underwent surgery for benign prostatic hyperplasia (reduction in
risk with finasteride, 55 percent; 95 percent confidence interval, 41 to 65
percent). Acute urinary retention developed in 99 men (7 percent) in the placebo
group and 42 men (3 percent) in the finasteride group (reduction in risk with
finasteride, 57 percent; 95 percent confidence interval, 40 to 69 percent).
Among the men who completed the study, the mean decreases in the symptom score
were 3.3 in the finasteride group and 1.3 in the placebo group (P<0.001).
Treatment with finasteride also significantly improved urinary flow rates and
reduced prostate volume (P<0.001). CONCLUSIONS: Among men with symptoms of
urinary obstruction and prostatic enlargement, treatment with finasteride for
four years reduces symptoms and prostate volume, increases the urinary flow rate,
and reduces the risk of surgery and acute urinary retention.
4.) 5alpha-reductase inhibitors: what
role should they play?
Urology. 2001 Dec;58(6 Suppl 1):65-70; discussion 70.
Kaplan SA.
Department of Urology, Columbia University, New York, New York, USA.
The development of finasteride (PROSCAR, Merck & Co., Whitehouse Station, NJ)
for the treatment of benign prostatic hyperplasia (BPH) has had variable results.
Numerous short-term and long-term studies comparing finasteride with placebo
have been reported. The results suggest that, physiologically, treatment with
finasteride significantly decreases levels of both serum and intraprostatic
dihydrotestosterone about 70% to 80% from baseline. In addition, total gland
size decreases significantly-about 15% to 25% from baseline-particularly in the
area of the periurethral zone of the prostate after finasteride treatment.
Baseline prostate size has been found to have a relation to efficacy of
finasteride treatment. The larger the prostate at baseline, the greater the
urinary flow rate increase and symptom score decrease compared with placebo.
Health-related quality-of-life parameters improved in those taking finasteride.
In studies evaluating combination therapy, no significant differences were noted
between those treated with an alpha blocker, such as terazosin or doxazosin in
combination with finasteride, and those receiving an alpha blocker alone. Long-term
finasteride versus placebo studies, such as the PROSCAR Long-Term Efficacy and
Safety Study (PLESS), suggest that long-term medical therapy with finasteride
affects the natural history of the disease as manifested by the decrease in
rates of acute urinary retention and surgery. In patients who are "therapeutic
responders," the degree of symptomatic improvement in those treated with
finasteride appears to be equal to that seen in patients receiving alpha
blockers. Prostate cancer detection rates did not differ between those treated
with finasteride and those receiving a placebo. The results of these studies
suggest that physicians must evaluate what role finasteride plays in the
spectrum of available options for the treatment of BPH and lower urinary tract
symptoms. Baseline parameters, such as prostate volume, prostate-specific
antigen values, and whether to administer finasteride in combination with alpha
blockers, are among the factors that will determine the appropriateness of such
therapy.
5.)
Cytologic atypia in a 53-year-old man with finasteride-induced
gynecomastia
Cytologic atypia in a 53-year-old man with finasteride-induced
gynecomastia.
Arch Pathol Lab Med. 2000 Apr;124(4):625-7.
Zimmerman RL, Fogt F, Cronin D, Lynch R.
Departments of Pathology & Laboratory Medicine, Presbyterian Medical Center,
University of Pennsylvania Health System, Philadelphia, PA 19104, USA.
Finasteride has been associated with the development of gynecomastia. Although
cytoplasmic vacuolization has been noted in prostatic epithelium in men taking
this drug, we found no documentation of the cytologic changes in finasteride-associated
gynecomastia. We present the case of a 53-year-old man who developed unilateral
gynecomastia following finasteride therapy for alopecia. A fine-needle
aspiration biopsy of the mass was diagnosed as adenocarcinoma on the basis of
nuclear atypia and particularly because of cytoplasmic vacuolization. Subsequent
excisional biopsy revealed benign gynecomastia with no evidence of malignant
change. The ductal epithelium did exhibit cytoplasmic vacuolization similar to
that described in the prostate following finasteride therapy. We believe this is
the first reported case documenting the cytologic changes seen in gynecomastia
secondary to finasteride therapy. Cytoplasmic vacuolization in this setting
should not be considered evidence of malignancy in men with gynecomastia. As
with gynecomastia in general, extreme caution should be used before rendering a
cytologic diagnosis of malignancy.
6.)Case report: finasteride-induced gynecomastia in a 62-year-old man.
Am J Med Sci. 1995 Jun;309(6):322-5.
Volpi R, Maccarini PA, Boni S, Chiodera P, Coiro V.
Department of Medicine, University of Parma, Italy.
The authors describe a case of bilateral (with left prevalence) gynecomastia in
a 62-year-old man after finasteride treatment because of benign prostatic
hypertrophy. Finasteride is an inhibitor of 5 alpha-reductase, the enzyme
responsible for testosterone metabolism to dihydrotestosterone. In this patient,
nonspecific endocrine alterations were found, except for a significant decrease
in dihydrotestosterone levels. In addition, there were no pathologic conditions
affecting other organs or pharmacologic treatments that could be responsible for
gynecomastia. Drug withdrawal started a progressive reduction of the lumps until
complete their disappearance. It is possible that gynecomastia was caused by
alterations of estrogen/androgen ratio because of a finasteride-induced decrease
in circulating dihydrotestosterone levels. In this article, the authors confirm
finasteride antiandrogenic activity and recommend a close follow-up of long-term
treatments with finasteride to find out other possible side effects.
7.)Incidence and severity of sexual adverse experiences in finasteride and placebo-treated
men with benign prostatic hyperplasia.
Urology. 2003 Mar;61(3):579-84.
Wessells H, Roy J, Bannow J, Grayhack J, Matsumoto AM, Tenover L, Herlihy R,
Fitch W, Labasky R, Auerbach S, Parra R, Rajfer J, Culbertson J, Lee M, Bach MA,
Waldstreicher J; PLESS Study Group.
University of Washington, Seattle, Washington, USA.
OBJECTIVES: To evaluate the incidence and resolution of sexual adverse
experiences (AEs) in men with benign prostatic hyperplasia treated with
finasteride 5 mg compared with placebo. METHODS: The Proscar Long-term Efficacy
and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled
trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45
to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates,
and no evidence of prostate cancer. Patients completed a questionnaire at
screening regarding their history of sexual dysfunction. During treatment,
spontaneously self-reported sexual AEs were recorded. RESULTS: At screening, 46%
of patients in each treatment group reported some history of sexual dysfunction.
During year 1 of the study, 15% of finasteride-treated patients and 7% of
placebo-treated patients had sexual AEs that were considered drug related by the
investigator (P <0.001). During years 2 to 4, no between-group difference was
noted in the incidence of new sexual AEs (7% in each group). The drug-related
sexual AE profile for finasteride was similar for men with or without a history
of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of
finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2%
of placebo patients discontinued the study because of sexual AEs. In men who
discontinued with a sexual AE, 50% and 41% experienced resolution of their
sexual AE after discontinuing finasteride or placebo therapy, respectively.
CONCLUSIONS: Compared with placebo, men treated with finasteride experienced new
drug-related sexual AEs with an increased incidence only during the first year
of therapy.
8.) Droga para la calvicie (Finasteride) reduce riesgo de cáncer pero aconsejan
cautela
Source: http://www.cnnenespanol.com/
24 de junio, 2003
(CNN) -- Un estudio difundido el martes indica que un medicamento para la
calvicie reduce en 25 por ciento las posibilidades de sufrir de cáncer de
próstata, pero también podría elevar el riesgo de sufrir formas más agresivas
del cáncer en algunos casos.
"La finasterida es la primera droga de la que se tiene conocimiento que puede
reducir el riesgo de cáncer de próstata", dijo el Ian Thompson, autor principal
del estudio patrocinado por el Instituto Nacional del Cáncer de Estados Unidos y
publicado en la edición online del New England Journal of Medicine.
"El medicamento funcionó en hombres que corrían alto riesgo de sufrir de cáncer
de próstata y también en la franja de bajo riesgo", añadió.
Pero, los investigadores expresaron cautela ante el uso del medicamento como
tratamiento preventivo y advirtieron que la finasterida parece aumentar las
posibilidades de que el cáncer sea más agresivo en los casos en los que se
contrae la enfermedad.
La droga se encuentra presente en bajas dosis en el medicamento contra la
calvicie Propecia y también se comercializa bajo el nombre Proscar para el
tratamiento de la próstata.
El Instituto Nacional del Cáncer en Estados Unidos calcula que si se realizara
un seguimiento de mil hombres de 63 años a lo largo de siete años, 60
contraerían cáncer de próstata, entre ellos 18 que sufrirían tumores agresivos
que se propagan rápidamente.
Si los mismos hombres tomaran finasterida durante siete años, sólo 45
contraerían el cáncer pero 22 presentarían tumores agresivos.
Calvicie y cautela
Pese a que el estudio representa un avance en el tratamiento del cáncer de
próstata los pacientes deben sopesar bien las ventajas y los riesgos que
conlleva, señaló el doctor Harmon J. Eyre, médico principal de la Sociedad del
Cáncer de Estados Unidos.
En cuanto a los hombres que utilizan la droga para promover el crecimiento del
cabello, el doctor John Wasson, director del Centro de Envejecimiento de la
Facultad de Medicina Dartmouth, señaló:
" Ciertamente yo no quisiera tomar un medicamento que potencialmente puede
promover un tipo agresivo de cáncer".
"Lo primero que hay que pensar sobre un medicamento o tratamiento es que no haga
daño. Si uno es un hombre joven debería tener cuidado con la finasterida",
añadió.
El especialista estima que los resultados del estudio podrían llevar a que la
Agencia de Alimentos y Drogas de Estados Unidos revise la información disponible
sobre la droga, producida por los laboratorios Merck y de venta bajo receta.
Ningún funcionario del organismo de salud se pronunció sobre el tema y el
intento de CNN de obtener declaraciones del laboratorio fue infructuoso.
9.) Proscar: five-year experience
Eur Urol. 1995;28(4):304-9.
Erratum in:
Eur Urol 1996;29(2):234.
Moore E, Bracken B, Bremner W, Geller J, Imperato-McGinley J, McConnell J, Roy
J, Tenover L, Vaughan D, Pappas F.
Merck Research Laboratories, Rahway, NJ 07065, USA.
We assessed the long-term safety and efficacy of finasteride, an orally active 5
alpha-reductase inhibitor, in 2 previously reported groups of patients with
symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by
magnetic resonance imaging, and the maximum urinary flow rate was assessed
noninvasively. Symptoms were scored utilizing a patient self-administered
symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic)
to 35 (severely symptomatic). After an initial double-blind period, the patients
in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5
mg finasteride for an additional 4 years, whereas patients in study 2 were
treated with 5 mg finasteride for the entire 5 years. A total of 190 patients
were randomized in the double-blind studies, 156 entered year 1 of the open
extension and 70 patients completed 5 years of finasteride therapy. In both
studies prostate volume was reduced from baseline by 30%, dihydrotestosterone
was reduced by 72%, and the maximum urinary flow rate improved by approximately
1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%.
Finasteride was well tolerated; approximately 10% of patients reported sexual
adverse experiences during the 5-year study period, which were considered drug
related by the investigators. The incidence in reporting sexual adverse
experiences did not increase with the increased duration of treatment: findings
consistent with previous reports. In summary treatment of BPH with finasteride
for 5 years inhibits the progression of the disease with an excellent safety
profile and represents a low-risk medical option for the treatment of
symptomatic BPH.
10.) Long-term (7 to 8-year) experience with finasteride in men with benign
prostatic hyperplasia.
Urology. 2002 Dec;60(6):1040-4.
Vaughan D, Imperato-McGinley J, McConnell J, Matsumoto AM, Bracken B, Roy J,
Sullivan M, Pappas F, Cook T, Daurio C, Meehan A, Stoner E, Waldstreicher J.
Cornell University Medical Center, New York, New York, USA.
OBJECTIVES: To evaluate the effects of finasteride, a specific type II 5-alpha-reductase
inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and
urinary flow during a 7 to 8-year period. METHODS: A total of 190 men with
symptomatic benign prostatic hyperplasia and enlarged prostates entered one of
two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued
taking open-label finasteride, and more than 70 patients completed 7 to 8 years
of treatment. The symptoms were scored using a patient self-administered
modified Boyarsky symptom questionnaire. Prostate volume was measured by
magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate
was assessed noninvasively. RESULTS: Treatment with finasteride for 7 to 8 years
led to sustained improvement in symptoms, reduction in prostate volume (28% from
baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases
in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were
also maintained. Long-term finasteride treatment was safe and generally well
tolerated. CONCLUSIONS: Long-term treatment with finasteride was well tolerated
and resulted in durable symptom relief and improvement in prostate volume and
urinary flow.
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DATA-MEDICOS/DERMAGIC-EXPRESS /JUNE JOURNAL 2.003/ DR. JOSE
LAPENTA R.
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