UNIÃO DAS INSTITUIÇÕES DE SERVIÇO, ENSINO E PESQUISA LTDA - UNISEPE
CENTRO UNIVERSITÁRIO AMPARENSE - UNIFIA
Rod. “João Beira” – SP 95 - KM 46,5 – Bairro Modelo – Caixa Postal 118 – CEP: 13905-529 Amparo - SP
(19) 3907-9870 – e-mail: [email protected] – site: www.unifia.edu.br
ORCHIECTOMY VERSUS FLUTAMIDE
METASTATIC PROSTATE CANCER
IN
THE
TREATMENT
FOR
João Victor Fornari1; Daniele Rodrigues 2; Renato Nogueira Ferraz2 ; Maria Jose
Leonardo2; Daniela Angelo2; Israel Silva2; Anderson Bernabé2
1. Department of Biotechnology of the Universidade Nove de Julho –UNINOVE São Paulo, SP, Brazil
2. Departament of the Healt of the Universidade Nove de Julho – UNINOVE São Paulo, SP, Brazil
Introduction
Andenocarcinoma of the prostate is the most commonly diagnosed malignant
neoplasm in the United States of America.
1
Currently, there is no curative
treatment for patients with metastatic prostate cancer, who have a progressive
and eventually fatal clinical course. The median survival of cohorts of patients
with metastatic disease who have entered large-scale, prospective, randomized
trials during the past three decades has been relatively stable (range, 24 to 36
months).2 Deprivation has substantial palliative effects, but virtually in all
patients the tumor eventually progresses to an androgen-insensitive state in
which no treatment can prolong survival.3 Suppression of androgens of
testicular origin is the focus of androgen-deprivation treatment. This can be
accomplished by surgical castration or by medical suppression of testicular
function with synthetic analogues of gonadotropin-releasing hormone.2
However, after ablation of the tests by either means, the incorporation of
androgens into the cell nucleus continues, as a result of undiminished
production of androgens by the adrenal glands.3,4 The effects of these
androgens can be counteracted by adding an antiandrogen drug such as
flutamide to testicular removal. This form of combined androgen blockade
enhances antitumor effects and reduces the size of normal prostate glands and
seminal vesicles in animal models.4 Since the early 1980s, numerous
randomized clinical trials have evaluated the efficacy of combined androgen
blockade.2 Three large trials, including our previous trial, suggested that
combined androgen blockade conferred an important survival advantage.3
Methods
UNIÃO DAS INSTITUIÇÕES DE SERVIÇO, ENSINO E PESQUISA LTDA - UNISEPE
CENTRO UNIVERSITÁRIO AMPARENSE - UNIFIA
Rod. “João Beira” – SP 95 - KM 46,5 – Bairro Modelo – Caixa Postal 118 – CEP: 13905-529 Amparo - SP
(19) 3907-9870 – e-mail: [email protected] – site: www.unifia.edu.br
A systematic review was carried out in the MEDLINE database using the
following search strategy: (orchiectomy OR flutamide) AND metastatic prostate
cancer. The filter "Therapy/Narrow" was used through the Clinical Queries
interface. The authors analyzed the studies independently by title and the
summary of each recovered articles and selected those that met the inclusion
criteria: randomized clinical assay comparing the use of orchiectomy
with
flutamide drug that had been written in Portuguese, English or Spanish. After
this initial selection process, the authors read the full text of the eligible articles
and evaluated them critically. Only studies with a score > 3 according to the
criteria established by Jadad et al.
5
were included in the data analysis. To
evaluate effectiveness, we used the differences in mean time until crisis
resolution between the groups and the decrease in the mean pain score
according to the Visual Analog Scale (VAS). The measure used was the
absolute risk reduction (ARR) with the corresponding 95% confidence interval
(95% CI) and the number necessary to treat (NNT). The t-test was used to
analyze the continuous variables (for difference of means), with the OpenEpi
online tool and the Chi-square test was used to analyze dichotomous variables.
Results
The literature review was finished on November 10, 2011. A total of 04 articles
was found, of which only three met the inclusion criteria. After careful reading
and analysis of these three eligible articles, one was excluded for having losses
to follow-up > 20%. The only eligible article selected were the study by
Eisenberger et al.1, Boccon-Gibod et al.2 and Labrie et al.4 which had a score of
4 according to Jadad et al.5. The data of that study demonstrated there was no
significant difference in resolution time of vaso-occlusive crisis between the two
groups. The study p-value for the differences in medians was 0.87. The study
did not disclose the data on the time difference regarding crisis resolution as
means and standard deviations, whereas these data are usually expressed, but
as medians with 95% CI, of which upper and lower limits were not equidistant
from the median. Therefore, the authors calculated the one-sided p value in two
different ways: using the upper limits and the lower limits of the 95% CI. The
values obtained were 0.70 and 0.40, respectively.
UNIÃO DAS INSTITUIÇÕES DE SERVIÇO, ENSINO E PESQUISA LTDA - UNISEPE
CENTRO UNIVERSITÁRIO AMPARENSE - UNIFIA
Rod. “João Beira” – SP 95 - KM 46,5 – Bairro Modelo – Caixa Postal 118 – CEP: 13905-529 Amparo - SP
(19) 3907-9870 – e-mail: [email protected] – site: www.unifia.edu.br
Evidence synthesis
The use of Flutamide for the treatment of orchiectomy does not demonstrate
any significant differences regarding benefits or damages, when compared to
the conventional treatment.
References
1. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG,
Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ,
Lowe BA. N Bilateral orchiectomy with or without flutamide for metastatic
prostate cancer. Engl J Med. 1998 Oct 8;339(15):1036-42.
2. Boccon-Gibod L, Fournier G, Bottet P, Marechal JM, Guiter J, Rischman P,
Hubert J, Soret JY, Mangin P, Mallo C, Fraysse CE. Flutamide versus
orchidectomy in the treatment of metastatic prostate carcinoma. Eur Urol.
1997;32(4):391-5;
3. Rana A, Habib FK, Halliday P, Ross M, Wild R, Elton RA, Chisholm GD. case
for synchronous reduction of testicular androgen, adrenal androgen and
prolactin for the treatment of advanced carcinoma of the prostate.Eur J Cancer.
1995 Jun;31A(6):871-5.
4. Labrie F, Dupont A, Giguere M, Borsanyi JP, Belanger A, Lacourciere Y,
Emond J, Monfette G. Advantages of the combination therapy in previously
untreated and treated patients with advanced prostate cancer. J Steroid
Biochem. 1986 Nov;25(5B):877-83.
5. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et
al. Assessing the quality of reports of randomized clinical trials: is blinding
necessary? Control Clin Trials 1996;17:1-12.