Is the flare phenomenon clinically significant?

Authors
Citation
Gj. Bubley, Is the flare phenomenon clinically significant?, UROLOGY, 58(2A), 2001, pp. 5-9
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology
Journal title
UROLOGY
ISSN journal
0090-4295 → ACNP
Volume
58
Issue
2A
Year of publication
2001
Supplement
S
Pages
5 - 9
Database
ISI
SICI code
0090-4295(200108)58:2A<5:ITFPCS>2.0.ZU;2-I
Abstract
Objectives: The existing luteinizing hormone-releasing hormone (LHRH) analo gs have been the preferred method of inducing androgen deprivation for pros tate cancer for over a decade. These agents are well known to cause a surge in serum testosterone levels during the first week of therapy. However, th ere are wide discrepancies in reports of the frequency and severity of acut e clinical progression or clinical flare that might result from the testost erone surge. Also, there is not a clear consensus as to whether antiandroge ns should be routinely given to all patients during the first month of LHRH therapy to prevent flare responses. Methods: Clinical trials involving LHRH analog therapy for prostate cancer were reviewed, and the frequency of clinical flare responses noted. Particu lar attention was given to the kinds of clinical problems associated with t he flare response. The use of LHRH analog therapy in treatment of patients with prostate cancer for indications other than overt metastatic disease is discussed, because this is becoming a much more common use of these agents . This article analyzes 2 placebo-controlled, double-blind trials testing t he effectiveness of existing antiandrogens in ameliorating flare responses. Results: The use of LHRH analogs for patients with stage D2 disease can be associated with clinical flare in approximately 10% of D2 patients. In addi tion to bone pain, cord compression, and bladder outlet obstruction, anothe r potentially severe side effect is cardiovascular risk arising presumably from hypercoagulability associated with a rapid increase in tumor burden. I n clinical series involving D2 patients, the frequency of clinical flare gr eatly varies, probably because of the level of scrutiny of the investigator and/or the prostate-cancer tumor burden present at the initiation of thera py. Concomitant antiandrogen therapy reduces, but does not totally eliminat e, the flare responses in patients at high risk for flare. Treating prostat e cancer in the DO stage or in the neoadjuvant setting will result in bioch emical evidence of testosterone surge, but these patients are at very littl e risk for clinical flare responses. Conclusions: There is a wide variation in the reported frequency of clinica l flare responses from LHRH analogs during the initial treatment of patient s with stage D2 disease. The risk-to-benefit ratio, especially in patients with symptomatic bone metastasis, would dictate routine use of antiandrogen therapy for the first month of LHRH analog treatment. For patients at risk for cord compression, other means of ablating testosterone might be consid ered, such as ketoconazole, orchiectomy, or LHRH antagonists. Clinical flar e responses, as opposed to biochemical flare responses, are very rare durin g LHRH analog therapy for stage DO disease and/or in the setting of neoadju vant hormonal therapy.