Elsevier

The Lancet

Volume 323, Issue 8383, 28 April 1984, Pages 971-972
The Lancet

Letters to the Editor
DISEASE FLARE INDUCED BY D-Trp6-LHRH ANALOGUE IN PATIENTS WITH METASTATIC PROSTATIC CANCER

https://doi.org/10.1016/S0140-6736(84)92435-8Get rights and content

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    Although GnRH receptor agonists are some of the more popular drugs used in the treatment of androgen-sensitive prostate cancer,37,38 this class of drugs may not be suitable for some patients. Accordingly, GnRH receptor agonists initially result in a stimulatory effect on pituitary LH release, which not only results in a delayed onset of action relative to long-acting GnRH receptor antagonists, but also may result in a flare up of the disease.39 Accordingly, in male rats, whereas castration levels of testosterone are achieved within 28 days of treatment with leuprolide, rats treated with degarelix (1 mg/kg) exhibited castration levels of testosterone within 2 days.40

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    In the early 1980s, the phenomenon of disease flare was reported within case reports. Kahan et al. [6] published a report on a patient with newly diagnosed advanced prostate cancer in whom disease flare induced by LHRH agonist treatment would have been responsible for excruciating pain requiring major narcotic analgesia, a rapidly progressive delirious state, and finally death. In a second case, a sudden paraplegia due to spinal cord compression even set up 5 to 6 hours after the injection.

  • Prospective evaluation of testosterone fluctuations during a transition of therapy from degarelix to leuprolide in patients on androgen deprivation therapy

    2014, Urology
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    They reported a 10% incidence of bone pain progression during the first week of GnRH therapy. Even more concerning are reports, however scarce, of deaths occurring during GnRH induction presumed secondary to disease flare and possible spinal cord compression.11,12 Thompson et al8 reviewed 765 cases in 9 series and found that 10.9% of patients experienced a clinical flare, including 15 who died during the testosterone surge.

  • Degarelix: A Novel Gonadotropin-Releasing Hormone (GnRH) Receptor Blocker-Results from a 1-yr, Multicentre, Randomised, Phase 2 Dosage-Finding Study in the Treatment of Prostate Cancer

    2008, European Urology
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    However, the GnRH agonists initially activate the receptors, resulting in a surge in LH and testosterone as well as a delayed reduction in prostate-specific antigen (PSA) levels for 2–3 wk before androgen deprivation is achieved [7,8]. The surge can delay the therapeutic benefit and may exacerbate the clinical status by provoking or exacerbating symptoms such as urinary retention, bone pain, and paraplegia due to spinal-cord compression by spinal metastases [9]. Patients most at risk for this clinical flare are those with high-volume, symptomatic, metastatic disease [10].

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