ABSTRACT
Leuprolide (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered to 26 premenopausal women with metastatic breast cancer. Of 25 evaluable patients, 11 (44%) had a partial response with a median duration of 39 weeks and five (20%) remained stable. Six patients showed early rapid progression of their disease. Toxicity was mild and included hot flashes, nausea, vomiting, and headache. Leuprolide induced amenorrhea in all patients who received treatment for ten weeks or longer. We conclude that this GnRH analogue provides a safe and effective means of producing medical castration in premenopausal patients with metastatic breast carcinoma.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Gonadotropin-Releasing Hormone/analogs & derivatives , Adult , Antineoplastic Agents/adverse effects , Breast Neoplasms/blood , Combined Modality Therapy , Drug Evaluation , Female , Gonadotropin-Releasing Hormone/adverse effects , Gonadotropin-Releasing Hormone/therapeutic use , Hormones/blood , Humans , Leuprolide , Mastectomy , Menstruation , Middle Aged , Neoplasm Metastasis , Ovary/drug effects , Receptors, Estrogen/analysisABSTRACT
Administration of the superagonist analog of GnRH, D-Leu6-GnRH proethylamide, profoundly reduced plasma LH, FSH, testosterone, and dihydrotestosterone levels when given for 6-11 weeks to adult men with prostatic carcinoma. Since patients with prostatic carcinoma can be expected to receive this analog for as long as 3-4 yr, we questioned whether the same degree of reduction could be maintained during chronic administration. In 22 men who had received D-Leu6-GnRH proethylamide for at least 1 yr, LH and testosterone remained at the initial low levels. Plasma dihydrotestosterone concentrations, on the other hand, gradually fell further with long term administration. FSH levels reached a nadir of 5.7 +/- 0.94 (+/- SEM) mIU/ml at 10-11 weeks. Unexpectedly, the plasma levels of this gonadotropin then gradually increased, and between 25 and 97 weeks were approximately 10-15 mIU/ml. This pattern occurred identically in patients receiving either 1 or 10 mg D-Leu6-GnRH proethylamide daily. These data indicate persistent suppression of LH and androgen levels during prolonged therapy and suggest that D-Leu6-GnRH-induced "medical castration" can be maintained with chronic administration.
Subject(s)
Gonadotropin-Releasing Hormone/analogs & derivatives , Prostatic Neoplasms/drug therapy , Aged , Dihydrotestosterone/blood , Follicle Stimulating Hormone/blood , Gonadotropin-Releasing Hormone/therapeutic use , Humans , Leuprolide , Luteinizing Hormone/blood , Male , Middle Aged , Prostatic Neoplasms/blood , Testosterone/blood , Time FactorsABSTRACT
Leuprolide is a new, potent analogue of gonadotropin-releasing hormone which, after an initial transient stimulation, causes a profound suppression of serum gonadotropins and testosterone. One hundred eighteen patients with advanced carcinoma of the prostate have undergone treatment with leuprolide in a multi-institutional trial. Minimal evidence of objective response was seen in patients who had failed prior endocrine therapy with orchiectomy or estrogens. In patients without previous hormonal treatment, leuprolide induced an objective disease response (72%) comparable to alternative primary endocrine therapy. Considering the lack of significant side effects seen with long-term GnRH agonists, compounds such as leuprolide may prove to be the preferred initial endocrine therapy for selected patients with metastatic carcinoma of the prostate.