Goserelin

Molecular formula C59H94N,sOu Molecular weight 1269.4 CAS Registry No. 65807-02-5 

Mobile phase Gradient. A was 0.05% phosphoric acid containing 0.5% (NH4 2S04. B was MeCN. A B from 82 18 to 64 36 over 25 min, maintain at 64 36 for 2.5 min, return to initial conditions over 1 min, re-equilibrate for 6.5 min or isocratic 76 24 Flow rate 0.5 Detector UV 210 

Simultaneous buserelin, deslorelin, gonadorelin, leuprolide, nafarelin 

Corran, P.H. Sutcliffe, N. Identification of gonadorelin (LHRH) derivatives comparison of reversed-phase high-performance liquid chromatography and micellar electrokinetic chromatography. J.Chromatogr., 1993, 636, 87-94 

Mobile phase MeCN water triethylamine 10 89 1 adjusted to pH 6 with orthophosphoric acid 

---

Gonadotropin releasing hormone analogs (goserelin, buserelin, leuprorelin, triptorelin) inhibit gonadotropin release and thus lower testosterone or estrogen levels. They are used to treat breast cancer and prostate cancer. 

Goserelin (Zoladex), a hormonal antineoplastic drug used to treat breast cancer, is administered subcutaneously in an unusual way. The drag is contained in a dry pellet that is implanted in the soft tissue of the abdomen, where it is gradually absorbed during a period of 1 to 3 months. After a local anesthetic, such as lido-caine, is administered, a large needle (usually 16 gauge) is used to insert the pellet. 

LHRH Analogs Goserelin Leuprolide Triptorelin 3.6 mg SC every 28 days 7.5 mg IM every 28 days 3.75 mg IM every 28 days Hot flashes, amenorrhea, menopausal symptoms, injection site reactions... 

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer.19 Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens.19 There are no direct comparative trials of the currently available LHRH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore, the choice between the two usually is made based on cost and patient and physician preference for a dosing schedule. 

Combining an LHRH agonist with flutamide demonstrated response rates greater than 90% in previously untreated patient, and the median survival was 61 months in the combination arm and 41 months in the leuprolide-alone arm in patients with minimal disease.38 However, in a comparison of goserelin with goserelin and flutamide conducted in 589 patients with 10 years of follow-up, combined androgen blockade (CAB) showed no benefit over goserelin alone.39... 

Goserelin -LHRH agonist -endocrine effects -hot flashes -decreased libido -gynecomastia -impotence -nausea and vomiting (uncommon) -transient increase in bone pain... 

LHRH analogs Goserelin 3.6 mg SC every 28 days Hot flashes, amenorrhea, menopausal symptoms,... 

Ovarian ablation (oophorectomy) is considered by some to be the endocrine therapy of choice in premenopausal women and produces similar overall response rates as tamoxifen. Medical castration with an LHRH analog, goserelin, leuprolide, or triptorelin, is a reversible alternative to surgery. 

There are no comparative trials of LHRH agonists, so the choice is usually based on cost (Table 65-1) and on patient and physician preference. Leuprolide acetate is administered daily. Leuprolide depot and goserelin acetate implant can be administered monthly, or every 12 or 16 weeks. 

Hoitink, M. A., Hop, E., Beijnen, J. H., Bull, A., Kettenes-van den Bosch, J. J., and Underberg, W. J. M. (1997). Capillary zone electrophoresis mass spectrometry as a tool in the stability research of the luteinising hormone-releasing hormone analogue goserelin.. Chromatogr. A 776, 319—327. 

Dutta AS, Furr BJA, Hutchinson FG. The discovery and development of goserelin (Zoladex). Pharma Med 1993 7 9-28. 

---