Should goserelin (a luteinizing hormone-releasing hormone (LHRH) agonist) be administered every 2 weeks for the first 3 cycles?

Administration of Goserelin in the First 3 Cycles

For the first 3 cycles, goserelin should NOT be given every 2 weeks but should follow the standard dosing schedule of 3.6 mg subcutaneously every 4 weeks (28 days) or 10.8 mg every 12 weeks.

Standard Dosing Schedule for Goserelin

Goserelin is a luteinizing hormone-releasing hormone (LHRH) agonist that is administered as a subcutaneous depot injection. The FDA-approved and guideline-recommended dosing is:

• 3.6 mg subcutaneously every 28 days (4 weeks) 1
• 10.8 mg subcutaneously every 3 months (12 weeks) 1

Pharmacological Rationale

Goserelin works through a specific mechanism that requires consistent dosing:

• Initial administration causes a transient increase in LH and FSH levels, followed by downregulation of pituitary receptors 2
• This leads to suppression of testosterone or estradiol to castrate or menopausal levels within 3-4 weeks 3
• The depot formulation is designed to release the drug continuously over the 28-day period 4
• Altering this schedule to every 2 weeks would disrupt the pharmacokinetic profile and potentially affect efficacy

Clinical Applications

For Prostate Cancer

• Standard dosing of 3.6 mg every 28 days or 10.8 mg every 12 weeks is recommended 3
• An antiandrogen should be given for 3-4 weeks when starting goserelin to counteract testosterone flare 3

For Breast Cancer

• In premenopausal women with hormone-responsive breast cancer, goserelin is administered at 3.6 mg every 28 days 3
• The NCCN guidelines specifically recommend goserelin 3.6 mg SC every 4 weeks or 10.8 mg SC every 12 weeks 3

Management of Initial Flare Phenomenon

The "flare phenomenon" occurs during the first 1-2 weeks of treatment due to the initial rise in hormone levels:

• In prostate cancer, this can be managed by adding an antiandrogen during the first 3-4 weeks 3
• In breast cancer, when used with aromatase inhibitors, goserelin should be started alone for at least 1-2 cycles until estradiol levels reach postmenopausal range 3

Monitoring Requirements

• For breast cancer patients: Monitor estradiol and FSH/LH levels prior to the next dose of goserelin, particularly in women under 45 3
• For prostate cancer patients: Monitor PSA levels and clinical symptoms 3

Potential Pitfalls

• Administering goserelin every 2 weeks could potentially:
  • Disrupt the established pharmacokinetic profile
  • Lead to inconsistent hormone suppression
  • Increase the risk of adverse effects
  • Deviate from evidence-based practice

Conclusion

The evidence consistently supports administering goserelin at standard intervals of 3.6 mg every 28 days or 10.8 mg every 12 weeks, even during the initial treatment period. There is no evidence supporting a 2-week dosing schedule for the first 3 cycles in either prostate or breast cancer treatment.