Prevention of chemotherapy-induced menopause by temporary ovarian suppression with goserelin in young, early breast cancer patients

Del Mastro, L.
Catzeddu, T.
Boni, L.
Bell, C.
Sertoli, M. R.
Bighin, C.
Clavarezza, M.
Testa, D.
Venturini, M.

¹Oncologia Medica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
²Sperimentazioni Cliniche Controllate, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
³Stanford University Cancer Center, Stanford, California
⁴Università degli Studi, Genova, Italy
⁵Laboratorio Endocrinologia Azienda Ospedaliera S. Martino, Genova, Italy

Received 21 July 2005; revised 31 August 2005; accepted 31 August 2005

^*Correspondence to: Dr L. Del Mastro, Department Medical Oncology, National Cancer Research Institute, L.go R. Benzi 10, 16132 Genoa, Italy. Tel: +39-010-5600666; Fax: +39-010-5600850; E-mail: [email protected]

Annals of Oncology 17(1):p 74-78, January 2006.

Background

Standard methods to prevent chemotherapy-induced early menopause in young, breast cancer patients are unavailable to date. Preclinical data has suggested that luteinising hormone-releasing hormone (LH-RH) analogs given during treatment can decrease the gonado-toxicity induced by chemotherapy. This phase II study aimed to assess the activity of such a method in young, breast cancer patients undergoing adjuvant chemotherapy.

Patients and methods

Premenopausal patients received the LH-RH analog goserelin 3.6 mg every 4 weeks before and during chemotherapy. According to two-stage optimal phase II Simon design, treatment was considered clinically interesting if it was able to prevent menopause in 19 out of 29 patients of the study population. The resumption of ovarian function was defined by a resumption of menstrual activity or by a follicle-stimulating hormone (FSH) value ≤40 IU/l within 12 months after the last cycle of chemotherapy.

Results

Thirty patients were enrolled and 29 were evaluable. Median age was 38 years (range 29–47). All but one patient received CEF regimen (cyclophosphamide, epirubicin, 5-fluorouracil). Resumption of menstrual activity was observed in 21 patients (72%; 95% CI 52% to 87%) and a FSH value ≤40 IU/l in 24 patients (83%; 95% CI 63% to 93%). Menses resumption was observed in 16 out of 17 patients (94%) with age <40 years and in five out of 12 patients (42%) with age ≥40 years.

Conclusion

Goserelin given before and during chemotherapy may prevent premature menopause in the majority of patients. The different success rate by age, however, indicates the need of a prospective evidence of the efficacy of such a strategy.