Phase II Study of Goserelin for Ovarian Protection in Premenopausal Patients Receiving Cyclophosphamide Containing Chemotherapy: Menstruation Outcome
Phase: PHASE2
Conditions: Ovarian Failure
Sponsor: Assiut University

 
 
 
 
 
ASSIUT UNIVERSITY HOSPITAL, CLINICAL ONCOLOGY 
DEPARTMENT 
Phase II study of Goserelin for ovarian protection in 
premenopausal patients receiving cyclophosphamide 
containing chemotherapy: menstruation outcome. 
By : 
 
Ahmed Mohamed Ashraf Saadeldin Abbas 
3/17/2018 
 

Phase II study of Goserelin for ovarian protection in 
premenopausal patients receiving cyclophosphamide 
containing chemotherapy: menstruation outcome.
 
 
Introduction
 
The use of adjuvant chemotherapy in younger women 
with early breast cancer (EBC) has substantially 
improved the long-term outcome [1]. However, this 
benefit is associated with long-term toxic effects which 
are becoming more important as prognosis improves. 
These include premature menopause and infertility in 
young pre-menopausal women. The incidence of 
premature menopause depends on the type and intensity 
of chemotherapy and the patient’s age. In women <35 
years old, the long-term (3 years after diagnosis) 
incidence of amenorrhea is similar to women who have 
not received chemotherapy, at ∼ 10%, but this increases 
to 50% in women between 35 and 40 years old, and can 
be up to 85% in women >40 years [2]. Premature ovarian 
failure has major consequences including sexual 
dysfunction and infertility, and the latter may be of great 
concern to younger patients with breast cancer and has a 
bearing in influencing treatment decisions in almost 30% 
of cases [3]. 
Currently, there is no standard treatment for preventing 
chemotherapy-induced ovarian failure. Previous studies 
have suggested that temporary ovarian suppression with 
a gonadotropin-releasing hormone (GnRH) analogue 
may preserve ovarian function both in humans and 
animal models [4–9]. Clinical data are conflicting. For 
example, a recent Italian multi-center phase III study 

Prevention of Menopause-Induced by Chemotherapy: A 
Study in Early Breast Cancer Patients-Gruppo Italiano 
Mamella 6 (PROMISE-GIM6) reported that the use of 
GnRH analogue, triptorelin during chemotherapy in pre-
menopausal patients with EBC, reduced the occurrence 
of chemotherapy-induced early menopause with four 
pregnancies after a 26-month follow-up [one in the 
chemotherapy alone arm and three in the triptorelin with 
chemotherapy arm] [10]. In contrast, another trial 
suggested that the use of goserelin concurrently with 
neoadjuvant chemotherapy did not significantly reduce 
incidence of amenorrhea 6 months after the end of 
chemotherapy compared with those receiving 
chemotherapy alone and only two pregnancies were 
recorded [one in each arm] with a follow-up of 2 years 
[11]. 
 
 
 
 
 
 
 
 
 
 

Study objectives 
Determination of the role of Goserelin for ovarian 
protection in premenopausal patients receiving 
cyclophosphamide containing chemotherapy: 
menstruation outcome. 
Patients and methods 
Eligibility criteria: 
-Premenopausal cancer patients who will recieve 
Cyclophosphamide-containing chemotherapy. 
-ECOG performance status (PS) ≤ 2. 
-Informed consent will be taken from eligible patients 
before enrollment. 
Exclusion Criteria: 
Postmenopausal cancer patients 
Cancer patients who will receive non Cyclophosphamide 
containing chemotherapy 
Study design: 
This study is a randomized prospective phase II study 
Study type: interventional 
Study design: 
Allocation: randomized 
Endpoint classification: efficacy study 

Primary endpoint: compare rate of ovarian failure at 1 
year between the two treatment groups with ovarian 
failure defined as the absence of menses in the preceding 
6 months and levels of FSH in the postmenopausal range. 
Secondary endpoint: median time to recovery of menses 
from the final dose of goserelin. 
Official title: Phase II study of Goserelin for ovarian 
protection in premenopausal patients receiving 
cyclophosphamide containing chemotherapy: 
menstruation outcome.
 
 
Pretreatment assessment: 
Eligible patients will be subjected to the following: 
-History and physical examination especially menstrual 
history 
-baseline hormonal profile (FSH, LH, E2) 
 
 
Treatment protocol: 
In this phase II trial, patients will be randomly assigned, 
in a 1:1 ratio, to standard adjuvant or neoadjuvant 
chemotherapy with the GnRH agonist goserelin 
(goserelin group) or to chemotherapy without goserelin 
(chemotherapy alone group). 

For Patients randomly assigned to the goserelin group, 
goserelin at a dose of 3.6 mg will be administered 
subcutaneously every 4 weeks beginning 1 week before 
the initial chemotherapy dose and will be continued to 
within 2 weeks before or after the final chemotherapy 
dose. 
Follow up: All patients will be followed for at least 1 
year clinically monthly and by laboratory assessment by 
hormonal profile (FSH, LH, E2) every 6 months. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
References
 
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