None listed
Conditions
Brief summary
Non-Hodgkin’s lymphoma (NHL) is one of the most common cancers diagnosed in young women, with approximately 105 women under 40 years diagnosed in Australia annually (2005 data), most of whom will have aggressive histology. In aggressive NHL, standard treatment is 6 cycles of R-CHOP-q21. Recently, an accelerated protocol (R-CHOP-q14) has been widely adopted. This regimen has been demonstrated to produce sustained remissions in at least 75% of women aged <40 (J Connors 2010, personal communication). The risk of early ovarian failure with regimens of variable intensity used in NHL (including CHOP) is estimated to be 10-40% (Avishay et al, 2006; Dolmans et al, 2005). Currently, however, there are no specific data available about the short or long-term effects of R-CHOPq14 on fertility, (Pfreundschuh 2008, personal communication) but the more intensive regimen may be expected to induce a higher incidence of ovarian damage than the q21 protocol. It is important, therefore, that the impact of this chemotherapy on fertility be evaluated in this patient population of child-bearing age with a high survival rate (Nicosia et al, 1985), as interventions aiming to protect fertility are worthy of study. There is increasing evidence that fertility protection may be achieved with a GnRH agonist during chemotherapy. Two recent meta-analyses, despite showing benefit from use of GnRH agonists (p<0.05 in one analysis), concluded that because of the lack of randomization in various studies, there was not yet enough evidence to definitively resolve the issue (Beck-Fruchter et al, 2008; Blumenfeld et al, 2008). More recently, results of a randomized controlled trial in patients with breast cancer found a statistically significant reduction in ovarian failure in patients who received concomitant GnRH agonist (Badawy et al, 2009). The lack of data regarding ovarian failure risk with treatment of NHL, and the absence of specific previous trials assessing ovarian protection in this context, both provide the rationale for further evaluation of a GnRH agonist in a rigorous, Australia-wide, clinical trial setting. This randomized, controlled study aims to identify: (1) the underlying risk of temporary and more permanent ovarian failure for patients receiving an accelerated protocol, R-CHOP –q14. (2) whether there is any ovarian protective effect from concurrent administration of a GnRH agonist.
Interventions
- Zoladex 3.6mg will be administered subcutaneously in the anterior abdominal wall. Ideally this will first occur up to 10-14 days prior to commencement of treatment with chemotherapy; however patients will be accepted onto the trial providing the first dose of Zoladex is given no later than one week following the start of the first course of chemotherapy
- Zoladex will be given every 28-32 days as required to cover the duration of the chemotherapy (expected four injections).
The patients wil
- Zoladex 3.6mg will be administered subcutaneously in the anterior abdominal wall. Ideally this will first occur up to 10-14 days prior to commencement of treatment with chemotherapy; however patients will be accepted onto the trial providing the first dose of Zoladex is given no later than one week following the start of the first course of chemotherapy - Zoladex will be given every 28-32 days as required to cover the duration of the chemotherapy (expected four injections). The patients will also receive the "progesterone-only" pill and calcium supplements. The progesterone-only pill - 0.35mg of norethisterone, daily from day 1 of chemotherapy to the end of chemotherapy. This is the only contraception allowed during chemotherapy however it maybe continued post chemotherapy if so desired. Calcium supplements - 600mg once daily from day 1 of chemotherapy to the end of chemotherapy.
Sponsors
Melbourne in vitro fertilization (IVF)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
13 Years to 38 Years
Healthy volunteers
No
Inclusion criteria
- women anticipated to receive 6 cycles of R-CHOP-14 with curative intent for Non-Hodgkin's Lymphoma (NHL) - resident in Australia for the duration of trial participation - a minimum of 12 months post-menarche and be less than or equal to 38 years at the start of treatment - premenopausal state, as demonstrated by greater than and equal to 3 spontaneous menstrual cycles in the last 6 months or by non-menopausal levels of FSH or oestradiol at baseline - ability to administer the first dose of Zoladex no later than 1 week after commencing chemotherapy - consent to utilizing a progesterone-only contraceptive during their chemotherapy and also barrier contraception for 8 weeks prior to each follow up blood test - ability to give informed consent. For patients under 18 years parental consent must be given, with patient assent where appropriate
Exclusion criteria
- known contraindication to the use of a GnRH analogue (e.g. pregnancy or hypersensitivity) or a progesterone-only contraceptive - anticipated requirement for pelvic irradiation as part of therapy - radiological evidence of ovarian involvement with NHL - prior cytotoxic chemotherapy for this or any other diagnosis - contraindication to use of a progesterone-only contraceptive pill (e.g. previous history of thromboembolic disease)
Outcome results
None listed