Do gonadotrophin-releasing hormone (GnRH) agonists protect ovarian function in patients with Non-Hodgkin’s Lymphoma?

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.