Damage to the ovaries is likely in women with Hodgkin’s lymphoma who are 35 years old or older and given standard chemotherapy, and in those at any age treated with BEACOPP chemotherapy, a secondary analysis of a Phase 3 study shows.
The study, “Determinants of ovarian function after response-adapted therapy in patients with advanced Hodgkin’s lymphoma (RATHL): a secondary analysis of a randomised phase 3 trial,” was published in the journal The Lancet Oncology.
Potential chemotherapy-induced ovarian insufficiency greatly concerns premenopausal women with cancer, especially those with Hodgkin’s lymphoma, who are often diagnosed at a younger age (median of 35 years).
The current standard treatment for Hodgkin’s lymphoma is a ABVD chemotherapy regimen – Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine – which is associated with less ovarian damage than previous treatments.
In patients with advanced disease or at higher risk of relapse, some clinicians support the use of BEACOPP chemotherapy (a combination of bleomycin, etoposide, Adriamycin, cyclophosphamide, oncovin, procarbazine, and prednisolone). However, this treatment is linked to higher toxicity in the ovaries.
Researchers in Edinburgh and London evaluated the impact of different chemotherapy regimens – ABVD or AVD (Adriamycin, vinblastine, and dacarbazine), and escalated-dose BEACOPP (given every 21 days), or time-intensive BEACOPP-14 (given every 14 days) — on ovarian function in adult women with Hodgkin’s lymphoma.
They recruited women younger than age 45 at the time of diagnosis among participants of the randomized RATHL Phase 3 trial (NCT00678327) – which used positron emission tomography-computed tomography (PET/CT) scanning to guide response-adapted chemotherapy in patients with advanced Hodgkin’s lymphoma.
Ovarian function was assessed during and up to three years after chemotherapy through blood levels of antimüllerian — a hormone secreted by cells in developing egg sacs, which is used to estimate the remaining egg supply – and follicle-stimulating hormone, which regulates ovarian function and responds to the normal ovarian production of the female hormones estrogen and progesterone.
Sixty-seven women – 33 (49.3%) treated with AVD, 24 (35.8%) with ABVD, six (9%) with escalated BEACOPP, and four (6%) with BEACOPP-14 – were monitored for antimüllerian hormone. Another 321 women – 142 (44.2%) treated with ABVD, 140 (43.6%) with AVD, 20 (6.2%) with escalated BEACOPP, and 19 (5.9%) with BEACOPP-14 – were assessed for follicle-stimulating hormone.
Results showed that blood levels of antimüllerian hormone were substantially reduced during ABVD/AVD and BEACOPP chemotherapy regimens. A recovery to normal levels at one year after therapy was seen in those given ABVD/AVD, but BEACOPP-treated patients showed a poor recovery in antimüllerian hormone levels.
Researchers also found that recovery after ABVD/AVD therapy was dependent on age, as those diagnosed with Hodgkin’s lymphoma before age 35 showed a complete recovery, while an incomplete one was seen in women diagnosed at 35 or later in life.
Levels of antimüllerian hormone were not found to be a good predictor of short-term fertility — some pregnancies were observed in women with very low levels of this hormone – indicating a still unmet need for a good predictor of infertility in cancer survivors.
The levels of follicle-stimulating hormone showed similar but inverted trends, with increased hormone levels during all chemotherapy regimens, and a decrease to normal levels at one year after treatment only in patients given ABVD/AVD chemotherapy. This recovery was also slower in women 35 or older.
These findings “highlight the importance of discussing access to these options in women older than 35 years, irrespective of chemotherapy type, and among candidates to the BEACOPP regimen, irrespective of their age,” Matteo Lambertini and Isabelle Demeestere, two experts in cancer and fertilization, wrote in a comment published in the same journal issue.
The researchers noted that additional and larger studies are necessary to confirm and clarify their results.