In a secondary analysis of the UK phase III RATHL trial reported in The Lancet Oncology, Anderson et al found that ovarian function recovery was affected by age and type of response-adapted therapy in women receiving treatment for advanced Hodgkin lymphoma.
The analysis included 67 eligible patients. All had received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or AVD followed by interim positron-emission tomography/computed tomography. Patients with negative scans continued ABVD or AVD for four more cycles (n = 57; 24 ABVD, 33 AVD), whereas those with positive scans had treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (n = 10; 4 BEACOPP-14, 6 escalated BEACOPP) for four cycles. Ovarian function was assessed before treatment, during chemotherapy, and then annually for 3 years using serum anti-Müllerian hormone and follicle-stimulating hormone.
Ovarian Function Outcomes
Anti-Müllerian hormone concentrations were found to decrease during both chemotherapy regimens. At 1 year after chemotherapy, anti-Müllerian hormone concentrations recovered to a median of 10.5 pmol/L in the ABVD/AVD group, with little recovery observed in the BEACOPP group (median = 0.11 pmol/L). Among patients in the ABVD/AVD group, complete anti-Müllerian hormone recovery to 127% of baseline was observed in those aged < 35 years, whereas recovery to 37% was observed in those aged ≥ 35 years (P < .0001).
Follicle-stimulating hormone recovery to < 25 IU/L occurred in 95% of women aged < 35 years in the ABVD/AVD group by 2 years compared with 79% of those aged ≥ 35 years (hazard ratio = 0.49, P < .0001); proportions were similar at 3 years (98% vs 93%). Recovery among patients treated with BEACOPP was 33% after 1 year and 69% after 2 years.
The investigators concluded, “Reduced recovery of ovarian function observed in women older than 35 years treated with ABVD or AVD compared with younger women indicates that treatment could reduce their reproductive lifespan and supports discussion of fertility preservation before treatment. Women treated with BEACOPP should be informed of its potential high gonadotoxicity. These findings warrant further investigation in large, prospective studies with fertility and reproductive lifespan as outcomes.”
The study was funded by the Medical Research Foundation and Cancer Research UK.
Richard A. Anderson, MD, of the MRC Centre for Reproductive Health, Queen’s Medical Research Institute, University of Edinburgh, is the corresponding author for The Lancet Oncology article.
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