Age is an important determinant of ovarian function recovery after chemotherapy for advanced Hodgkin's lymphoma, regardless of which regimen is used, according to new research that surprised investigators.

In a secondary analysis of the Risk Adopted Therapy in Lymphoma (RATHL) trial, recovery of ovarian function was reduced in women older than 35 years even when they were treated with regimens considered to have less gonadotoxicity.

The analysis also showed that the less toxic regimens had a very little impact on a woman's ability to conceive, as long as she was younger than 35 years. The study was published in the October issue of The Lancet Oncology. The current regimen of choice for many patients with Hodgkin's lymphoma is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

If the response to ABVD is inadequate, then treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone (BEACOPP) is warranted. However, female gonadal toxicity is high with BEACOPP, resulting in amenorrhea in about 95% of women older than 30 years.

"The main finding we had was the impact of age on the recovery of ovarian function after what we thought was relatively nonovarian toxic chemotherapy in the women who received ABVD," lead author Richard A. Anderson, MD, MRC Center for Reproductive Health at the University of Edinburgh, Scotland, told. "This finding was unexpected."

"People have known for a while that BEACOPP is more toxic than ABVD on ovarian function. We very much anticipated that, and there will be no surprise to anyone in lymphoma research by this finding," Anderson said.

"What we may not have anticipated was how fully ovarian function was achieved in younger women treated with less gonadotoxic ABVD," Anderson said.

The secondary analysis included 67 women who had participated in the RATHL trial. They were aged 18 to 45 years with histologically confirmed classic Hodgkin's lymphoma, stage IIB-IV or IIA with adverse features (bulky disease or more than two sites of involvement), no previous treatments, and a performance status of 0 to 3.

More Precise Information

In an accompanying editorial, Matteo Lambertini, MD, Institut Jules Bordet, and Isabelle Demeestere, MD, Université Libre de Bruxelles, Belgium, write that this analysis "provides more precise information than previous reports to counsel women with Hodgkin's lymphoma on gonadal damage induced by ABVD, AVD, or BEACOPP."

"They may need to receive BEACOPP if they do not respond to ABVD, so even though they may start with the less toxic regimen, they still need to be counseled, ideally at the time of their diagnosis if they are interested in having babies in the future," Lambertini said.

"This study highlights the importance of discussing access to options for fertility preservation in women older than 35 years, irrespective of chemotherapy type, and in women receiving BEACOPP, irrespective of their age," he said.