Photo courtesy of UW Health
The heart medication dexrazoxane can protect fertility and improve survival in female mice receiving the chemotherapeutic agent doxorubicin, according to research published in PLOS ONE.
Dexrazoxane prevented ovarian damage, increased the number of healthy offspring mice had, and prolonged their survival.
If dexrazoxane has the same effects in humans, it could save young lives while also overcoming limitations to fertility treatments currently used during cancer treatment, according to study author Sana Salih, MD, of the University of Wisconsin School of Medicine and Public Health in Madison.
“Fertility preservation following chemotherapy for children and women diagnosed with cancer is a formidable challenge,” Dr Salih said. “For pre-pubescent girls, the only option to prevent chemo-induced ovarian failure is to preserve ovarian tissue by freezing.”
Unfortunately, that is an experimental procedure that requires surgery to harvest and again to re-implant the tissue after cancer treatment. The transplantation carries a small risk of cancer recurrence and provides only a short-term solution.
“The transplanted ovarian tissue can only function for 3 to 7 years,” Dr Salih said.
So she was pleased to discover that pre-administration of dexrazoxane diminished ovarian damage and preserved ovarian function and fertility in mice whose ovaries were exposed to doxorubicin.
“What really surprised us is that a very small dose of dexrazoxane was enough to give full ovarian protection,” Dr Salih said.
Mice treated with dexrazoxane also gave birth to healthier litters, with more pups and higher birth weights than mice that received doxorubicin alone.
In addition, the mice that received dexrazoxane and doxorubicin lived much longer than mice that only received doxorubicin. And mice given only dexrazoxane lived longer than control mice receiving no interventions.
“The [US Food and Drug Administration] currently limits the use of dexrazoxane to adults to protect their hearts from the toxic side effects of chemotherapy,” Dr Salih said. “But these patients are receiving very high doses of dexrazoxane that may actually be contributing to increased toxicity, leading to decreased survival in some patients.”
Dr Salih and her colleagues found they could achieve high mouse survival rates, ovarian protection, and birthing successes using a dose of dexrazoxane 10 times lower than what is used for adult human cardiac protection. Post-mortem studies on the mice showed protection of ovarian, heart, and other cells and tissues.
“This is exciting,” Dr Salih said. “We are now submitting a grant to look at low-dose dexrazoxane protection in nonhuman primates as a stepping stone to clinical translation in pediatric cancer patients.”
Dr Salih has begun studies needed to show that safe doses of dexrazoxane can protect developing primate ovaries. Nonhuman primate ovarian development, cycle time, and gestation are very similar to that of humans.
“My goal is to present data so that physicians can come up with dosage recommendations and safety profiles for early clinical trials in humans,” Dr Salih said. “Up to 6% of young girls with childhood cancers and 50% of women with breast cancer who endure chemotherapy face ovarian failure. We need to give more cancer survivors real hope that they can conceive a healthy child.”
