The Adverse Effects of Sarcoma Treatment in Cancer Survivors
Adverse events observed in sarcoma survivors highlights the increased need for new, safe treatments, as complications may not be seen until years after the completion of therapy.
Infertility is a serious and common adverse event associated with cancer treatment. Research shows that 75% of patients with sarcoma, the third most common childhood cancer, express the desire to have children later in life.1
Oncofertility, a relatively new branch of medicine, is comprised of oncologists and reproductive fertility experts. These medical professionals have developed several methods for preserving fertility through treatment completion. Both systemic and radiotherapy may contribute to the decrease in fertility for both males and females.
Alkylating agents, a class of antineoplastics known to cause infertility, can cause prolonged azoospermia by inhibiting spermatogenesis. Other drugs such as dacarbazine and taxanes, which as monotherapies can cause temporary infertility, can have an additive effect when given with an alkylating agent.
Several methods for preventing infertility are used. The most common preventative treatment for men is sperm-banking. Infertility treatment for women is, however, more complicated. Options include oocyte and embryo cryopreservation, autologous transplantation of cryopreserved tissue, and in vitro maturation of immature eggs.
The necessity to delay treatment for 2 to 4 weeks to retrieve the eggs and the possibility of losing the oocyte once the cryopreservation process has been completed are, however, undesirable.
Both autologous transplantation of cryopreserved tissue and in vitro maturation of immature eggs remain experimental. Further data on the efficacy and safety of the procedures are necessary before widespread use can be recommended.
New molecular targeted therapy may also be fertility-protective in animal studies, though human studies are required. Rinaldi et al note, for example, that inhibition of checkpoint kinase 2 (CHK2), a key element of oocyte DNA damage checkpoint response, is being evaluated for potential pharmacological preservation of ovarian function.
The study found that while radiation exposure resulted in eradication of immature oocytes in wild-type mice, the same exposure in CHK2-inhibited mice led to oocytes-retention, suggesting that “chemical inhibition of CHK2 is a potentially effective treatment for preserving fertility and ovarian endocrine function of women exposed to DNA-damaging cancer therapies.”3
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Another major side effect of chemotherapy in patients with sarcoma is cardiotoxicity. Research shows that doxorubicin-associated cardiotoxicity is dose-dependent. The cumulative dose of 450 mg/m2 is associated with acute cardiomyopathy during chemotherapy treatment, as well as late cardiomyopathy and death in the decades to follow. Trials using doxorubicin show significant alteration and discontinuation of therapy due to cardiotoxicity induced by the medication.