Credit: Rhoda Baer
A mathematical formula may help physicians predict which cancer survivors are likely to have normal sperm production following chemotherapy with alkylating agents.
Researchers developed the formula to calculate survivors’ cumulative treatment exposure to alkylating agents as a cyclophosphamide-equivalent dose (CED).
The team used this formula to evaluate a cohort of cancer survivors and found that CEDs of 4 g/m2 or less were associated with normal sperm concentrations.
An account of this research was published in The Lancet Oncology.
“Based on these results, we would recommend pretreatment fertility preservation be offered, whenever clinically possible, to any male whose projected treatment is expected to include a cyclophosphamide-equivalent dose greater than 4 g/m2,” said study author Daniel Green, MD, of St Jude Children’s Research Hospital in Memphis, Tennessee.
Dr Green and his colleagues had studied 214 male survivors of childhood cancer who had a median age of 29. Subjects had received cyclophosphamide and other alkylating agents, but their treatment did not include radiation.
The researchers performed semen analysis in the survivors a median of 21 years from their diagnosis. The analysis showed that 47.6% of survivors had normal sperm concentrations (at least 15 million per milliliter), 27.6% had low sperm counts, and 24.8% produced no sperm.
To determine the impact of alkylating agents on the survivors’ sperm production, the researchers calculated each survivor’s cumulative treatment exposure as a CED.
They did this using the following formula: CED (mg/m2)= 1.0 (cumulative cyclophosphamide dose [mg/m2]) + 0.244 (cumulative ifosfamide dose [mg/m2]) + 0.857 (cumulative procarbazine dose [mg/m2]) + 14.286 (cumulative chlorambucil dose [mg/m2]) + 15.0 (cumulative carmustine dose [mg/m2]) + 16.0 (cumulative lomustine dose [mg/m2]) + 40 (cumulative melphalan dose [mg/m2]) + 50 (cumulative thiotepa dose [mg/m2]) + 100 cumulative chlormethine dose [mg/m2]) + 8.823 (cumulative busulfan dose [mg/m2]).
The researchers could not identify a uniformly safe or toxic dose of these drugs, but they found that survivor sperm concentrations generally decreased as cumulative exposure to alkylating agents increased.
And CEDs of 4 g/m2 or less were associated with normal sperm concentrations. Almost 89% of survivors whose CED was 4 g/m2 or less had a normal sperm count. Their sperm were also more likely than sperm from other survivors to look and behave normally.
Dr Green did note that, although a lower cumulative dose of alkylating agents was associated with normal sperm production, outcomes for individual patients were unpredictable and varied.
