Sirolimus

Sirolimus, first isolated from a soil bacterium on Rapa Nui and originally an antifungal, was approved by the FDA in 1999 to prevent rejection of a kidney transplant. It is not a cancer drug and has no cancer indication; it belongs to this family because of what switching to it does to skin cancer risk.

TUMORAPA randomised 120 kidney transplant recipients who had already had one cutaneous squamous cell carcinoma either to switch from a calcineurin inhibitor to sirolimus or to carry on. New squamous cell carcinomas occurred in 22 per cent against 39 per cent, a relative risk of 0.56 (95 per cent confidence interval 0.32 to 0.98), with the median time to the next cancer moving from 7 to 15 months and graft function stable in both arms. The cost was 60 serious adverse events against 14 and 23 per cent stopping the drug, and switching rapidly caused twice as many serious events as switching gradually. That trade is why the switch is discussed rather than made automatically.

Sirolimus is also the drug the immunosuppression is cross-tapered to before a transplant recipient is given PD-1 blockade for advanced disease, which is how the Dana-Farber study avoided rejection. Two related records exist in the corpus: temsirolimus, its intravenous ester, and albumin-bound sirolimus, which is licensed for perivascular epithelioid cell tumour.