From the Guidelines
Switching from tacrolimus to sirolimus is strongly recommended for transplant recipients with a history of recurrent or de novo non-melanoma skin cancer, as it reduces the risk of recurrent non-melanoma skin cancer. This recommendation is based on the most recent and highest quality study, which suggests that an mTORi-based immunosuppression regimen, such as sirolimus, is beneficial in patients with a high risk of hepatic or extrahepatic cancer recurrence 1. The use of sirolimus has been shown to have anti-proliferative and anti-angiogenic properties, which can help reduce the incidence of new skin cancers and slow the growth of existing lesions.
The conversion from tacrolimus to sirolimus should be done gradually, with overlap between medications to prevent rejection, typically starting sirolimus while tacrolimus is still being administered, then slowly tapering tacrolimus as sirolimus reaches therapeutic levels (usually 5-15 ng/mL) 1. Patients should be monitored for sirolimus side effects, including hyperlipidemia, proteinuria, delayed wound healing, and mouth ulcers.
Key points to consider when switching from tacrolimus to sirolimus include:
- The protective effect against skin cancer begins within months of conversion but becomes more pronounced over time
- Sirolimus may have a specific threshold at which prevention of skin cancer is balanced with minimization of adverse events
- The switch is most beneficial for transplant patients who have already developed multiple skin cancers or have high-risk features
- The use of sirolimus is limited by a relatively high rate of discontinuation, mainly due to side effects, but the reduced risk of keratinocyte carcinoma persists when using low-dose sirolimus 1.
Overall, the switch from tacrolimus to sirolimus is a recommended approach for reducing the risk of recurrent non-melanoma skin cancer in transplant recipients, and should be considered on a case-by-case basis, taking into account the individual patient's risk factors and medical history.
From the Research
Effect of Switching from Tacrolimus to Sirolimus on Non-Melanoma Skin Cancer Risk
- The risk of recurrent non-melanoma skin cancer is significantly reduced when switching from Tacrolimus (a calcineurin inhibitor) to Sirolimus (an mTOR inhibitor) 2, 3, 4.
- A prospective, randomized, assessor-blinded, controlled clinical trial found that switching to Sirolimus-based immunosuppression inhibited the progression of premalignancies and reduced the incidence of new non-melanoma skin cancer 2.
- A meta-analysis of randomized controlled trials found that Sirolimus-based immunosuppression decreased the risk of non-melanoma skin cancer, including both squamous-cell carcinoma and basal-cell carcinoma 3.
- A retrospective study found that switching from calcineurin inhibitor to Sirolimus-based immunosuppression reduced the incidence of non-melanoma skin cancer in kidney and liver transplant recipients 4.
- A case report described a cardiac transplant recipient with recurrent non-melanoma skin cancer who experienced remission of field cancerization after conversion from calcineurin inhibitor- to Sirolimus-based immunosuppression 5.
Key Findings
- Sirolimus-based immunosuppression can delay the development of premalignancies, induce regression of preexisting lesions, and decelerate the incidence of new non-melanoma skin cancer 2.
- The risk of non-melanoma skin cancer is significantly lower in patients receiving Sirolimus-based immunosuppression compared to those receiving calcineurin inhibitor-based immunosuppression 3, 4.
- The antiproliferative effect of Sirolimus may contribute to its ability to reduce the risk of non-melanoma skin cancer 5.
Study Results
- A study found that 9 patients developed histologically confirmed non-melanoma skin cancer: 1 in the Sirolimus group and 8 in the control group (p = 0.0176) 2.
- A meta-analysis found that Sirolimus-based immunosuppression decreased the risk of non-melanoma skin cancer by 51% (RR = 0.49,95%CI 0.32-0.76, P = 0.001) 3.
- A retrospective study found that the incidence rate ratio for post versus pre-conversion non-melanoma skin cancer rates was 0.48 (0.31-0.74) in kidney transplant recipients and 0.49 (0.22-1.09) in liver transplant recipients 4.