Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus.
OBJECTIVE
In light of the significant morbidity and mortality of cutaneous invasive squamous cell carcinomas (SCCs) in renal transplant recipients, we investigated whether conversion to sirolimus-based immunosuppression from standard immunosuppression could diminish the recurrence rate of these skin cancers.


METHODS
In a 2-year randomized controlled trial, 155 renal transplant recipients with at least one biopsy-confirmed SCC were stratified according to age (< 55 v ≥ 55 years) and number of previous SCCs (one to nine v ≥ 10) and randomly assigned to conversion to sirolimus (n = 74) or continuation of their original immunosuppression (n = 81). Development of a new SCC within 2 years after random assignment was the primary end point.


RESULTS
After 2 years of follow-up, the risk reduction of new SCCs in the multivariable analysis was not significant, with a hazard ratio (HR) of 0.76 (95% CI, 0.48 to 1.2; P = .255), compared with a non-sirolimus-based regimen. After the first year, there was a significant 50% risk reduction, with an HR of 0.50 (95% CI, 0.28 to 0.90; P = .021) for all patients together and an HR of 0.11 (95% CI, 0.01 to 0.94; P = .044) for patients with only one previous SCC. The tumor burden of SCC was reduced during the 2-year follow-up period in those receiving sirolimus (0.82 v 1.38 per year; HR, 0.51; 95% CI, 0.32 to 0.82; P = .006) if adjusted for the number of previous SCCs and age. Twenty-nine patients stopped taking sirolimus because of various adverse events.


CONCLUSIONS
Conversion to sirolimus-based immunosuppression failed to show a benefit in terms of SCC-free survival at 2 years.
Nijmegen Medical Center, Radboud University, Nijmegen, the Netherlands.
Judith M
JM
Hoogendijk-van den Akker
Paul N
PN
Harden
Andries J
AJ
Hoitsma
Charlotte M
CM
Proby
Ron
R
Wolterbeek
Jan Nico
JN
Bouwes Bavinck
Johan W
JW
de Fijter
D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000139:chemically induced; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
D007166:Immunosuppressive Agents; D020123:Sirolimus