A multi-center trial found that, acceptance the
PRKAR1A sirolimus immunosuppressants in renal transplant patients with skin cancer, the likelihood of more small compared with the early calcineurin inhibitor. According to the French HospicesCivils de Lyon in Lyon, MD, Sylvie Euvrard and colleagues, compared with those patients taking cyclosporine or tacrolimus, patients receiving sirolimus therapy the risk of occurrence of new squamous Prkar2b cell carcinoma reduced by half (RR 0.56, 95% CI 0.32 to 0.98) .7 26 January, the researchers report in the New England Journal of Medicine said, accepting the sirolimus group of skin tumors was delayed (more than seven in 15 months months, P = 0.02).Skin cancer, immune suppression after organ transplantation often happens, the first is the emergence of squamous cell carcinoma, while in the process of Prkca immune suppression often change. Sirolimus is the work of Napa neomycin inhibit the mammalian target. It has anti-tumor effect, a small number of studies have shown that it may reduce the probability of organ transplant patients with skin cancer.
In order to study the early emergence of invasive squamous PRKCB cell carcinoma patients change from calcineurin inhibitors to sirolimus, Euvrard and colleagues of 120 patients registered in the three open trials, these participants were randomly allocated to continue using cyclosporine or tacrolimus, or into a sirolimus. Two years of research, the participants every three months will be evaluated once. Over 3/4 of the study participants were men, mean age was 63 years old. In 120 patients, a total of 290 squamous cell carcinomas and 274 PRKCD skin tumors such as basal cell carcinoma has been confirmed. 55% of the tumor is single, 45% of the tumor is more than one cancer injury. At the time of registration, 86 patients are using cyclosporine, 36 patients using sirolimus.Purpose of cyclosporine levels is 75ng/mL-125ng/mL Tacrolimus is 4ng/mL-7ng/mL, sirolimus 6ng/mL-12ng/mL. Calcineurin inhibitors stop using the change in a week or within a week of sirolimus were classified as fast-if the use of calcineurin inhibitors for more than a week, were classified as progressive.The 2-year follow-up time, the sirolimus group, 22% of the occurrence of new squamous cell carcinoma in the calcineurin inhibitor group, the proportion is 39%, the risk of new tumors in significant changes in patients reduced (0.37, 95% CI 0.16 to 0.85) compared with calcineurin inhibitors with calcium, the use of sirolimus to maintain without the possibility of a new squamous cell carcinoma is more for those patients with only a single injury. but not so great for those patients with multiple injuries. In this study, a total of 86 patients completed the full two years of research. Among them, 70.5% of those receiving calcineurin inhibitors in the treatment of patients new squamous cell tumors, compared with 47.6% receiving sirolimus group. Seven non-skin cancer in the history of a relapse, there were six patients with no previous history of occurrence of new squamous skin tumors.The researchers said the study transplantation resisters, there is no low level which indicates that treatment with sirolimus immunosuppression after. Almost all patients have the least side effects, including edema, acne, mouth ulcers and proteinuria in the first six months of taking sirolimus. 60 serious adverse events occurred in the sirolimus group, 14 people in the calcineurin inhibitor group. In the sirolimus group, 23% because of the emergence of side effects the termination of drug use. Compared with the progressive change, the more rapid changes to the sirolimus patients to terminate the use of the drug. Rapid changes also led to the occurrence of serious side effects a higher probability (65% versus 30%, P = 0.01) and pneumonia (30% versus 11%). Euvrard and colleagues statement said: "Although the frequency of serious adverse reactions in the sirolimus group (0.94 / person) than in the calcineurin inhibitor group (0.25 / person) was significantly higher, but the skin squamous cell the number of cancer has decreased a factor of 3.4. "They say they can not be directly compared between the two groups the level of immunosuppression, but to study drug purposes always in purpose within.They wrote: "We speculate that sirolimus, there is a special kind of anti-tumor activity, this phenomenon can be explained by the reduction of new skin cancer, not because of immunosuppression reduced. The possible role of sirolimus The mechanisms of angiogenesis and inhibition of cell proliferation, also belong to the antiviral effect.
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