Article

Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas.

Hospices Civils de Lyon, Hôspital Edouard Herriot, Clinique Dermatologique (Pav. R), 69437 Lyon Cedex 03, France.
Anticancer research (impact factor: 1.73). 07/2009; 29(6):1927-32. pp.1927-32
Source: PubMed

ABSTRACT Immunosuppression favors the development of skin cancer. Experimental data suggest that sirolimus (SRL) has antitumoral and antiangiogenic properties. An investigation was undertaken into the effects of SRL on squamous cell carcinoma (SCC) developing in organ transplant recipients (OTR) receiving immunosuppressive treatments, with special emphasis on vascularization.
SCC that developed in eight OTR before and after conversion from calcineurin inhibitors (CNI) to SRL were compared for thickness, differentiation, ulceration, perineural invasion, density of peritumoral infiltrate, peritumoral vascularization, density of T-regulatory cells and of intratumoral Langerhans cells and growth fraction.
SCC developing under SRL showed lower peritumoral vascularization and thickness, and higher growth fraction and density of peritumoral T-regulatory cells.
Conversion from CNI to SRL at clinically relevant doses is associated in vivo with a reduced vascularization and thickness of post-transplant human cutaneous SCC. This effect could account for the beneficial effect of SRL on immunosuppression-induced skin carcinogenesis in humans.

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    Article: Sirolimus and secondary skin-cancer prevention in kidney transplantation.
    Sylvie Euvrard, Emmanuel Morelon, Lionel Rostaing, Eric Goffin, Anabelle Brocard, Isabelle Tromme, Nilufer Broeders, Veronique del Marmol, Valérie Chatelet, Anne Dompmartin, Michèle Kessler, Andreas L Serra, Günther F L Hofbauer, Claire Pouteil-Noble, Josep M Campistol, Jean Kanitakis, Adeline S Roux, Evelyne Decullier, Jacques Dantal
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    ABSTRACT: Transplant recipients in whom cutaneous squamous-cell carcinomas develop are at high risk for multiple subsequent skin cancers. Whether sirolimus is useful in the prevention of secondary skin cancer has not been assessed. In this multicenter trial, we randomly assigned transplant recipients who were taking calcineurin inhibitors and had at least one cutaneous squamous-cell carcinoma either to receive sirolimus as a substitute for calcineurin inhibitors (in 64 patients) or to maintain their initial treatment (in 56). The primary end point was survival free of squamous-cell carcinoma at 2 years. Secondary end points included the time until the onset of new squamous-cell carcinomas, occurrence of other skin tumors, graft function, and problems with sirolimus. Survival free of cutaneous squamous-cell carcinoma was significantly longer in the sirolimus group than in the calcineurin-inhibitor group. Overall, new squamous-cell carcinomas developed in 14 patients (22%) in the sirolimus group (6 after withdrawal of sirolimus) and in 22 (39%) in the calcineurin-inhibitor group (median time until onset, 15 vs. 7 months; P=0.02), with a relative risk in the sirolimus group of 0.56 (95% confidence interval, 0.32 to 0.98). There were 60 serious adverse events in the sirolimus group, as compared with 14 such events in the calcineurin-inhibitor group (average, 0.938 vs. 0.250). There were twice as many serious adverse events in patients who had been converted to sirolimus with rapid protocols as in those with progressive protocols. In the sirolimus group, 23% of patients discontinued the drug because of adverse events. Graft function remained stable in the two study groups. Switching from calcineurin inhibitors to sirolimus had an antitumoral effect among kidney-transplant recipients with previous squamous-cell carcinoma. These observations may have implications concerning immunosuppressive treatment of patients with cutaneous squamous-cell carcinomas. (Funded by Hospices Civils de Lyon and others; TUMORAPA ClinicalTrials.gov number, NCT00133887.).
    New England Journal of Medicine 07/2012; 367(4):329-39. · 53.30 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

antiangiogenic properties
 
calcineurin inhibitors
 
clinically relevant doses
 
Experimental data
 
growth fraction
 
higher growth fraction
 
humans
 
immunosuppression-induced skin carcinogenesis
 
intratumoral Langerhans cells
 
lower peritumoral vascularization
 
organ transplant recipients
 
perineural invasion
 
peritumoral T-regulatory cells
 
peritumoral vascularization
 
post-transplant human cutaneous SCC
 
reduced vascularization
 
skin cancer
 
squamous cell carcinoma
 
T-regulatory cells
 
vascularization