Management of Solid OrganTransplant Recipients With Skin Cancer
Background: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest.
Objectives: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
Methods: Three electronic databases were searched for relevant trials: MEDLINE (1966October 2003), EMBASE (1980week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review.
Results: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up.
Conclusions: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the riskbenefit ratio.
The increased incidence of skin cancers after solid organ transplantation is well recognized. In renal transplant recipients in Australia, the cumulative incidence increases with number of years post-transplantation, from 7% after 1 year of immunosuppression, to 45% after 11 years, to 70% after 20 years. Increased incidences of post-transplant skin cancers have also been demonstrated in cardiothoracic and liver transplants. The magnitude of the increased risk varies with the type of skin cancer. Data from the Netherlands suggest that the overall incidence of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in transplant recipients is 250 and 10 times higher, respectively, when compared with the general population. These skin cancers result in considerable morbidity as individual patients often develop multiple tumours. In addition, skin cancers developing in transplant recipients are more aggressive, accounting for 27% of all deaths after the fourth year in an Australian cardiac transplant population.
The management of skin cancers within this population is therefore a significant issue. Education, prevention through sun-avoidance measures, and early detection and treatment have been the mainstay of management. In the past decade, interest has increased in the use of oral retinoids to reduce and delay the development of cutaneous neoplasms. The mechanism of action of these agents remains under investigation. Retinoids act via cellular retinoid receptors to alter gene transcription. Known effects of retinoids include immunomodulation, antikeratinization, induction of apoptosis and antiproliferation. An open-label uncontrolled study reported a beneficial effect of etretinate in the management of malignant cutaneous lesions in six renal transplant recipients. Acitretin is an oral retinoid that has replaced etretinate. Small uncontrolled studies suggest that it may be equally effective in the management of skin cancers in the transplant setting. The magnitude of the benefits and risks associated with the use of oral retinoids for the prevention of skin cancers in this setting remains poorly defined, and not every transplant patient is commenced on this therapy. The objective of this review is to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
Background: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest.
Objectives: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
Methods: Three electronic databases were searched for relevant trials: MEDLINE (1966October 2003), EMBASE (1980week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review.
Results: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up.
Conclusions: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the riskbenefit ratio.
The increased incidence of skin cancers after solid organ transplantation is well recognized. In renal transplant recipients in Australia, the cumulative incidence increases with number of years post-transplantation, from 7% after 1 year of immunosuppression, to 45% after 11 years, to 70% after 20 years. Increased incidences of post-transplant skin cancers have also been demonstrated in cardiothoracic and liver transplants. The magnitude of the increased risk varies with the type of skin cancer. Data from the Netherlands suggest that the overall incidence of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in transplant recipients is 250 and 10 times higher, respectively, when compared with the general population. These skin cancers result in considerable morbidity as individual patients often develop multiple tumours. In addition, skin cancers developing in transplant recipients are more aggressive, accounting for 27% of all deaths after the fourth year in an Australian cardiac transplant population.
The management of skin cancers within this population is therefore a significant issue. Education, prevention through sun-avoidance measures, and early detection and treatment have been the mainstay of management. In the past decade, interest has increased in the use of oral retinoids to reduce and delay the development of cutaneous neoplasms. The mechanism of action of these agents remains under investigation. Retinoids act via cellular retinoid receptors to alter gene transcription. Known effects of retinoids include immunomodulation, antikeratinization, induction of apoptosis and antiproliferation. An open-label uncontrolled study reported a beneficial effect of etretinate in the management of malignant cutaneous lesions in six renal transplant recipients. Acitretin is an oral retinoid that has replaced etretinate. Small uncontrolled studies suggest that it may be equally effective in the management of skin cancers in the transplant setting. The magnitude of the benefits and risks associated with the use of oral retinoids for the prevention of skin cancers in this setting remains poorly defined, and not every transplant patient is commenced on this therapy. The objective of this review is to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population.
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