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Benson C.,Sarcoma Unit | Vitfell-rasmussen J.,Herlev Hospital | Maruzzo M.,Sarcoma Unit | Fisher C.,Royal Marsden NHS Foundation Trust | And 6 more authors.
Anticancer Research | Year: 2014

Perivascular epithelioid cell tumors (PEComas) are rare tumors driven by tuberous sclerosis complex gene mutations causing up-regulation of mTOR. We report the outcome of ten consecutive patients treated with sirolimus or temsirolimus. Patients and Methods: A retrospective analysis was performed on patients seen between 2007 and 2013. Demographic and treatment data were collected and radiological response was assessed. Results: Ten patients were investigated, eight females, with median age of 47.5 years. Nine patients received sirolimus, one temsirolimus. The median treatment duration was 128 (range=7-1,366 days). Temsirolimus was given at 25 mg IV weekly and median starting dose of sirolimus was 3 mg daily. Seven patients were evaluable for response by RECIST: 5 showed partial response (50%), 1 stable disease (10%) and 1 progressive disease (10%). Two patients progressed rapidly on treatment. One patient stopped due to grade 3 hyperlipidaemia although CT scan shows maintained response. Three patients continue on treatment while the remainder stopped due to disease progression. Conclusion: Our study confirms that mTOR inhibition with sirolimus/temsirolimus is well-tolerated with good radiological responses, albeit short-lived, and supports its use in PEComas. Source

Martin-Liberal J.,Renal and Melanoma Unit | Furness A.J.S.,Renal and Melanoma Unit | Furness A.J.S.,University College London | Joshi K.,Renal and Melanoma Unit | And 4 more authors.
Cancer Immunology, Immunotherapy | Year: 2015

The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. Immune checkpoint inhibitors such as these can induce endocrine adverse events but autoimmune diabetes has not been described to date. However, there is a strong preclinical rationale that supports this autoimmune toxicity. We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. The presence of high serum titres of anti-glutamic acid decarboxylase antibodies together with a suggestive clinical presentation, age of the patient and preclinical data strongly support an autoimmune aetiology of the diabetes. Moreover, the patient was found to have a well-known high-risk human leucocyte antigen type for the development of type 1 diabetes in children, so the PD-1 inhibition is very likely to have triggered the autoimmune phenomenon. Our case suggests that insulin-dependent diabetes might be a rare but important anti-PD-1 immune-related adverse event. © 2015, Springer-Verlag Berlin Heidelberg. Source

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