Association of creatine kinase and skin toxicity in phase I trials of anticancer agents.

BACKGROUND: We investigated the association between skin rash and plasma creatine kinase (CK) levels in oncology phase I trials. METHODS: We analysed data from 295 patients treated at our institution within 25 phase I trials which included CK measurements in the protocol. Trials involved drugs targeting EGFR/HER2, m-TOR, VEGFR, SRC/ABL, aurora kinase, BRAF/MEK, PARP, CDK, A5B1 integrin, as well as oncolytic viruses and vascular disrupting agents. RESULTS: Creatine kinase measurements were available for 278 patients. The highest levels of plasma CK during the trial were seen among patients with Grade (G) 2/3 rash (median 249 U l(-1)) compared with G1 (median 81 U l(-1)) and no rash (median 55 U l(-1)) (P<0.001). There was a significant reduction in CK after the rash resolved (mean 264.2 vs 100.1; P=0.012) in 25 patients, where serial CK values were available. In vitro exposure of human keratinocytes to EGFR, MEK and a PI3Kinase/m-TOR inhibitor led to the increased expression of CK-brain and not CK-muscle or mitochondrial-CK. CONCLUSION: Plasma CK elevation is associated with development of skin rash caused by novel anticancer agents. This should be studied further to characterise different isoforms as this will change the way we report adverse events in oncology phase I clinical trials

Autoimmune hepatitis in children in Eastern Denmark

Objectives: Autoimmune hepatitis (AIH) in childhood is a progressive chronic inflammatory liver disease. The aim of this study was to compare the clinical and biochemical characteristics of 33 paediatric patients diagnosed as having AIH with earlier described cohorts, and to examine the effect of early treatment strategies on the course of disease. Methods: A population-based cohort of patients from January 1993 to September 2009 was identified prospectively, and the patient data were collected by a retrospective examination of the files. Results: Twenty-nine patients had type 1 AIH, 2 had type 2, and 2 could not be categorised. Among the 33 children, 16 (48.5%) were girls and 17 (51.5%) were boys. Twenty-three (69.7%) of the patients had symptoms at presentation indistinguishable from acute viral hepatitis, but in 16 (69.6%) of those the liver biopsy showed cirrhosis. Twenty (60.6%) patients were treated with prednisolone and azathioprine at the time of remission, whereas 8 (24.2%) were treated with prednisolone. One (3%) patient did not experience remission during the observation period. Conclusions: The patients in our study appeared similar to previously published cohorts, although a female predominance was not observed. Our data suggest that early treatment including both prednisolone and azathioprine could be more effective than prednisolone alone, even if randomised controlled paediatric studies comparing these 2 different treatment regimens are needed