Targeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to... Show moreTargeted therapy using EGFR inhibitors cetuximab and panitumumab has anti-tumor efficacy in colorectal cancer, though only in patients without a KRAS mutation in their tumor. This thesis aims to give insight on several aspects of EGFR inhibitors en RAS mutations in colorectal cancer. It reviews aspects of mutational analysis, aims to find ways to restore sensitivity to EGFR inhibitors in patients with KRAS mutated colorectal cancer and discusses the distinctive skin toxicity of cetuximab en pantiumumab. Show less
Krens, L.L.; Baas, J.M.; Guchelaar, H.J.; Gelderblom, H. 2018
Epidermal growth factor receptor (EGFR) inhibitors, such as the monoclonal antibodies cetuximab and panitumumab, have proven efficacy in various types of cancer. However, these agents frequently... Show moreEpidermal growth factor receptor (EGFR) inhibitors, such as the monoclonal antibodies cetuximab and panitumumab, have proven efficacy in various types of cancer. However, these agents frequently result in skin toxicity, due to the expression of the EGFR in the skin. A correlation between the occurrence of skin toxicity and anti-tumor activity has been suggested in several phase III studies. However, since skin toxicity may impair the quality of life, and severe skin toxicity requires dose reduction or interruption, adequate and timely management of skin toxicity is important to maximize the anti-tumor efficacy of the EGFR inhibitor, as well as maintaining the patient's quality of life. Due to the small number of randomized controlled trials conducted in the field of EGFR inhibitor-induced skin toxicity so far, it is not possible yet to generate evidence based guidelines on its management. Here, we review and discuss available trials and case studies reporting on the management of EGFR inhibitor-induced skin toxicity. Show less
KRAS has an important role in colorectal carcinogenesis and mutant KRAS leads to a permanently activated k-ras protein. To exert its biological activity, k-ras requires post-translational... Show moreKRAS has an important role in colorectal carcinogenesis and mutant KRAS leads to a permanently activated k-ras protein. To exert its biological activity, k-ras requires post-translational modification by prenylation. K-ras modulation has become a promising concept for new therapies, mostly by interference with the mevalonate pathway and subsequently by the prenylation of k-ras. Clinical data of agents interfering with the mevalonate pathway and the prenylation of ras are summarized and suggest that these agents might be effective when administered in combination with anticancer drugs that target k-ras. Here, we discuss the novel concept that modulation of k-ras might potentiate EGFR therapy by altering the KRAS phenotype. Show less
We present an atypical case of Cushing's syndrome caused by ectopic adrenocorticotropic hormone (ACTH) secretion in a patient with a metastasised adenocarcinoma of the oesophagus. After... Show moreWe present an atypical case of Cushing's syndrome caused by ectopic adrenocorticotropic hormone (ACTH) secretion in a patient with a metastasised adenocarcinoma of the oesophagus. After chemotherapy and surgery the patient developed generalised oedema, hyperpigmentation and dysphagia. Laboratory tests showed hypokalaemia, normal urinary potassium, increased 24-hour urinary free cortisol excretion and serum ACTH within the normal reference range. The diagnosis of ACTH-dependent Cushing's syndrome was made, most probably caused by ectopic production of ACTH. In addition to combined chemotherapy, treatment with ketoconazole sufficiently reduced urinary cortisol excretion and relieved the symptoms. Show less
