Year: 2009
Type: letter
Abstract: We welcome the insightful contribution of Pirl et al 1 to the growing literature on the potential neuropsychiatric effects of molecular-targeted cancer therapies.As Pirl et al appropriately point out, the term tyrosine kinase inhibitors (TKIs) was used in our initial paper to refer to a variety of small molecule drugs with activity against a number of different receptor and nonreceptor tyrosine kinases, including imatinib (inhibitory against ABL, BCR-ABL, KIT, and platelet-derived growth factor receptors [PDGFRs]), sunitinib (inhibitory against KIT, PDGFRs, and vascular endothelial growth factor receptors), and dasatinib (inhibitory against ABL, BCR-ABL, SRC, KIT and PDGFRs).Our observations may indeed be quite different from what one might expect to see with the exquisitely specific drugs, such as gefitinib or erlotinib, which inhibit the epidermal growth factor receptor (EGFR).Interestingly, small-molecule TKIs targeting EGFR tend to be far more specific for this receptor tyrosine kinase than for other kinase targets, probably reflecting a unique structural biology for the adenosine triphosphate-binding pocket in the EGFR.Moreover, our observations were derived solely from our team's extensive experience managing GI stromal tumor, one of the three major diseases managed with drugs in this class (the others being chronic myelogenous leukemia and renal cell carcinoma).Of note, links between depression and specific drug exposure may be missed in large database analyses, for multiple reasons.Most importantly, the linkage may be idiosyncratic and/or uncommon.Our observations suggest the incidence of imatinib-associated depression in the GI stromal tumor population to be no more than 2%; many toxicity analyses are reported only if the toxicity is severe or if it occurs in at least 5% to 10% of exposed patients.Second, if the possibility of causality from drug is not considered, depression in a patient suffering from advanced cancer may not be scored as a drug-associated toxicity.Only after recognition of the syndrome in patient 1 were we able to consider and subsequently clinically confirm the diagnosis in other patients in the series.Until further studies are conducted, because of the high morbidity and mortality associated with underdiagnosed and undertreated depression, we believe that the possibility of drug induc-tion of depression or other mood changes should be considered in the differential diagnosis of psychological distress in patients treated with these agents.
Source: Journal of Clinical Oncology
Language: French
Topic: Cancer survivorship and care
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2168956768