Gemcitabine: vascular toxicity and prothrombotic potential

BACKGROUND: Gemcitabine has been associated with important thrombotic and vascular side effects. As indications for its use in oncology and hematology are expanding, comprehensive characterization of these complications becomes imperative. OBJECTIVE: This article reviews the prothrombotic potential and other vascular effects of gemcitabine and experience accrued through its use in research laboratories, clinical trials and clinical practice. METHODS: The most relevant publications were identified through the PubMed database and by reviewing the drug information released by the FDA. RESULTS/CONCLUSIONS: In the author's opinion, the incidence of thrombotic and vascular toxicity with gemcitabine is higher than previously estimated. Venous thromboembolism (VTE) and acute arterial events, digital ischemia and necrosis, vasculitis and thrombotic microangiopathy, potentially fatal systemic capillary leak and reversible posterior leukoencephalopathy syndromes are only a few items on the long list of vascular-toxic effects of gemcitabine. These toxicities seem to be more frequent with the use of gemcitabine-platinum doublets than with gemcitabine alone. Careful consideration of gemcitabine use should be given in the setting of pre-existing arterial vascular disease, venous thromboembolism, collagenoses, heart failure, liver damage and advanced hepatic metastases. Specific treatment requirements of individual patients, their comorbidities and the gemcitabine risk:benefit ratio should be always sought before using this agent in antineoplastic therapy.