case report Digital ischemic events related to gemcitabine: Report of two cases and a systematic review Cvetka Grasic Kuhar, Tanja Mesti, Branko Zakotnik Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia Received 1 February 2010 Accepted 1 March 2010 Correspondence to: Cvetka Grasič Kuhar, MD. PhD, Department of Medical Oncology, Institute of Oncology Ljubljana, Zaloška c. 2, SI-1000 Ljubljana, Slovenia; Phone: +386 1 5879282; Fax: +386 1 5879305; E-mail: cgrasic@onko-i.si Disclosure: No potential conflicts of interest were disclosed. Background. Gemcitabine is a potent cytotoxic agent used in the treatment of many solid tumours, sarcomas and lymphomas. Vascular toxicity and thrombotic events related to gemcitabine seem to be underreported. Case report. We report two cases of gemcitabine related digital ischemic events. Case 1. A 65-year-old man was given the first-line treatment with gemcitabine for the advanced adenocarcinoma of pancreas. After four weekly doses of gemcitabine (total dose 4000 mg/m2) he presented with Raynaud’s like phenom- enon and ischemic fingertips necrosis in five digits of both hands. Symptoms resolved in all but one digit after stopping chemotherapy and treatment with iloprost trometamol infusion. Case 2. A 77-year-old man, ex-smoker, was administered a combination of gemcitabine and cisplatin as the first-line treatment for the locally advanced bladder cancer. After 4 cycles of the treatment (total dose of gemcitabine 4000 mg/m2) the patient suffered digital ischemia and necrosis on two digits of a right leg. Arteriography revealed preex- isting peripheral arterial occlusive disease (PAOD) of both legs with very good peripheral collateral circulation and absent microcirculation of affected two digits. The gemcitabine treatment was stopped and the patient was treated with iloprost trometamol infusion and percutaneous transluminal angioplasty with dilatation of the right superficial femoral artery. Digital changes resolved without consequences. Severe thrombocytosis (platelet count 1211 x 109/L) might have also contributed to the ischemic digital event in the second case. Conclusions. Digital ischemic events associated with gemcitabine chemotherapy seem to be more common in patients with tobacco-associated cancers, especially when used in combination with platinum salt. The treatment with gemcitabine in patients with evolving Raynaud’s phenomenon and/or preexisting PAOD should be done with caution. Key words: chemotherapy; gemcitabine vascular toxicity; digital ischemic events Introduction Gemcitabine is an important contemporary chem- otherapeutic agent for the treatment of both solid tumours and lymphomas.1 As a nucleoside analog structurally related to cytosine arabinoside, it in- terferes with the synthetic pathways of the tumour cell predominantly in the S phase of the cell cycle. It is a potent inhibitor of DNA synthesis and re- pair.2 First approved in 1996 for the treatment of un- resectable pancreatic cancer, today gemcitabine is most commonly used in the therapy of pancreatic, ovarian, breast, non-small cell lung and bladder cancer, some sarcomas, cutaneous and peripheral T-cell lymphomas as well as in relapsed Hodgkin’s lymphoma.1 The use of this drug enables progress in the routine management of cancer patients.3,4 Gemcitabine is a drug with a favourable toxic- ity profile with myelosuppression, a flu-like syn- drome, skin rash and radiation recall dermatitis being the most common side effects.2 As indications for its use in oncology have been expanding, some reports showed the possibility of its vascular side effects. Among them throm- botic microangiopathy5, venous thrombembolism, acute arterial events (digital ischemia and necrosis, vasculitis), systemic capillary leak syndrome and Radiol Oncol 2010; 44(4): 257-261. doi:10.2478/v10019-010-0020-1 257