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School of Medicine, Gazi University, Department of Medical Oncology, Gazi Hospital, 06500 Besevler, Ankara, Turkey, fax +90 312 2158710, ramazanstar{at}yahoo.com
Associate Professor, School of Medicine, Gazi University, Department of Medical Oncology, Gazi Hospital
School of Medicine, Gazi University, Department of Medical Oncology, Gazi Hospital
School of Medicine, Gazi University, Department of Medical Oncology, Gazi Hospital
School of Medicine, Department of Medical Oncology, Gazi University, Gazi Hospital
Published Online, April 3, 2007. www.theannals.com, DOI 10.1345/aph.1K055
Case Report. A 59-year-old male patient presented with an irregular mass in the anterior segment of the superior lobe of his left lung and multiple conglomerated mediastinal adenopathies as revealed on computed tomography (CT) scan. Adenocarcinoma was diagnosed through bronchoscopy and biopsy. Positron emission tomography/CT showed increased 18F-FDG uptake in multiple sites of the body, indicating metastatic disease. He had a smoking history of 30 pack-years and no history of cardiovascular or thromboembolic disorders or diabetes. Gemcitabine was started as monotherapy (1250 mg/m2 on days 1 and 8 every 3 wk) because of poor performance status as indicated by the score (2) on the Eastern Cooperative Oncology Group scale. After the first dose of gemcitabine, the patient noted painless color changes in the fingertips of his digits on the second day of treatment; this almost resolved completely in a week. One day after the second dose of gemcitabine, the patient complained of pain and more color changes in his digits. Physical examination revealed ischemic changes on inspection and pain on palpation of the fingers of both hands. Results of complete blood cell count, liver function, and renal function tests were normal, and there were no signs of hemolysis or hemostasis. Erythrocyte sedimentation rate was 37 mm/h. Antinuclear antibodies, anti-DNA, C3 and C4, protein C, and protein S activities were normal, as were arterial Doppler ultrasound studies of upper extremities. Peripheral vasodilator agents were given and low-molecular-weight heparin and aspirin were started for prophylaxis. Gemcitabine was stopped, and the patient's signs and symptoms resolved partially in a week. Another chemotherapeutic agent was then given for further cancer treatment. The Naranjo probability scale indicated a probable relationship between digital ischemia and gemcitabine therapy in this patient.2
Discussion. Four cases of distal ischemic changes related to combination chemotherapy with cisplatin and gemcitabine were reported by Barcelo et al.1 In most of those patients, gemcitabine was used in combination with platinum salts, patients had diagnosed autoimmune disorders, or increased auto: antibody ratios were demonstrated. Unlike those case reports, gemcitabine was given to our patient as a single agent in first-line therapy, and autoimmune markers were negative at that time.
After gemcitabine therapy, painful digital ischemic changes similar to those in Raynaud's phenomenon were observed in our patient. The occurrence of ischemia as a paraneoplastic syndrome,3 endothelial damage secondary to inflammatory changes,4 and thrombotic microangiopathy5 after gemcitabine treatment has been reported. Main diagnostic parameters of thrombotic microangiopathy were normal for our patient. Endothelial damage and paraneoplastic syndrome may be possible underlying mechanisms for the pathogenesis of digital ischemia, but smoking history, undiagnosed autoimmune disorders, and thrombotic microangiopathy could not be ruled out. Peripheral ischemia is rare in patients with cancer; however, clinicians should monitor patients receiving gemcitabine for this adverse reaction.
References
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