Prospective evaluation of major vascular events in patients with nonsmall cell lung carcinoma treated with cisplatin and gemcitabine

Abstract

BACKGROUNDCancer and cisplatin‐based chemotherapy both are well recognized risk factors for coagulation disorders and thrombosis. However, vascular events (VEs) seldom are considered adverse effects of treatment and may not even be taken into account in reports of chemotherapy trials.METHODSVEs were recorded prospectively in a population of patients with nonsmall‐cell lung carcinoma (NSCLC) who were treated consecutively with cisplatin and gemcitabine using a diagnostic flow chart based on a thorough clinical examination, hematologic and coagulative parameters, and imaging assessments when appropriate.RESULTSFrom January, 2000 to January 2003, 108 patients with Stage III–IV NSCLC underwent chemotherapy and were evaluated. Overall, 22 VEs occurred in 19 patients (17.6%; 95% confidence interval [95% CI], 10.3–24.8%), including 10 arterial VEs (2 myocardial infarctions, 7 lower limb arterial thrombosis, and 1 ischemic stroke) and 12 venous VEs (3 catheter‐related upper limb VEs, 6 venous thrombosis of the lower limb, and 3 pulmonary embolisms). The cumulative proportion of VEs at 1 year after the start of chemotherapy was 22.0% (95% CI, 12.7–31.3%). Four patients died due to the VE (overall mortality, 3.7%), and 3 patients needed surgical revascularization. In the other patients, conservative medical treatment was effective. Baseline patient‐related and disease‐related characteristics of the patients with VEs did not differ significantly from the characteristics of patients without VE; liver and brain metastases were more frequent in patients with VE, although the difference did not reach statistical significance. Response rates were similar in the two groups. A double VE was detected in three patients who were given further chemotherapy after resolution of the first event.CONCLUSIONSVEs were a common finding in chemotherapy‐treated NSCLC patients. Chemotherapy itself seem to be a powerful risk factor for VE. Strategies to predict the occurrence of VEs should be developed to spare this life‐threatening toxicity. Cancer 2005. © 2005 American Cancer Society.

Acute Aortic Thrombosis in Patients Receiving Cisplatin-Based Chemotherapy

“…Importantly, as in the cases described here, symptoms may be absent or minimal. Interestingly, events tended to occur later in the treatment course, which varies from the descriptions in previous reports 5,7,9,11 . The patient reported by Morlese et al 9 presented with an acute symptomatic thrombus in a non-atheromatous abdominal aorta, and a separate thrombus in the left ventricle 24 hours after cisplatin infusion for treatment of esophageal adenocarcinoma.…”

“…Cisplatin is known to increase the risk of thromboembolic events and is the agent most commonly implicated in patients with cancer and arterial thrombosis 9,10 . Cisplatin-induced vascular events tend to occur early in the course of treatment, with approximately 45% occurring during the first 2 courses of chemotherapy 5 . The mechanism by which cisplatin triggers vascular events is unknown, but endothelial damage seems to play a major role.…”

“…The mechanism by which cisplatin triggers vascular events is unknown, but endothelial damage seems to play a major role. Other proposed hypotheses are cisplatin-induced elevation of plasma levels of von Willebrand factor and drug-induced reduction of left ventricular function 4,5,7,8 . Cisplatin is known to cause hypomagnesemia, which has been implicated in vascular events.…”

“…In fact, most cases of cisplatin-induced arterial thrombosis described in the literature occurred in patients with at least one of the foregoing risk factors 4,5,7,8 . None of the 4 patients described here had clinical evidence of significant peripheral vascular disease, and ct imaging demonstrated no chronic abnormalities in the abdominal aorta, such as aneurysm or atherosclerotic disease, nor enlarged lymph nodes or tumoural masses causing extrinsic compression of the abdominal aorta.…”

Acute Ischemic Stroke Developing in the Course of Cisplatin Treatment of Small Cell Lung Cancer: A Case Report

“…[9] Sonuçta sisplatine bağlı iskemik inmenin nadir olduğu düşünülmektedir ve bu konuda bildirilmiş olgular vardır. [10][11][12] Sisplatine bağlı vasküler olayların (arteriyel veya venöz) %45'inin ilk iki kemoterapi esnasında ortaya çıktığı ve arteriyel olanların venözlerden daha erken ortaya çıktığı bildirilmiştir. [13] Her ne kadar ilk kemoterapiden sonra daha sık görülse de sisplatine bağlı iskemik inme kanser tipinden bağımsız olarak tedavi baş-langıcından sonraki ilk on gün içinde ortaya çıkabilir.…”