Cisplatin Significantly Increases Risk of VTEs in Patients with Advanced Solid Tumors

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(ChemotherapyAdvisor) – Patients with advanced solid tumors treated with cisplatin have a significant increased risk of venous thromboembolism compared with non–cisplatin-based chemotherapy, according to a systematic review and analysis in the Journal of Clinical Oncology online November 11.

“Patients with cancer have a four- to eight-fold higher risk of venous thromboembolic events (VTEs) than age-matched controls,” noted Matthew D. Galsky, MD, of The Tisch Cancer Institute at Mount Sinai Medical Center, New York, NY, and colleagues. “To our knowledge, this is the largest study evaluating the excess risk of VTEs with cisplatin-based chemotherapy.”

Although several clinical characteristics and cancer treatment—including cisplatin—have been associated with increased VTE rates, this risk has not previously been well described.

A PubMed search for articles published from January 1, 1990, to December 31, 2010, identified 8,216 patients with solid tumors in 38 prospective randomized phase II and III trials that evaluated cisplatin-based vs non–cisplatin-based chemotherapy, from which data on on-grade VTEs were extracted.

In patients treated with cisplatin-based chemotherapy, incidence of VTEs was 1.92% (95% CI 1.07–2.76) vs 0.79% (95% CI 0.45–1.13) for those treated with non–cisplatin-based regimens.

“Patients receiving cisplatin-based chemotherapy had a significantly increased risk of VTEs (RR 1.67; 95% CI 1.25–2.23; P=0.01),” they found. The highest risk of VTEs was found to be in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.71; 95% CI, 1.17–6.30; P=0.02) and in trials reported during 2000 to 2010 (1.72; 95% CI 1.27–2.34; P=0.01).

“These findings should be viewed in the context of a recent meta-analysis suggesting a 1.33-fold increased risk of VTEs with bevacizumab, an anti-vascular endothelial growth factor receptor antibody, which has been used for decades less frequently than cisplatin to treat a fraction of the malignancies,” they wrote. “Given the morbidity and mortality associated with VTEs in patients with cancer, our study adds further support to calls for prospective trials of cisplatin-based chemotherapy administered with prophylactic anticoagulation,” they noted.

In efforts to personalize therapy, studies of genetic susceptibility loci for cisplatin-associated VTEs should also be considered.

Abstract

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