Cisplatin Linked to Significantly Increased Risk of Venous Thromboembolism


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Our study adds further support to calls for prospective trials of cisplatin-based chemotherapy administered with prophylactic anticoagulation.

Patients with advanced solid tumors treated with cisplatin-based chemotherapy had a significantly increased risk of venous thromboembolic events, according to a meta-analysis of 38 randomized phase II and III trials evaluating cisplatin-based vs non–cisplatin-based chemotherapy. The trials involved a total of 8,216 patients with various solid tumors.

The incidence of venous thromboembolic events was 1.92% (95% CI = 1.07–2.76) in patients treated with cisplatin-based chemotherapy and 0.79% (95% CI = 0.45–1.13) in patients treated with non–cisplatin-based regimens, Sonia Seng, MD, of Southcoast Centers for Cancer Care, Fairhaven, Massachusetts, and co-investigators reported in the Journal of Clinical Oncology.1 Patients given cisplatin-based chemotherapy had a significantly increased risk of venous thromboembolic events (relative risk [RR] = 1.67; 95% CI = 1.25–2.23; P = .01).

The authors noted that the finding of a 1.67-fold increase in the risk of venous thromboembolic events with cisplatin, “should be viewed in the context of a recent meta-analysis suggesting a 1.33-fold increased risk of [such events] with bevacizumab [Avastin], an antivascular endothelial growth factor receptor antibody, which has been used for decades less frequently than cisplatin to treat a fraction of the malignancies.”

Subgroup Analysis

Exploratory subgroup analysis showed that the highest relative risk of venous thromboembolic events was among patients who received a weekly equivalent cisplatin dose > 30 mg/m2 (2.71; 95% CI = 1.17–6.30; P = .02). “Although the lack of a linear increase in RR with increasing dose does not support a dose-response relationship, a threshold effect cannot be ruled out,” the researchers wrote.

To explore whether the excess risk or venous thromboembolic events was unique to cisplatin or common to all platinum agents, patients in the control arm were categorized according to whether their drug regimen included another platinum agent such as carboplatin or oxaliplatin. “Interestingly, the effect size was greater in the analysis comparing cisplatin-based chemotherapy with regimens containing other platinum agents (RR = 1.96; 95% CI = 1.38–2.78; P = .01) vs the analysis comparing cisplatin-based chemotherapy with nonplatinum regimens (RR = 1.22; 95% CI = 0.74–2.00; P = .43); however, there was no significant difference between these subgroups,” the investigators stated.

The incidence of venous thromboembolic events was highest among patients with gastric/esophageal cancer, followed by patients with pancreatic and small cell lung cancer, although the differences among tumor types were not statistically significant. “Given the morbidity and mortality associated with [venous thromboembolic events] in patients with cancer, our study adds further support to calls for prospective trials of cisplatin-based chemotherapy administered with prophylactic anticoagulation,” the authors concluded. ■

Reference

1. Seng S, Liu Z, Chiu SK, et al: Risk of venous thromboembolism in patients with cancer treated with cisplatin: A systematic review and meta-analysis. J Clin Oncol 30:4416-4426, 2012.



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