This article is more than 5 years old. Information may no longer be current.
Cisplatin increased VTE risk in patients with advanced solid tumors
Click Here to Manage Email Alerts
Certain patients with solid tumors who received cisplatin-based regimens were nearly 70% more likely to experience venous thromboembolism than patients who did not receive the drug, according to results of a meta-analysis.
Matthew D. Galsky, MD, director of genitourinary medical oncology at The Tisch Cancer Institute at Mount Sinai Medical Center, and colleagues analyzed phase 2 and phase 3 randomized controlled trials published in PubMed to assess associations between VTE risk and cisplatin-based chemotherapy. Studies that compared cisplatin-based regimens and non-cisplatin-based regimens in patients with solid tumors were included. The researchers extracted data for all-grade VTEs and graded study quality based on Jadad scores.
Articles published from 1990 to 2010 were eligible for analysis. The study included 38 randomized controlled trials that involved a combined 8,216 patients with various advanced solid tumors.
VTEs occurred at an incident rate of 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 chemotherapy.
The risk for VTEs was significantly increased in patients who received cisplatin (RR=1.67; 95% CI, 1.25-2.23).
“The primary message is that cisplatin is associated with an excess risk of venous thromboembolic disease in patients with advanced cancer compared with other chemotherapies,” Galsky told HemOnc Today. “This may be considered when selecting chemotherapy regimens in patients with an extensive history of venous thromboembolic disease, and clinicians may want to be extra vigilant in evaluating signs or symptoms of venous thromboembolic disease in patients receiving cisplatin-based regimens.”
Cisplatin is a used in several chemotherapy regimens, many of which are potentially curative, Galsky said.
“The benefits of cisplatin-based therapy still outweigh these risks for the vast majority of patients,” he said. “In addition, whether prophylactic anticoagulation should be considered in patients being treated with cisplatin-based regimens can only be answered by a prospective randomized clinical trial.”
Patients who received the drug at a dose of >30 mg/m2 on a weekly basis carried the highest VTE risk (RR=2.71; 95% CI, 1.17-6.30), according to an exploratory subgroup analysis.
Patients in trials from 2000 to 2010 also had an elevated VTE risk (RR=1.72; 95% CI, 1.27-2.34).
“The relative risk of venous thromboembolic disease is the key data point,” Galsky said. “The incidence of venous thromboembolic disease in our analysis was relatively low — much lower than in retrospective series. This is likely related to a ‘fitter’ group of clinical trial participants involved in this analysis and the fact that the rate of venous thromboembolic disease was not a primary endpoint of these studies and, as a result, was likely underreported.”
Perspective
Back to TopChristy Samaras, DO
Compared with the general population, patients with neoplastic disease have a four-fold or greater risk of developing venous thromboembolic events (VTE) or pulmonary emboli. Those cancer patients who receive chemotherapy and/or are in the post-operative setting and experience a VTE have at least twice the risk of dying within the first 6 months of their initial hospitalization compared with those who do not experience a VTE. Thus, preventing VTE in the ambulatory cancer patient is of major importance in their overall care plan.
Many factors contribute to the risk of cancer-related VTE: tumor type (the greatest risk is associated with brain tumors and adenocarcinomas of the stomach, pancreas, lung or ovary), disease stage, patient comorbidities and additional treatment-related factors. The increased risk of VTE with certain chemotherapeutic agents and supportive care agents (erythropoeitin-stimulating agents) is well recognized. Recommendations have been developed for VTE thromboprophylaxis in ambulatory cancer patients receiving regimens that include hormonal therapies, angiogenesis inhibitors, thalidomide and lenalidomide. However, there are no guidelines for several other chemotherapy regimens with thrombogenic potential. In particular, several case reports and retrospective analyses have reported an increased risk of VTE in patients receiving cisplatin-containing regimens, yet no clear consensus exists with regard to thromboprophylaxis in these patients.
In this study, Seng and colleagues conducted a systematic literature review and meta-analysis of randomized controlled trials (RCTs) to evaluate the incidence and risk of VTE in patients receiving a cisplatin-based chemotherapy regimen, irrespective of underlying cancer type. In 8,216 patients across 38 RCTs, the incidence of VTE was increased in patients who received cisplatin-based therapy compared with patients treated with non-platinum–containing regimens (1.92%, 95% CI, 1.07-2.76 vs. 0.79%, 95% CI, 0.45-1.13). The relative risk for VTE was greater in patients who received cisplatin-based therapies, with the greatest risk seen in those who received higher doses of drug.
This meta-analysis included studies published in the time period of Jan. 1, 1990, through Dec. 31, 2010. Interestingly, in subgroup analysis based on publication year, the incidence and relative risk of VTE in patients who received cisplatin was greater in the 28 trials published from 2000 to 2010 compared with trials published prior to 2000, though this difference did not reach statistical significance. The authors hypothesized that the apparent difference may reflect increased diagnosis of incidental VTE due to expanding use of high resolution CT.
The limitation of this report is that it is a meta-analysis of an incidental finding. That is, assessment for VTE occurrence was a primary endpoint in only one of the trials included in the analysis. Indeed, 13 trials in the meta-analysis reported no VTE in either the treatment or control arms. Furthermore, there was great heterogeneity across trials with regard to dose and schedule of cisplatin administration.
Cancer-associated VTE remains an important problem. How the additional risks of VTE associated with chemotherapy interfaces with those due to the underlying neoplasm and intrinsic to a specific patient is uncertain, making the assessment of which patients will benefit most from prophylaxis challenging. This meta-analysis adds to the expanding body of literature regarding VTE risk associated with cisplatin. However, several questions remain unanswered. For example, are regimens that include higher dose boluses of cisplatin (vs. lower dose/infusional protocols), with their increased emetic potential and risk of dehydration, associated with higher risk of VTE? Does the effect of cisplatin on the patient’s performance status contribute to increased risk of VTE?
Further studies that include VTE assessment as a primary endpoint and assess risk-benefit of thromboprophylaxis as it pertains to cost effectiveness are needed. As data from such studies accumulates, better risk stratification models and guidelines will be available to clinicians, allowing them to rationally determine the utility of primary thromboprophylaxis in their patients who receive cisplatin.
Collapse
Click Here to Manage Email Alerts