Drugs Xagena
Six Canadian cases of aortic thrombosis have been reported in cancer patients after initiation of treatment with Cisplatin, in addition to 15 published international cases.
In many of these patients, the condition stabilized or resolved after initiation of anticoagulation therapy or surgery.
Early detection and management of aortic thrombosis increases the chances of a favourable outcome.
Cisplatin, a Platinum agent, is a DNA-modifying anticancer drug that has been marketed in Canada since 1979. It is indicated for the treatment of genitourinary cancers including cancers of the testis, bladder and ovary.
Aortic thrombosis is a rare and potentially life-threatening disorder characterized by the formation of a clot in the aorta. It rarely occurs spontaneously in such large vessels without the presence of atherosclerotic plaques.
Aortic thrombosis may be related to concomitant hereditary or acquired hypercoagulable states, as well as to factors that promote clot formation ( e.g., cancer, pregnancy, recent surgery, trauma, immobility, use of certain medications or substances, sepsis, polycythemia, autoimmune disease, inflammation of the blood vessels, smoking, etc. ).
As of April 30, 2014, 6 Canadian cases of aortic thrombosis in cancer patients after treatment initiation with Cisplatin were reported to Health Canada, including 5 published cases. The most recent Canadian case occurred in 2011.
Of the 6 Canadian cases, 5 indicated that the patient was treated with anticoagulants and one required surgery ( thrombectomy of the aorta and aortobifemoral grafts in one case ). In 3 cases, the thrombus was detected after the last dose of Cisplatin.
The status of Cisplatin treatment continuation is unknown for the remaining cases. Potential confounding factors for aortic thrombosis in these cases included a higher coagulation state associated with the underlying malignancy and other known predisposing factors such as smoking ( reported in 4 cases ), obesity ( noted in one case ), and previous history of vascular disease ( transient ischemic attacks noted in one case ).
Fifteen additional international cases reporting the occurrence of aortic thrombosis after initiation of treatment with Cisplatin were identified in the literature from 13 publications.
The product monographs for Cisplatin do not list aortic thrombosis. However, they indicate that cases of clinically heterogeneous vascular toxicities coincident with the use of Cisplatin in combination with other antineoplastic agents have been reported rarely. These events may include myocardial infarction, cerebrovascular accident, thrombotic microangiopathy ( hemolytic uremic syndrome ), and cerebral arteritis. The exact mechanism for the occurrence of vascular toxicities with Cisplatin is unclear. ( Xagena )
Source: Health Canada, 2014
XagenaMedicine_2014
