Anticoagulants, survival, and advanced prostate cancer

At the Genitourinary Cancers Symposium a week ago there was a poster on a potential association between the use of blood thinners (i.e., the anticoagulants warfarin and low molecular weight heparin) by men with metastatic, castration-resistant prostate cancer (mCRPC) who had received docetaxel-based chemotherapy and an increase in overall survival benefit.

Here is a link to the abstract of the original poster by Platz et al. and here is another link to a HealthDay commentary on that poster that has just appeared on the web site of U.S. News and World Report. Let us be clear that the poster reported data from a retrospective cohort analysis. It was not a prospective clinical trial. Most of the men in the cohort (218/247 or 88.3 percent) were not receiving anticoagulant therapy.

Now we don’t claim to be geniuses, but we are having a hard time understanding why people seem to think that a 3.8-month median overall survival benefit might not be seen in the small sub-cohort of men who were being treated with docetaxel-based chemotherapy for metastatic prostate cancer and who were also receiving a blood thinner.

Let’s remember that all these men would have been receiving long-term androgen deprivation therapy (ADT) of some type or another; they would also have remained on ADT during and after their chemotherapy. ADT is associated with a risk for cardiovascular and other metabolic side effects. The use of anticoagulants like warfarin and low molecular weight heparin may well have helped some patients to avoid serious side effects of ADT. There were only 29/247 men in this retrospective study cohort who were taking anticoagulants (as opposed to the 218 who were not). Thus, it might only have taken a significant delay in the time of death for a couple of these patients to lead to a significant change in the median overall survival of the group of 29 patients.

Now we would certainly agree that these data do not, as yet, suggest that every man who is getting chemotherapy for advanced prostate cancer should get an anticoagulant. However, it does make one wonder whether every man who is on long-term ADT (particularly with an LHRH agonist) might want to discuss the possible benefits (and risks) of anticoagulant therapy with his doctors. It also raises the question of the value of a randomized, placebo-controlled pilot study to examine the benefit of anticoagulant therapy in men who are on long-term ADT (with and without additional, docetaxel-based chemotherapy).

As is carefully pointed out by Mann in her HealthDay commentary, based on the comments from one oncologist she consulted, “this is not the first time that blood thinners, including aspirin (which was not included in the new study), have been linked to improved survival for men with prostate cancer.” However, the use of anticoagulants in men receiving chemotherapy needs to be approached with great caution because of a potential risk for venous thromboembolism — blood clots deep in the leg veins. On the other hand, modern oral antcoagulant therapy, using drugs like clopidogrel (Plavix), is known to be relatively  (although we are not aware of data on the safety profile of such drugs if combined with LHRH agonist therapy or with docetaxel-based chemotherapy).

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