Increased Frequency of Venous Thromboembolism With the Combination of Docetaxel and Thalidomide in Patients With Metastatic Androgen-Independent Prostate Cancer

McDonald K. Horne III, M.D., William D. Figg, Pharm.D., FCCP, Phil Arlen, M.D., James Gulley, M.D., Ph.D., Catherine Parker, R.N., Nehal Lakhani, M.D., Howard Parnes, M.D., William L. Dahut, M.D.


Pharmacotherapy. 2003;23(3) 

In This Article


Seventy men, aged 50-80 years, were observed under treatment on protocol for 2-12 months (mean ± SD duration 5.1 ± 2.7 mo). Fifty-three of these patients participated in an earlier trial.[14]

Twenty-three of the 70 patients received docetaxel alone. None of the 23 developed clinically evident VTE. Also, none of the 23 had experienced a VTE event before the study, and only one of them took any anticoagulant (warfarin for an arrhythmia) while receiving docetaxel. There were no demographic differences among the participants in this treatment arm.

The remaining 47 patients received docetaxel plus thalidomide. Two of them were taking warfarin when they entered the study -- one because of an arrhythmia, the other because he had experienced a VTE within the past year. The latter patient developed recurrent VTE after 3.5 months of receiving docetaxel and thalidomide. Three other men who received the drug combination also had experienced VTE before the start of this study. Two of these patients, whose thrombotic episodes had been 8 and 9 years earlier, developed recurrent VTE after 2 and 8 months, respectively, of docetaxel plus thalidomide. In addition, six men developed first-time VTE after receiving thalidomide for 3 weeks, 4 weeks, 7 weeks, 2 months, 5 months, and 9 months.

If all 47 men in the thalidomide plus docetaxel arm are considered, the frequency of VTE (9/47 [19%]) is significantly greater than that in the docetaxel alone arm (0/23; Fisher exact p= 0.0254). If all three men with recurrent VTE are excluded, the increased frequency of VTE in the thalidomide plus docetaxel arm of the study (6/44 [14%]) is only marginally significant (p=0.0634). However, if we exclude only the patient whose earlier VTE occurred within the past 8 years, the significance of the increased frequency of thrombosis in this group (8/46 [17%]) is greater (p=0.03).

Plasma samples were drawn from 21 men in the week before starting docetaxel plus thalidomide and again 1-2 months after the start of treatment. None of these patients was taking any anticoagulant during this time. Protein C, protein S, antithrombin, factor VIII, activated protein C resistance, and thrombin-antithrombin complexes were measured in each sample. There were no statistically significant differences in antithrombin, factor VIII, or thrombin-antithrombin levels before and after starting docetaxel plus thalidomide (p=0.56-0.79). The differences in protein S and activated protein C resistance also showed only nonsignificant trends (p=0.053-0.068). However, we found a statistically significant fall in protein C after the patients began treatment (p=0.003). Seventeen of 21 patients developed lower protein C levels, ranging from a drop of 0.10 to 0.91 U/ml, but only one patient developed a protein C level (0.42 U/ml) that was below the laboratory's normal range of 0.70-1.5 U/ml. Because suitable samples were available from only five of the nine patients who developed VTE, no meaningful comparisons were possible between the men who did and did not develop thrombosis.

Plasma samples were drawn from 10 men the week before starting docetaxel alone and again 1-2 months after starting treatment. None of these patients was taking any anticoagulant during this time. The samples were tested for protein C and S levels. There were no significant changes in either protein (protein C, p=0.30; protein S, p=0.08).


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.