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

Abstract and Introduction

Study Objective: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide.
Design: Retrospective analysis of a randomized phase II trial.
Setting: National Institutes of Health clinical research center.
Patients: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer.
Intervention: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression.
Measurements and Main Results: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025).
Conclusion: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.

Thalidomide was withdrawn from clinical use 40 years ago when it was discovered to be teratogenic. However, it was subsequently shown to have activity in the treatment of leprosy and has been used routinely for the disease. Preclinical investigations have continued with this compound, and it was found to inhibit angiogenesis in vitro.[1,2] Because of this development, thalidomide has now returned to the clinical arena as an experimental treatment for various malignancies, including multiple myeloma,[3] gliomas,[4] Kaposi's sarcoma,[5] renal cell and colon carcinoma, advanced breast cancer, and myelodysplastic syndromes.[6] However, reports have begun to appear about an apparently new complication of thalidomide therapy in some of these patients, venous thromboembolism (VTE).[7,8,9,10,11]

According to these reports, most instances of VTE have occurred in patients with multiple myeloma treated with thalidomide plus other agents.[7,8,9,10,11] In several series, approximately 28% of the patients developed thrombosis.[7,8,9,10,11] However, 23% of a group of patients treated for renal cell carcinoma with thalidomide alone recently were reported to have developed VTE,[12] and thalidomide also has been implicated in the occurrence of VTE in patients with lupus erythematosus and antiphospholipid antibodies.[13]

We recently began a randomized trial of docetaxel with or without thalidomide to treat patients with androgen-independent prostate cancer.[14] In an earlier trial of thalidomide 200 mg/day administered alone in patients with this disease, we observed a 3% occurrence of VTE.[15] However, with the later addition of docetaxel, more instances of thrombosis were observed.[14]


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