Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer

William D. Figg*, Haiqing Li, Tristan Sissung, Avi Retter, Shenhong Wu, James L. Gulley, Phil Arlen, John J. Wright, Howard Parnes, Kathy Fedenko, Lea Latham, Seth M. Steinberg, Elizabeth Jones, Clara Chen, William Dahut

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


OBJECTIVE: To evaluate the combination of docetaxel plus estramustine (which prolongs survival in patients with androgen-independent prostate cancer, AIPC), and thalidomide (that also adds to docetaxel activity), both pre-clinically and clinically in AIPC. PATIENTS, MATERIALS AND METHODS: In the pre-clinical evaluation we injected PC3 cells subcutaneously into severely combined immunodeficient mice and started treatment after the tumour volume reached 50 mm3. We also evaluated the combination using luciferase-labelled PC3M-luc-C6 cells in nude mice. We enrolled 20 patients with metastatic progressive AIPC into a phase II clinical trial to evaluate this combination. Docetaxel (30 mg/m2) was administered every week, for 3 of 4 weeks. The dose of thalidomide was 200 mg/day and estramustine was given three times a day at 1, 2, 3, 8, 9, 10, 15, 16 and 17 days. RESULTS: In the mice, thalidomide with docetaxel plus estramustine reduced tumour volume by 88% at 17 days vs the control treatment (p = 0.001). The combination of docetaxel, estramustine and thalidomide nearly eradicated the signal from the luciferase-expressing PC3M cells in the metastasis model. Clinically, the progression-free time was 7.2 months with this combination; 18 of 20 patients had a decline of half or more in prostate-specific antigen level and two of 10 patients with soft-tissue lesions had a partial response on computed tomography. There were 24 grade 3 and two grade 4 complications associated with this combination. There was a statistically significant association between overall survival and the CYP1B1*3 genotype (P = 0.013). CONCLUSION: Docetaxel-based chemotherapy is now regarded as a standard regimen for metastatic AIPC. The combination of estramustine, docetaxel and thalidomide is an advantageous treatment in pre-clinical models of prostate cancer and is a safe, tolerable and active regimen in patients with AIPC.

Original languageEnglish
Pages (from-to)1047-1055
Number of pages9
JournalBJU International
Issue number5
StatePublished - May 2007
Externally publishedYes


  • CYP1B1
  • Cancer
  • Clinical
  • Cytochrome P450
  • Drug development
  • Oncology
  • PC3 cells
  • Pharmacogenetics
  • Phase II
  • Taxanes
  • Xenografts


Dive into the research topics of 'Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer'. Together they form a unique fingerprint.

Cite this