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

BJU Int. 2007 May;99(5):1047-55. doi: 10.1111/j.1464-410X.2007.06763.x.


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Androgens / metabolism*
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 Enzyme System / genetics
  • Docetaxel
  • Estramustine / administration & dosage
  • Genotype
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality
  • Survival Analysis
  • Taxoids / administration & dosage
  • Thalidomide / administration & dosage
  • Treatment Outcome


  • Androgens
  • Taxoids
  • Docetaxel
  • Estramustine
  • Thalidomide
  • Cytochrome P-450 Enzyme System
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cyp1b1 protein, mouse
  • Cytochrome P-450 CYP1B1