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Pre‐clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen‐independent prostate cancer
Author(s) -
Figg William D.,
Li Haiqing,
Sissung Tristan,
Retter Avi,
Wu Shenhong,
Gulley James L.,
Arlen Phil,
Wright John J.,
Parnes Howard,
Fedenko Kathy,
Latham Lea,
Steinberg Seth M.,
Jones Elizabeth,
Chen Clara,
Dahut William
Publication year - 2007
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2007.06763.x
Subject(s) - docetaxel , estramustine , medicine , thalidomide , prostate cancer , combination therapy , oncology , urology , cancer , multiple myeloma , prostate disease
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 mm 3 . 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/m 2 ) 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.