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

doi:10.1111/j.1464-410X.2007.06763.x

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 journal › Article › peer-review

39 Scopus citations

Abstract

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 language	English
Pages (from-to)	1047-1055
Number of pages	9
Journal	BJU International
Volume	99
Issue number	5
DOIs	https://doi.org/10.1111/j.1464-410X.2007.06763.x
State	Published - May 2007
Externally published	Yes

Keywords

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

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Figg, W. D., Li, H., Sissung, T., Retter, A., Wu, S., Gulley, J. L., Arlen, P., Wright, J. J., Parnes, H., Fedenko, K., Latham, L., Steinberg, S. M., Jones, E., Chen, C., & Dahut, W. (2007). Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer. BJU International, 99(5), 1047-1055. https://doi.org/10.1111/j.1464-410X.2007.06763.x

@article{5b51937fbf494a8085edb175fc3998bf,

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

abstract = "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.",

keywords = "CYP1B1, Cancer, Clinical, Cytochrome P450, Drug development, Oncology, PC3 cells, Pharmacogenetics, Phase II, Taxanes, Xenografts",

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

year = "2007",

month = may,

doi = "10.1111/j.1464-410X.2007.06763.x",

language = "English",

volume = "99",

pages = "1047--1055",

journal = "BJU International",

issn = "1464-4096",

number = "5",

}

Figg, WD, Li, H, Sissung, T, Retter, A, Wu, S, Gulley, JL, Arlen, P, Wright, JJ, Parnes, H, Fedenko, K, Latham, L, Steinberg, SM, Jones, E, Chen, C & Dahut, W 2007, 'Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer', BJU International, vol. 99, no. 5, pp. 1047-1055. https://doi.org/10.1111/j.1464-410X.2007.06763.x

TY - JOUR

T1 - Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide combination in androgen-independent prostate cancer

AU - Figg, William D.

AU - Li, Haiqing

AU - Sissung, Tristan

AU - Retter, Avi

AU - Wu, Shenhong

AU - Gulley, James L.

AU - Arlen, Phil

AU - Wright, John J.

AU - Parnes, Howard

AU - Fedenko, Kathy

AU - Latham, Lea

AU - Steinberg, Seth M.

AU - Jones, Elizabeth

AU - Chen, Clara

AU - Dahut, William

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

KW - CYP1B1

KW - Cancer

KW - Clinical

KW - Cytochrome P450

KW - Drug development

KW - Oncology

KW - PC3 cells

KW - Pharmacogenetics

KW - Phase II

KW - Taxanes

KW - Xenografts

UR - http://www.scopus.com/inward/record.url?scp=34247111244&partnerID=8YFLogxK

U2 - 10.1111/j.1464-410X.2007.06763.x

DO - 10.1111/j.1464-410X.2007.06763.x

M3 - Article

C2 - 17437439

AN - SCOPUS:34247111244

SN - 1464-4096

VL - 99

SP - 1047

EP - 1055

JO - BJU International

JF - BJU International

IS - 5

ER -

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

Abstract

Keywords

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