© 1994 by Oxford University Press
Journal of the National Cancer Institute, Vol. 86, No. 3, 222-227,
February 2, 1994
© 1994 Oxford University Press
Surprising Activity of Flutamide Withdrawal, When Combined With Aminoglutethimide, in Treatment of "Hormone-Refractory" Prostate Cancer
Clinical Pharmacology Branch
Biostatistics and Data Management Section
(Surgery Branch), Division of Cancer Treatment, National Cancer Institute, Bethesda, Md.
*Correspondence to: Oliver Sartor, M.D., Lousiana State University Medical Center, Hematology/Oncology. P.O. Box 33932, Shreveport, LA 71130.
BACKGROOUND: The best treatment for patients with "hormone-refractory" metastatic prostate cancer is unclear, particularly in patients for whom suramin and hydrocortisone have failed.
PURPOSE: We investigated a combination of flutamide withdrawal and aminoglutethimide in suramin-and hydrocortisone-pretreated patients with "Hormone-refractory" prostate cancer.
METHODS: Twenty-nine patients with metastatic prostate cancer were treated with simultaneous flutamide withdrawal and aminoglutethimide (250 mg given orally four times daily). All patients were taking flutamide at the time of entry, and previous treatments with medical or surgical castration, flutamide, suramin, and hydrocortisone had failed in all of these patients. Because of suramin-induced adrenal insufficiency, all patients had previously received, and continued to receive, physiological doses of hydrocortisone. Treatment of all nonsurgically castrated patients had previously failed; however, these patients continued to receive depot leuprolide. Results: In 14 (48%) of 29 patients, the prostate-specific antigen (PSA) decreased by more than 80% for 4 or more weeks. Improvements in anemia, thrombocytopenia, soft-tissue masses, bone scans, and symptoms were also noted. Factors associated with response included prolonged flutamide pretreatment, a markedly elevated pretreatment PSA, and the absence of soft-tissue disease.
CONCLUSIONS: Flutamide withdrawal, when combined with the simultaneous administration of aminoglutethimide, is a therapeutically active approach in patients with "hormone-refractory" prostate cancer. Implications: On the basis of these and additional data, we hypothesize that prolonged exposure to flutamide results in the selective proliferation of cancer cells containing a mutant androgen receptor that aberrantly recognizes flutamide metabolites and nonandrogenic steroids as androgenic stimuli. [J Natl Cancer Inst 86:222–227, 1994]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. J. Ryan, S. Halabi, S.-S. Ou, N. J. Vogelzang, P. Kantoff, E. J. Small, and for the Cancer and Leukemia Group B Adrenal Androgen Levels as Predictors of Outcome in Prostate Cancer Patients Treated with Ketoconazole Plus Antiandrogen Withdrawal: Results from a Cancer and Leukemia Group B Study Clin. Cancer Res., April 1, 2007; 13(7): 2030 - 2037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Heinlein and C. Chang Androgen Receptor in Prostate Cancer Endocr. Rev., April 1, 2004; 25(2): 276 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Small, S. Halabi, N. A. Dawson, W. M. Stadler, B. I. Rini, J. Picus, P. Gable, F. M. Torti, E. Kaplan, and N. J. Vogelzang Antiandrogen Withdrawal Alone or in Combination With Ketoconazole in Androgen-Independent Prostate Cancer Patients: A Phase III Trial (CALGB 9583) J. Clin. Oncol., March 15, 2004; 22(6): 1025 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-Y. Chang, P. J. Walther, and D. P. McDonnell Glucocorticoids Manifest Androgenic Activity in a Cell Line Derived from a Metastatic Prostate Cancer Cancer Res., December 1, 2001; 61(24): 8712 - 8717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Long, D. N. Grigoryev, I. P. Nnane, Y. Liu, Y.-Z. Ling, and A. M. Brodie Antiandrogenic Effects of Novel Androgen Synthesis Inhibitors on Hormone-dependent Prostate Cancer Cancer Res., December 1, 2000; 60(23): 6630 - 6640. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Auclerc, E. C. Antoine, F. Cajfinger, A. Brunet-Pommeyrol, C. Agazia, and D. Khayat Management of Advanced Prostate Cancer Oncologist, February 1, 2000; 5(1): 36 - 44. [Abstract] [Full Text]
|
|
|
|
|
|
M.-E. Taplin, G. J. Bubley, Y.-J. Ko, E. J. Small, M. Upton, B. Rajeshkumar, and S. P. Balk Selection for Androgen Receptor Mutations in Prostate Cancers Treated with Androgen Antagonist Cancer Res., June 1, 1999; 59(11): 2511 - 2515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. I. Scher, W. M. K. Kelly, Z.-F. Zhang, P. Ouyang, M. Sun, M. Schwartz, C. Ding, W. Wang, I. D. Horak, and A. B. Kremer Post-therapy Serum Prostate-Specific Antigen Level and Survival in Patients With Androgen-Independent Prostate Cancer J Natl Cancer Inst, February 3, 1999; 91(3): 244 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-a. Tan, Y. Sharief, K. G. Hamil, C. W. Gregory, D.-Y. Zang, M. Sar, P. H. Gumerlock, R. W. deVere White, T. G. Pretlow, S. E. Harris, et al. Dehydroepiandrosterone Activates Mutant Androgen Receptors Expressed in the Androgen-Dependent Human Prostate Cancer Xenograft CWR22 and LNCaP Cells Mol. Endocrinol., April 1, 1997; 11(4): 450 - 459. [Abstract] [Full Text]
|
|
|
|
 |
|
 W. D. Figg, M. Middleman, O. Sartor, S. P. Balk, G. J. Bubley, and T. D. Shuster Mutated Androgen Receptors of Prostate-Cancer Cells N. Engl. J. Med., October 12, 1995; 333(15): 1010 - 1011. [Full Text]
|
|
|
|
 |
|
 W. D. Figg, A. Thibault, A. O. Sartor, D. Mays, D. Headlee, K. A. Calis, and M. R. Cooper Hypothyroidism Associated With Aminoglutethimide in Patients With Prostate Cancer Arch Intern Med, May 9, 1994; 154(9): 1023 - 1025. [Abstract] [PDF]
|
|