Summary
Purpose: To evaluate the impact of flutamide on survival of patients with unresectable pancreatic cancer. Methods: This single institution, randomized, double-blind, placebo controlled study compared flutamide in the dose of 250 mg three times daily (n = 23) versus placebo (n = 23) in patients with histologically proven, previously untreated unresectable pancreatic adenocarcinoma. The primary end point was overall survival; secondary endpoints included 6-month and 1-year survival rates, performance status and response rate. Results: Both the groups were well matched with regards to demographic, disease related and treatment variables. This small sample sized study, failed to demonstrate a dramatic effect on survival with the use of flutamide. Median overall survival was 151 days with the use of flutamide as compared to 136 with placebo (p = 0.51). The 6-month survival rate was 39.13% in both arms of study and 1-year survival was 4.35% versus 13.04% for the flutamide group. There was no statistically significant difference in time to deterioration of performance status (flutamide 90 days versus placebo 68 days, p = 0.59) and all patients died as a result of tumor progression. Conclusions: Anti-androgen drug flutamide in the dose of 250 mg three times daily does not appear to prolong overall survival in unresectable pancreatic cancer.
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Corbishley TP, Iqbal MJ, Wilkinson ML, Williams R: Androgen receptor in human normal and malignant pancreatic tissue and cell lines. Cancer 57: 1992–1995, 1986
Greenway B, Duke D, Pym B, Iqbal MJ, Johnson PJ, Williams R: The control of human pancreatic adenocarcinoma xenografts in nude mice by hormone therapy. Br J Surg 69: 595–597, 1982
Greenway BA: Effect of flutamide on survival in patients with pancreatic cancer: results of a prospective, randomised, double blind, placebo controlled trial. Br Med J 316: 1935–1938, 1998
Wasan HS: Effect of flutamide on survival in patients with pancreatic cancer. No recommendations can be made. Br Med J 318: 327–328, 1999
Tonnesen K, Kamp-Jensen M: Antiestrogen therapy in pancreatic carcinoma: A preliminary report. Eur J Surg Oncol 12: 69–70, 1986
Wong A, Chan A, Arthur K: Tamoxifen therapy in unresectable adenocarcinoma of the pancreas. Cancer Treat Rep 71: 749–750, 1987
Keating JJ, Johnson PJ, Cochrane AM, Gazzard BG, Krasner N, Smith PM, Trewby PN, Wheeler P, Wilkinson SP, Williams R: A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma. Br J Cancer 60: 789–792, 1989
Bakkevold KE, Pettersen A, Arnesjo B, Espehaug B: Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and the papilla of Vater. Br J Surg 77: 725–730, 1990
Taylor OM, Benson EA, McMahon MJ: Clinical trial of tamoxifen in patients with irresectable pancreatic adenocarcinoma. The Yorkshire Gastrointestinal Tumour Group. Br J Surg 80: 384–386, 1993
Greenway BA: Androgen receptor-blocking agents: potential role in pancreatic cancer. Drugs Aging 17: 161–163, 2000
Sharma JJ, Razvillas B, Stephens CD, Hilsenbeck SG, Sharma A, Rothenberg ML: Phase II study of flutamide as second line chemotherapy in patients with advanced pancreatic cancer. Invest New Drugs 15: 361–364, 1997
Corrie P, Mayer A, Shaw J, D’Ath S, Blagden S, Blesing C, Price P, Warner N: Phase II study to evaluate combining gemcitabine with flutamide in advanced pancreatic cancer patients. Br J Cancer 87: 716–719, 2002
Yamashita J, Abe M, Ogawa M: Endocrine therapy in pancreatic carcinoma. Oncology 55: 17–22, 1998
Targarona EM, Pons MD, Gonzalez G, Boix L, Marco V, Marco C: Is exocrine pancreatic cancer a hormone-dependent tumor? A study of the existence of sex hormone receptors in normal and neoplastic pancreas. Hepatogastroenterology 38: 165–169, 1991
Taylor OM, Teasdale J, Cowen PN, McMahon MJ, Benson EA: Classical oestrogen receptor is not detectable in pancreatic adenocarcinoma. Br J Cancer 66: 503–506, 1992
Pettersen A, Lea O, Bakkevold K, Arnesjo B: Progress in pancreatic oestrogen receptors. Eur J Surg Oncol 12: 321–324, 1986
Andren-Sandberg A: Androgen influence on exocrine pancreatic cancer. Int J Pancreatol 4: 363–369, 1989
Townsend CM Jr, Singh P, Thompson JC: Gastrointestinal hormones and gastrointestinal and pancreatic carcinomas. Gastroenterology 91: 1002–1006, 1986
Wittliff JL: Steroid-hormone receptors in breast cancer. Cancer 53: 630–643, 1984
Greenway B, Iqbal MJ, Johnson PJ, Williams R: Low serum testosterone concentrations in patients with carcinoma of the pancreas. Br Med J 286: 93–95, 1983
Robles-Diaz G, Diaz-Sanchez V, Mendez JP, Altamirano A, Wolpert E: Low serum testosterone/dihydrotestosterone ratio in patients with pancreatic carcinoma. Pancreas 2: 684–687, 1987
Fyssas I, Syrigos KN, Konstandoulakis MM, Papadopoulos S, Milingos N, Anapliotou M, Waxman J, Golematis BC: Sex hormone levels in the serum of patients with pancreatic adenocarcinoma. Horm Metab Res 29: 115–118, 1997
Todd BD: Pancreatic carcinoma and low serum testosterone; a correlation secondary to cancer cachexia? Eur J Surg Oncol 14: 199–202, 1988
Andren-Sandberg A: Peptide hormone influence on exocrine pancreatic cancer. Eur J Surg Oncol 15: 236–241, 1989
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Negi, S.S., Agarwal, A. & Chaudhary, A. Flutamide in unresectable pancreatic adenocarcinoma: A randomized, double-blind, placebo-controlled trial. Invest New Drugs 24, 189–194 (2006). https://doi.org/10.1007/s10637-005-3536-2
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DOI: https://doi.org/10.1007/s10637-005-3536-2