Summary
Retinoids have shown a tumor growth inhibition and a synergistic activity with hormonal manipulations in human breast cancer cell lines and rat mammary carcinoma. To investigate the potential usefulness of this synergistic activity in human breast cancer, 33 postmenopausal patients with advanced disease were treated with the combination of tamoxifen (10 mg p.o. three times a day) and retinyl acetate (300 000 IU p.o. daily). Out of 31 evaluable patients, 3 achieved complete response, 9 partial response (overall response rate: 38.5%, 95% confidence interval=21%–56%) and 16 (52%) showed no change. The median duration of response was 11.5 months (range: 3–19+months), while the 2-year overall survival rate for the entire group of patients was 63%. Toxicity was generally mild, hot flushes, nausea (and/or vomiting), headache and cutaneous itching being the most frequent side-effects. Only 1 patient discontinued treatment for severe toxicity. These preliminary results suggest that the combination of tamoxifen and high-dose retinyl acetate is a safe and effective regimen for breast cancer patients. However, the study design does not allow us to establish whether the very low rate of early disease progression we observed might be related to a possible synergistic effect between retinoids and antiestrogens or rather to the quite indolent disease of the patients who have been selected for entry into this trial.
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References
Boccardo F (1985) Clinical experience with tamoxifen as sole therapy in advanced breast cancer. Excerpta Med Curr Clin Pract Ser 31:170–178
Boccardo F, Cerruti G, De Menech R, Valenti G, Zanardi S (1987) Effects of retinol palmitate (RP) and hormonal manipulations on MXT transplantable mammary tumors. J Steroid Biochem 28[Suppl 1]:144S, D-007
Cassidy J, Lippman M, Lacroix A, Peck G (1982) Phase II trial of 13-cis-retinoic acid in metastatic breast cancer. Eur J Cancer Clin Oncol 18:925–928
Fontana JA (1987) Interaction of retinoids and tamoxifen on the inhibition of human mammary carcinoma cell proliferation. Exp Cell Biol 55:136–144
Gasparini G, Canobbio L, Galligioni E, Fassio T, Brema F, Crivellari D, Villalta D, Talamini R, Di Fronzo G, Monfardini S (1987) Sequential combination of tamoxifen and high-dose medroxiprogesterone acetate: therapeutic and endocrine effects in postmenopausal advanced breast cancer patients. Eur J Cancer Clin Oncol 23:1451–1459
Goodman GE, Alberts DS, Earnst DL, Meyskens FL (1983) Phase I trial of retinol in cancer patients. J Clin Oncol 1:394–399
Israel L, Hojji O, Grefft-Alami A (1985) Prospective randomized study of high dose vitamin A in 100 metastatic breast cancer patients. Significant advantage of vitamin A in postmenopausal patients. Proc Am Soc Clin Oncol c-221
Jordan VC (1986) Oestrogen and anti-oestrogen action: a hypothesis for the regulation of breast cancer cell replication. In: Cavalli F (ed) Endocrine therapy of breast cancer. Springer, Berlin Heidelberg New York pp, 41–50
Lippman ME, Kessler JF, Meyskens FL Jr (1987a) Retinoids as preventive and therapeutic anticancer agent (part I). Cancer Treat Rep 71:391–405
Lippman ME, Kessler JF, Meyskens FL Jr (1987b) Retinoids as preventive and therapeutic anticancer agents (part II). Cancer Treat Rep 71:493–515
Lotan R (1979) Different susceptibility of human melanoma and breast carcinoma cell lines to retinoic acid-induced growth inhibition. Cancer Res 39:1014–1019
Manni A (1988) Hormones and tumor biology in animal and in man. In: Pannuti F (ed) Advances in clinical oncology hormonotherapy: results and perspectives, vol 3. Edizioni Medico Scientifiche, Pavia, pp 29–39
McCormik DL, Metha RG, Thompson CA, Dinger M, Caldewell AC, Moon RC (1982) Enhanced inhibition of mammary carcinogenesis by combined tretment withN-(4-hydroxyphenyl)retinamide and ovariectomy. Cancer Res 42:508–512
McCormick DL, Sowel ZL, Thompson CA, Moon RC (1983) Inhibition by retinoids and ovariectomy of additional primary malignancies in rats following surgical removal of the first mammary cancer. Cancer 51:594–599
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer 47:207–214
Moon RC, McCormick DL, Metha RG (1983) Inhibition of carcinogenesis by retinoids. Cancer Res 43:2469
Mouridsen HT (1986) Endocrine treatment of advanced breast cancer. In: Cavalli F (ed) Endocrine therapy of breast cancer. Springer, Berlin Heidelberg pp, 79–90
O'Brian CA, Liskamo RM, Solomon DH, Weistein IB (1985) Inhibition of protein kinase C by tamoxifen. Cancer Res 45:2462–2465
Ratko TA, Detrisac CJ, Dinger NM, Thomas CF, Kellof GJ, Moon RC (1989) Chemopreventive efficacy of combined retinoid and tamoxifen treatment following surgical excision of a primary mammary cancer in female rats. Cancer Res 49:4472–4476
Resasco M, Canobbio L, Trave F, Mazzoni A, Canti G, Boccardo F, Nicolin A (1988) Plasma retinol levels and side effects following high-dose retinyl acetate in breast cancer patients. Anticancer Res 8:1319–1324
Robustelli della Cuna G, Pavesi L, Preti P (1985) Tamoxifen/medroxyprogesterone acetate sequential treatment for advanced breast cancer. Excerpta Med Curr Clin Pract Ser 31:183–189
Tellman K, Bollag W (1988) Therapeutic effect of the arotinoid RO 15-0778 on chemically induced rat mammary carcinoma. Eur Cancer Clin Oncol 24:1205–1209
Welsch CW, De Hoog JV (1983) Retinoid feeding, hormone inhibition and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas. Cancer Res 43:585–591
Wetherall NT, Taylors CM (1986) The effects of retinoid treatment and antiestrogens on the growth of T 47 D human breast cancer cells. Eur J Cancer Clin Oncol 22:53–59
Zanardi S, De Menech R, Cerruti G, Valenti G, Boccardo F (1988) Control of the growth of experimental murine mammary tumors by retinoids and hormones or antihormones. In: Castagnetta L, Nenci I (eds) Biology and biochemistry of normal and cancer cell growth. Harwood Academic Publishers, Chur, Switzerland, pp 117–120.
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Boccardo, F., Canobbio, L., Resasco, M. et al. Phase II study of tamoxifen and high-dose retinyl acetate in patients with advanced breast cancer. J Cancer Res Clin Oncol 116, 503–506 (1990). https://doi.org/10.1007/BF01613002
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DOI: https://doi.org/10.1007/BF01613002