Calusterone (7β,17α-DimethyItestosterone) as Primary and Secondary Therapy of Advanced Breast Cancer

Abstract

The antitumor efficacy of calusterone, 200 mg/day by mouth, against objectively progressing advanced breast cancer was evaluated by the Cooperative Breast Cancer Group criteria in 117 women. In 41, calusterone was the first treatment for advanced breast cancer, in 49 it was given as secondary steroidal therapy, and in 27 it followed cytotoxic chemotherapy. Part of the study included comparison by the double-blind technique of calusterone in 23 women with Δ¹-testololactone, 1,000 mg/day by mouth, in 25 similar patients randomly distributed for site of most significant metastasis and for age with respect to the menopause. Calusterone produced objective regressions lasting an average of 9.8 months in 51% of patients in whom it was primary or secondary hormonal therapy, but in only 19% of patients with previous cytotoxic chemotherapy. In the last group, regressions lasted only 6 months. Calusterone was equally effective in women with or without visceral metastasis, in all age groups, and in castration failures. In the double-blind study, calusterone produced regressions in 52% and Δ¹-testololactone in 32% of patients. In the crossover, patients who had not responded to calusterone also failed to respond to Δ¹-testololactone, while 33% of Δ¹-testololactone failures or responders obtained regression on calusterone therapy. Calusterone is a weak androgen, and, like other 17α-alkylated steroids, produces nausea in 28 % of patients and BSP retention almost uniformly. There was no cholestatic jaundice or hepatocellular damage. Nausea was usually transient, but of sufficient severity in five patients to necessitate termination of therapy. Unlike other androgens, calusterone causes no rise in hematocrit, but a striking increase in the platelet count and a slight rise in the white blood cell count. By the rigorous criteria of the Cooperative Breast Cancer Group, calusterone is the most effective antitumor steroid thus far identified in a statistically adequate sample.

Combined High-Dose ▵¹-TestoloIactone with Low-Dose 5-Fluorouracil in the Treatment of Metastatic Breast Cancer

“…In contrast to the 32% regression rate obtained with the Upjohn tablets of AMestololactone, l,000/day,as primary hormonal therapy, the samepreparation produced only one regression in 12 previously treated women (8%) [12]. We thus confirm the claim of Segaloff et ai [18] that AMestololactone is a potent antitumor agent when used as primary therapy against advanced fe male breast cancer.…”

“…Subse quently, The Upjohn Co. prepared for us compressed tablets of AMestololactone with T50 of 4.5 to 8.5 min. When tested for antitumor efficacy against advanced breast cancer in women without previous hormonal or chemothera py, using a dose of 1,000 mg/day by mouth, the Upjohn preparation pro duced regressions in 8 of 25 women (32%) [12]. In this study, A'-testololactone was double-blinded against calusterone, 200 mg/day by mouth, which produced 12 regressions in 23 women (52%).…”

Androgen receptor signaling pathways as a target for breast cancer treatment

“…Subsequently, the use of testosterone propionate, the testosterone derivative fluoxymesterone and the steroid calusterone obtained promising results in terms of disease response and pain relief in patients with metastatic BC (MBC) whose hormone receptor status was unknown (Segaloff et al 1951, Kennedy 1958, Goldenberg 1964, Goldenberg et al 1973, Gordan et al 1973). More recently, Boni et al reported a significant therapeutic activity of testosterone propionate in a consecutive series of 53 patients with ER/PgR-positive MBC (Boni et al 2014).…”

Role of Androgens on MCF-7 Breast Cancer Cell Growth and on the Inhibitory Effect of Letrozole

“…In breast cancer cells, androgens, such as 5a-dihydrotestosterone and its precursors androstenedione and testosterone, have inhibitory effects (2-9), whereas estrogens, such estradiol, have mitogenic effects. In fact, testosterone propionate, fluoxymesterone, and calusterone were previously used in the adjuvant therapy of breast cancer in both premenopausal and postmenopausal women with an efficacy comparable to that achieved with other types of endocrine manipulations, such as tamoxifen (10)(11)(12)(13). The androgen receptor (AR) is present in 50% to 90% of breast tumors (14), and the AR levels are closely correlated with the content of estrogen receptor (ER) and progesterone receptor.…”