mepitiostane and Breast-Neoplasms

The results of adjuvant trials conducted from April, 1972 to August, 1978 showed that chemotherapy was more effective to premenopausal patients and endocrine therapy prolonged disease-free survival of postmenopausal patients compared with premenopausal ones. Preliminary analysis of randomized trial now on going suggests that endocrine therapy is best candidate for receptor-positive patients and chemotherapy for receptor-negative patients. Prognostic factors of primary breast cancer was discussed.

Topics: Androstanols; Breast Neoplasms; Combined Modality Therapy; Estrogen Antagonists; Female; Humans; Mitomycin; Mitomycins; Postoperative Period; Prognosis

A randomized controlled trial was performed to compare the therapeutic results of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA was given at three doses of 400 mg orally daily to 47 patients and produced objective responses in 19 cases (40.4%). An objective response was seen in 14 of the 40 control patients given MS at two doses of 10 mg orally daily (35.0%). Among patients with bone metastases, 6 of 19 (31.6%) for HD-MPA and 2 of 13 (15.4%) for MS showed objective responses. The other merits of HD-MPA suggested in the study were improvement in performance status, increase in appetite, and myeloprotective effect.

Topics: Adult; Androstanols; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Estrogen Antagonists; Female; Humans; Medroxyprogesterone; Medroxyprogesterone Acetate; Menopause; Middle Aged; Ovariectomy; Random Allocation

A randomized controlled trial was made to compare the therapeutic result of oral high-dose medroxyprogesterone acetate (HD-MPA) versus mepitiostane (MS) in the treatment of postmenopausal breast cancer. MPA (1200 mg) was given p.o., b.i.d. to 47 patients and produced objective response in 19 of them (40.4%). Objective response was seen in 14 of the 40 control patients given MS p.o., b.i.d. (35.0%). Among patients with bone metastases, 6/19 (31.6%) for HD-MPA and 2/23 (15.4%) for MS showed objective response. The other merits of HD-MPA suggested in the study were improvement in performance status, anabolic effect and myeloprotective effect.

Topics: Administration, Oral; Adult; Androstanols; Antineoplastic Agents; Breast Neoplasms; Capsules; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Humans; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged

Additive endocrine therapy of breast cancer was first initiated by androgen treatment through intramuscular administration which proved to be effective in about 25% of trial cases. It was followed by another trial of massive administration of estrogens mainly to patients of more than 60 years of age, and this showed a similar efficacy. Under these circumstances, additive endocrine therapy's position was established as a special therapy for advanced breast cancer. Breast cancer patients have a considerably longer period of progress after disease recurrence than in other types of cancer, so oral androgens were developed for treating recurrent breast cancer patients at home. However, the side effects of androgens (e.g., virilization, hepatic disorders) presented problems with Long-term administration. Since then more androgens with less side effects have been developed which have contributed to the remarkable progress of androgen therapy. On the other hand, recently an anti-estrogen was found which specifically antagonizes estrogen and has few side effects. Additive endocrine therapy's reputation has improved with the emergence of this anti-estrogen agent. Another study has also been started on a progesterone agent which is completely different from conventional sex hormone agents. Anti-estrogen agent is widely accepted for post-operative adjuvant endocrine therapy of breast cancer taking over as the conventional post-operative adjuvant chemotherapy, and also as a partner of chemo-endocrine therapy.

Topics: Androstanols; Breast Neoplasms; Castration; Clinical Trials as Topic; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Double-Blind Method; Female; Fluoxymesterone; Humans; Lymphatic Metastasis; Mastectomy; Menopause; Middle Aged; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Testosterone

A new antiestrogenic steroid, 2alpha, 3alpha-epithio-5alpha-androstand-17beta-yl 1-methoxy-cyclopentyl ether, mepitiostane, given orally 10 mg b.i.d. to 50 patients with advanced breast cancer, produced objective regression of the tumor in 17 cases (34%). Objective regression of the metastases was seen in 20 of the 48 control patients given fluoxymesterone, 10 mg b.i.d. orally (47.7%). These figures do not differ significantly. The study was a prospective, randomized, double-blind trial employing the protocol of the Cooperative Breast Cancer Group. There was a significantly lower incidence of hepatotoxicity in the patients given mepitiostane.

Topics: Administration, Oral; Age Factors; Androstanes; Androstanols; Breast Neoplasms; Clinical Trials as Topic; Double-Blind Method; Estrogen Antagonists; Female; Fluoxymesterone; Humans; Liver; Menopause; Middle Aged; Neoplasm Metastasis; Remission, Spontaneous; Sulfides

Although numerous reports have been published on the incidence of second cancers after adjuvant therapy for early breast cancer, there have been few studies on the effect of the development of second cancer on overall survival (OS) of the patients. 1857 female patients younger than 80 years of age with operable breast cancer with UICC Stages I, II, and III who entered 3 trials of adjuvant therapy were studied for the detection of recurrence and second cancer. The median follow-up period for surviving patients was 12 years (range, 5-25 years). 384 of recurrence and 119 of second cancers occurred. 465 deaths were recorded, the causes of which were designated to be due to recurrence of breast cancer in 326 patients, second cancers in 57, and due to other causes in 82. Many background factors that were significantly related to recurrence did not influence the incidence of and death by second cancers after mastectomy: age and menopausal status alone were related. The difference in the Kaplan-Meier curves between the event (recurrence and second cancers)-free and relapse-free survivals indicates the incidence of second cancers is a significant event in post-operation course of early breast cancer patients (P=0.0001). The survival curve of patients who were free from recurrence- and second cancer-death is shown to be significantly lower than that of those free from breast cancer-specific death (P=0.0355), suggesting that death by second cancers is significantly influential to the overall survival. According to the Cox regression model using a recurrence or second cancers as time-dependent variables, the diagnosis of a recurrence or second cancer is shown to be highly significant to OS of the patients (hazard ratio: 49.3, and 6.3, respectively). Second cancers are shown to be not statistically significantly influential to the breast cancer specific survival (P=0.0637), nor a recurrence to second cancer specific survival (P=0.2285). In spite of heterogeneous distribution of sites of second primary cancers and their different natural histories, the incidence of second cancer has a significant effect on the postoperative survival of early breast cancer patients. In the survival analysis of early breast cancer patients, we have to estimate the contribution of second cancers to properly evaluate the effect of treatment.

Topics: Adult; Androstanols; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyclophosphamide; Female; Follow-Up Studies; Humans; Incidence; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Ovariectomy; Prognosis; Survival Analysis; Tamoxifen

Two cases of primary advanced breast cancer and 4 cases of recurrent breast cancer were treated with cyclophosphamide, Adriamycin and FT-207 combined with hormone therapy. Adriamycin (20 mg) was injected twice a week, and an intravenous drip infusion of cyclophosphamide 150 mg), and FT-207 (400 mg) was administered daily for 3 weeks. Oophorectomy was performed in 4 cases and combination administration of tamoxifen and calcitonin was continued. CR was achieved in one of the primary cases, PR was obtained in 4 cases but one patient with pulmonary metastasis died without showing any clinical response. All cases with bone metastasis responded well. Leucopenia, alopecia, nausea and masculinization were easily controlled. No cardiac toxicity was observed.

Topics: Adult; Aged; Androstanols; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Calcitonin; Cyclophosphamide; Doxorubicin; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Recurrence, Local; Tamoxifen

The steroidal antiestrogen, mepitiostane (Thioderone, 2 alpha, 3 alpha-epitio-5 alpha-androstane-17 beta-yl 1-methoxycyclopentyl ether) was administered orally to 182 patients with operable breast cancer as an adjuvant therapy after mastectomy intermittently for 3 years. The mean duration of follow-up was 32 months (6 approximately 42 months). The treatment failure ratio and the time distribution of failure among those given mepitiostane were compared with those of 96 patients treated with mitomycin C. There was a recurrence of malignancy in 11.5% (21/182) of patients treated with mepitiostane and in 15.6% (15/96) of patients given mitomycin C. The recurrence rates of the postmenopausal patients treated with mepitiostane and those treated with motomycin C were 3.8% (3/80) and 17.6% (18/102), respectively. In contrast, the malignancy relapsed in 24.0% (14/39) and in 2.4% (1/42) of the premenopausal patients given mepitiostane and those given mitomycin C, respectively. Estrogen and progestrone receptors (ER, PgR) were assayed in some of the primary breast cancers. Although there was no difference in recurrence rate between the ER-positive and -negative cases, the recurrence rate of the patients with ER(+)PgR(+) tumors treated with mepitiostane was shown to be lower than those with ER(+)PgR(-) or ER(-)PgR(-) tumors. The antiestrogen mepitiostane may thus be useful in postmenopausal patients, in whom the adjuvant chemotherapy was less effective in preventing the recurrence of malignancy.

Topics: Androstanols; Breast Neoplasms; Female; Humans; Mastectomy; Menopause; Mitomycins; Postoperative Period

For more precise prediction of response to endocrine therapy in patients with advanced breast cancer, we investigated the correlation between the presence of combination of estrogen (ER), progesterone (PgR) receptors, or combination of ER, PgR and androgen receptor (AR) and response to therapy. The patients with ER+, PgR+ tumors survived longer than those with ER+, PgR-, or ER-, PgR- tumors. A better response rate with longer survival time was obtained in patients with tumors that had three positive receptors or PgR+ and/or AR+ in addition to ER+ than in those with tumors of other combinations. According to the sequential assays of ER in tumors in several stages of breast cancer, it is likely that the positive rate of ER becomes lessened by the progression of cancer and by treatments. We stressed the significance of steroid hormone receptor assay in the mastectomy specimens for the prediction of response of therapy in case of the future recurrence of malignancy.

Topics: Adrenalectomy; Androstanols; Antineoplastic Agents; Breast Neoplasms; Castration; Female; Humans; Mastectomy; Prognosis; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Receptors, Steroid; Tamoxifen

A new, orally active antiestrogenic steroid, mepitiostane (20 mg/day), was given to 45 patients with advanced breast cancer. The regression rate was 31.1%, or 14 of 45 patients, and a duration of regression of greater than 6 months was obtained in seven patients. Virilizing effects such as hoarseness, hirsutism, and acne were observed relatively often, but there was no evidence of abnormality in the liver function tests or in the serum calcium level.

Topics: Androstanes; Androstanols; Breast Neoplasms; Estrogen Antagonists; Female; Humans; Sulfides

Topics: Androstanes; Androstanols; Breast Neoplasms; Estrogen Antagonists; Female; Humans; Menstruation Disturbances; Receptors, Estrogen; Sulfides