toremifene and Ovarian-Neoplasms

The relation between the use of tamoxifen and gynecologic tumors has been documented. In this case, a 58-year-old postmenopausal woman had been treated with tamoxifen for 5 years followed by toremifene for 1.5 years due to the presence of stage II estrogen receptor-positive breast cancer. The patient was found to have a stage Ic granulosa cell tumor of the ovary despite undergoing annual gynecologic examinations. This report presents a case of granulosa cell tumor of the ovary after the long-term use of tamoxifen and toremifene.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Granulosa Cell Tumor; Humans; Middle Aged; Neoplasms, Second Primary; Ovarian Neoplasms; Tamoxifen; Toremifene

This study was performed to examine the effects of selective estrogen receptor modulators [tamoxifen (TAM) and toremifene (TOR)] and pure anti-estrogen, ICI-182780 (ICI, Faslodex) and soybean isoflavone, genistein (GE) on the expression of estrogen-stimulated c-fos/jun, ERalpha/beta and COX-1/2 in the uteri of ovarectomized mice. TAM, TOR, ICI and GE treatment significantly decreased the levels of estradiol (E2)-induced c-fos. ICI and GE treatment significantly decreased the levels of E2-induced c-jun and ERalpha expressions. High doses of TOR treatment significantly increased the E2-induced ERbeta expression. In contrast, ICI and GE treatment significantly decreased the levels of E,-induced COX-2 expression, thus suggesting that TOR and GE might prevent E2-related endometrial carcinogenesis.

Topics: Animals; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Genistein; Mice; Mice, Inbred ICR; Ovarian Neoplasms; Ovariectomy; Ovary; RNA, Messenger; Selective Estrogen Receptor Modulators; Tamoxifen; Toremifene

Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condition without a standard strategy of treatment.. We present the case of an ovarian luteinizing sclerosing thecoma in a 39-year-old woman. The patient underwent three laparotomic operations for subocclusive symptoms, revealing in both occasions the presence of sclerosing peritonitis, with large abdominal masses, including cysts containing clear fluid. Treatment with toremifene 20 mg/day and leuprolide resulted in a dramatic improvement of the performance status and complete remission of all the abdominal lesions. After 60 months follow-up, the patient is still disease-free.. Antiestrogens plus LHRH agonists might be a noninvasive, effective and well-tolerated therapy for sclerosing peritonitis in patient operated for luteinized thecomas.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leuprolide; Ovarian Neoplasms; Peritonitis; Sclerosis; Thecoma; Toremifene

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials as Topic; Drugs, Investigational; Estrogen Antagonists; Female; Humans; Lavandula; Male; Neoplasms; Oils, Volatile; Ovarian Neoplasms; Piperidines; Plant Oils; Plants, Medicinal; Prostatic Neoplasms; Raloxifene Hydrochloride; Retinoids; Tamoxifen; Toremifene

Antiestrogens (AEs) have been considered to elicit antitumor effects via estrogen receptor. However, recent reports have demonstrated that AEs had an antitumor effect even in cases without estrogen receptor, and that AEs caused various kinds of biological behavior such as a chemosensitizing effect. We therefore investigated the possibility of circumvention of cisplatin (CDDP) resistance due to the chemosensitizing effect of AEs by using 5 ovarian cancer cell lines. They were named KF, MH, KK, KFra and KFrb cell lines. KF and MH were derived from serous cystadenocarcinomas, and KK from a clear cell carcinoma. KFra and KFrb were CDDP-resistant cell lines developed from the KF cell line. MCF-7 cell line derived from breast cancer was used as a control. The study of a 50% inhibitory concentration (IC50) revealed that clomiphene (CLO) had the most potent antiproliferative effect among the AEs used, and was followed by tamoxifen (TAM) and toremifene (TOR) with a similar effect. On the whole, the degree of CDDP sensitivity was not correlated with the degree of AE sensitivity. KFra cell line which had the highest CDDP-resistance among the 5 ovarian cancer cell lines used was the most sensitive to AEs, especially to CLO. In the study on the combined administration of CDDP and AEs, 1 microM of CLO significantly reduced the IC50 of CDDP to KFrb, KK and MCF-7 cell lines. Similarly, 1 microM of TAM significantly reduced the IC50 of CDDP to KF, KFra and MCF-7 cell lines, and 1 microM of TOR significantly reduced it to KFra, KK and MCF-7 cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cisplatin; Clomiphene; Drug Resistance; Drug Synergism; Estrogen Antagonists; Female; Humans; Ovarian Neoplasms; Protein Kinase C; Tamoxifen; Toremifene; Tumor Cells, Cultured

The chemosensitizing effect of an antiestrogen, toremifene, was studied on 2 human ovarian cancer cell lines in vitro and on 3 fresh surgical ovarian tumor explants with the aid of the subrenal capsule assay (SRCA). Also, 11 patients with secondarily drug resistant, recurrent gynecologic cancer (8 ovarian and 3 uterine cancers) were treated with 240 mg toremifene daily for 1 week before each course of cytostatics. Toremifene potentiated the effect of doxorubicin on both cell lines. This was also the case on 1 cell line that was not completely resistant to doxorubicin. The SRCA showed a clear potentiating effect of toremifene only on the tumor overtly resistant to the combination of cisplatin, doxorubicin, and cyclophosphamide. Of the 11 patients treated with toremifene and cytostatics, the response of 8 patients was evaluable: 3 had partial response, 3 no change, and 2 progressive disease. Toremifene seems to have a chemopotentiating effect on gynecologic drug-resistant tumors.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Doxorubicin; Drug Resistance; Drug Synergism; Estrogen Antagonists; Female; Humans; Ovarian Neoplasms; Subrenal Capsule Assay; Tamoxifen; Toremifene; Tumor Cells, Cultured

The estrogen (ER) and progesterone (PgR) receptor levels in various gynecological tumors were measured. The same tumors were exposed in vitro to toremifene, MPA or their combination and the growth of the tumors was followed by measuring the adenosine triphosphate (ATP) within the cells by a simple bioluminescence assay. Altogether 34 clinical samples were studied. DMBA-induced mammary tumors bearing rats were treated in vivo with toremifene, MPA and their combination. About half of the ovarian cancers and 6 out of the 7 adenocarcinomas of uteri contained ER. The ovarian tumors were PgR rich in 25% and adenocarcinomas of uteri in 6 out of the 7 cases. When compared to control toremifene (concentration 1 mumol/l) was able to decrease the number of living cells to 50% or less in 9/34 samples, MPA (concentration 10 mumol/l) in 17/34 samples, and the combination in 25/34 samples. In five cases the antitumor effect of the combination was synergistic. In two cases signs of weak antagonism were seen. In vivo the antitumor effect of toremifene and MPA was clearly synergistic against DMBA-induced cancers. The effect was dose-dependent and at sufficiently high doses it was possible to eradicate the tumors and cure the animals.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Estrogen Antagonists; Female; Humans; Mammary Neoplasms, Experimental; Medroxyprogesterone; Medroxyprogesterone Acetate; Ovarian Neoplasms; Rats; Rats, Inbred Strains; Receptors, Estrogen; Receptors, Progesterone; Tamoxifen; Toremifene; Tumor Cells, Cultured

The antitumor effects of a new antiestrogen, Fc-1157a have been studied in vitro and in vivo. In vitro the effect of Fc-1157a was comparable to that of tamoxifen. The effect was dose-dependent, and at concentrations higher than 10(-6) mol/1 Fc-1157a induced real cell death of the MCF-7 cells. In DMBA-induced mammary cancer in rats Fc-1157a decreased the number of new tumors and inhibited the growth of existing tumors, these effects being statistically highly significant. The ratio of growing tumors to stable and regressing tumors was significantly decreased. Although these effects were slightly stronger with Fc-1157a than with tamoxifen, the difference between these two compounds was not statistically significant. Murine uterine sarcoma, an estrogen receptor-negative tumor, was resistant to tamoxifen, but was statistically significantly inhibited by high doses (100 and 200 mg/kg-1 day-1 for 5 days) of Fc-1157a. The antitumor effects of Fc-1157a are due mainly to the antiestrogenic activity. At high concentrations in vitro and at high doses in vivo Fc-1157a exerts antitumor effects some of which are different from those of tamoxifen and are directed even against estrogen receptor-negative tumors. The exact mechanism of the observed cytolytic effect at high doses is unknown.

Topics: Animals; Antineoplastic Agents; Cell Cycle; Cell Line; Estradiol; Estrogen Antagonists; Female; Humans; Mammary Neoplasms, Experimental; Mice; Mutagenicity Tests; Ovarian Neoplasms; Rats; Tamoxifen; Toremifene; Uterine Neoplasms