The effects of estrogen, progesterone, and tamoxifen alone and in combination with cytotoxic agents against human ovarian carcinoma in vitro

Article Abstract:

Ovarian cancer accounts for half of all deaths due to gynecologic cancer in the United States. Despite improvements in chemotherapy, advanced ovarian cancer remains largely refractory to conventional therapy. In order to evaluate possible chemotherapeutic regimens quickly, a tissue culture assay was developed in which growing colonies of human ovarian cancer cells, designated BG-1, could be tested for susceptibility to treatment. The tissue culture system was used to evaluate the effectiveness of hormonal treatments in combination with conventional cytotoxic chemotherapy. Estradiol, medroxyprogesterone acetate, or tamoxifen was added to cisplatin, doxorubicin, or cyclophosphamide. Observation of the growing colonies revealed that when given alone, tamoxifen inhibited cell growth, medroxyprogesterone increased cell growth, and estradiol increased cell growth marginally. When estradiol was given in combination with cytotoxic (cell-killing) agents, the mixture was no more effective than the cytotoxic agent alone. Marginal results were obtained with medroxyprogesterone in combination with the cytotoxic agents. However, tamoxifen produced additive improvement on the cytotoxic effects of cyclophosphamide. With either cisplatin or doxorubicin, the addition of tamoxifen was synergistic, i.e. better than merely additive. The results indicate that hormonal manipulation of cancer during chemotherapy may provide beneficial results. The prospect is especially appealing since substances like tamoxifen are essentially nontoxic, and improvements in chemotherapy might be achieved at little or no cost in worsened side effects. (Consumer Summary produced by Reliance Medical Information, Inc.)

Health aspects, Methods, Hormone therapy

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Responsiveness of patients with advanced ovarian carcinoma to tamoxifen: a Gynecologic Oncology Group study of second-line therapy in 105 patients

Article Abstract:

Epithelial ovarian cancer is treated with surgery and chemotherapy. If the disease recurs after this treatment, it is incurable. There is much reason to suspect that the development of this cancer is affected by hormones, including the fact that the incidence of this cancer rises dramatically as women approach menopause. For this reason, an attempt was made to use hormonal therapy in women with persistent or recurrent epithelial ovarian cancer. A total of 105 patients with advanced cancer were treated with tamoxifen, a drug which interferes with the response of cells to estrogen, a female hormone. A total of 19 patients responded to this treatment. In 10 cases, the response was complete. Unfortunately, the responses were not long-lasting; the average duration of the complete responses was 7.5 months and the longest duration of response was 17 months. Nine complete responders were evaluated for the presence of estrogen receptors on the surface of tumor cells; these receptors were found in eight of the nine cases, or 89 percent. Among the patients who had only stabilization of disease in response to treatment, or no response at all, only 59 percent were found to have estrogen receptors. This difference is not statistically significant, but is suggestive that estrogen receptors may be an important determinant of response to tamoxifen. Although the activity of tamoxifen against ovarian cancer is not great, the toxicity is minimal and the treatment should be considered for patients who are suffering progression of ovarian cancer despite previous treatment. (Consumer Summary produced by Reliance Medical Information, Inc.)

Estrogen, Estrogen antagonists

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