Evaluation of selected compounds for estrus control in the bitch.

Steroidal and nonsteroidal compounds were evaluated for estrus inhibition in the bitch. Mibolerone, an anabolic steroid, was effective and appeared to be safe. The remaining compounds lacked efficacy or had extensive side effects, or both.

The use of antiestrogens tamoxifen and nafoxidine in the treatment of human breast cancer in correlation with estrogen receptor values. A phase II study.

Twenty-five patients with measurable metastatic breast cancer and assays for estrogen receptor (ER) were studied. Of the 16 ER positive patients on anti-estrogen therapy, one had complete disappearance of all tumor for seven months and seven patients had more than 50% reduction in their measurable tumor for an average duration of 8.8 months. Seven other ER positive patients had stabilization of their tumors for an average interval of 8.4 months. Only one of the 16 ER positive patients progressed promptly. Conversely there was only one partial response in the nine ER negative patients and only two ER negative patients had stabilization of disease. Six out of nine ER negative patients progressed promptly. Correlation existed between the duration of response and absolute estrogen receptor level of the tumor. There may be a positive correlation between the response to antiestrogen therapy and response to endocrine ablation but prospective studies must be done to further define the role of antiestrogens in this regard.

Antioestrogens in treatment of breast cancer: value of nafoxidine in 52 advanced cases.

The synthetic non-steroidal antioestrogen nafoxidine (U-11, 100A) was given by mouth to 52 women with locally advanced or metastatic breast cancer, in 85% of whom the disease had become resistant to, or relapsed after, previous endocrine treatment. The objective response rate (complete or partial regression of disease) among 48 cases treated for at least four weeks was 37%. Tumours in soft tissue seemed to respond better than skeletal metastases. The patients in all but one of the 52 cases were postmenopausal. Those who had had an objective response to previous hormone treatment had a greater chance of deriving benefit from nafoxidine than those who had been resistant to hormone treatment.Side effects of nafoxidine were dryness of skin, increased loss of scalp hair, and heightened sensitivity to sunlight. None were serious, and they could be lessened by protection from solar radiation or a decrease in dosage. No obvious depression of thyroid or adrenal function or obvious water retention or masculinization was seen. Cataract was a possible complication.This clinical trial was preceded by laboratory studies in which a transplantable oestrogen-dependent tumour in the Syrian hamster was notably inhibited by the administration of nafoxidine. This experimental model may prove useful in screening potentially useful antioestrogenic agents against breast cancer before a human trial.

Treatment of renal carcinoma: a phase III randomized trial of oral medroxyprogesterone (Provera), hydroxyurea, and nafoxidine.

Seventy patients with metastatic renal carcinoma were randomized to receive hydroxyurea, nafoxidine, or medroxyprogesterone (Provera) orally. Sixty patients were considered evaluable, with a response rate of 5% for medroxyprogesterone (one complete remission) and hydroxyurea (one partial remission) and a response rate of 16% for nafoxidine (two complete remissions and one partial remission). Differences in response rates and duration of survival were not statistically significant. The major toxicity observed with hydroxyurea was hematologic, and the major toxic effect of nafoxidine was an ichthyosis-like skin rash. Toxicity for medroxyprogesterone was minimal.

Comparative trial of nafoxidine and ethinyloestradiol in advanced breast cancer: an E.O.R.T.C. study.

A randomized clinical trial of nafoxidine, a non-steroidal oestrogen antagonist, and ethinyloestradiol in postmenopausal patients with advanced breast cancer produced objective remissions in 31% of 49 women receiving nafoxidine and in 14% of 49 receiving ethinyloestradiol. The differences in remission rates was almost significant (0.05 less than P less than 0.10). Life-threatening complications were more frequent with ethinyloestradiol than with nafoxidine but the latter produced specific toxic reactions on skin and hair that may limit its practical usefulness. Synthetic oestrogen antagonists may occupy a privileged place in the treatment of breast cancer, and other representatives of this new class of compounds should be accurately assessed in randomized clinical trials.

Tumour stimulation by anti-oestrogens.

Two women who developed tumour progression while taking anti-oestrogens are described and some of the possible mechanisms for this action are discussed.

Clinical trial of nafoxidine in advanced breast cancer.

Forty-nine postmenopausal patients with advanced breast cancer were treated with a nonsteroidal antiestrogen, Nafoxidine. The drug was generally well tolerated with dermatitis being the major toxic effect. A partial response in 12 of 40 patients, or 30%, was achieved with a median duration of response of greater than five months.

Nafoxidine--an antiestrogen for the treatment of breast cancer.

Nafoxidine is a nonsteroidal antiestrogen available as an investigational agent from the Investigational Drug Branch of the National Cancer Institute. It has been used effectively in the treatment of breast cancer patients. A cumulative response rate of 31% is reported for a total of 200 patients treated with this drug. Most patients have been treated with a dose of 60 mg three times a day. Side effects include dryness of skin, photosensitivity reactions and, less commonly, partial hair loss. There is a strong correlation of response to nafoxidine with the presence of estrogen receptor in the tumor and also with the response to previous hormonal treatment. Nafoxidine is a useful addition to the list of hormonal treatments in the therapy of breast cancer.

Therapeutic value of nafoxidine hydrochloride in the treatment of advanced carcinoma of the human breast.

Nafoxidine hydrochloride can provide additional palliation to patients who responded to previous endocrine ablation and had tumors containing an estrogen receptor. In the present study, 24 patients were evaluated for their response to nafoxidine therapy, 180 to 240 milligrams given orally per day. When tumor response was obtained, doses were reduced to 60 to 120 milligrams every other day or longer without loss of control. In the estrogen receptor positive group, eight of ten patients responded objectively to nafoxidine, while all seven estrogen receptor negative patients progressed with this therapy. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. Patients with lesions to other sites should receive cytoxic agents along with nafoxidine. Alternative therapy to nafoxidine should be considered for patients in whom the tumors contain negligible estrogen receptor.