Showing papers by "James N. Ingle published in 1988"

Randomized clinical trial of tamoxifen alone or combined with fluoxymesterone in postmenopausal women with metastatic breast cancer.

Abstract: A randomized clinical trial was performed to determine if combination hormonal therapy with tamoxifen (TAM) and fluoxymesterone (FLU) was more efficacious than TAM alone for the treatment of postmenopausal women with metastatic breast cancer. Patients failing TAM could subsequently receive FLU. The dose of both drugs was 10 mg orally twice daily. Objective responses were seen in 50 of 119 TAM patients (42%) and 63 of 119 TAM plus FLU patients (53%) (one-sided P = .05). Time to disease progression distributions were better for TAM plus FLU (median, 350 days v 199 days), but the log rank test only approached statistical significance (one-sided P = .07). Duration of response and survival distributions were similar between the two treatment arms. Toxicities, in terms of androgenic side effects, were greater on the TAM plus FLU regimen. Fifty-two patients are evaluable for response with FLU following TAM and 21 (40%) have achieved a response. We conclude that the advantages in terms of response rate and time to progression observed with TAM plus FLU probably represent a biological effect, but are not of sufficient magnitude to justify the routine clinical use of this combination given the lack of survival advantage and side effects encountered.

Microassay for nuclear binding of steroid receptors with use of intact cells from small samples of avian and human tissue.

Abstract: A micro version of a nuclear binding assay to assess the biological activity of receptors for steroid hormones was developed for application to small (needle) biopsies of human tumors for the purpose of predicting responses to steroid therapy. This easier assay requires 10-fold less tissue than the original nuclear binding assay described for progesterone receptors in the avian oviduct, endometrium, and endometrial carcinomas (Spelsberg TC, et al., Endocrinology 1987;121:631). We describe the application of this micro assay to normal avian oviduct and cancers of the human breast, and we demonstrate a tissue specificity and saturation of nuclear binding. The micro assay reliably measured as little as 0.5 mg equivalents of tissue per assay tube. Results for breast tumors determined to be estrogen-receptor-positive by the standard dextran-coated charcoal method were also determined with this nuclear binding assay. As described previously for progesterone receptors in endometrial carcinomas, some receptor-positive breast biopsies displayed negligible capacity for nuclear binding. Therefore, with the present assay we have identified nonfunctional receptors in these biopsies, which may be useful for accurate prediction of patients' responses to therapy with hormones.

Phase II evaluation of menogaril in women with metastatic breast cancer after failure of first-line chemotherapy.

Abstract: A total of 25 patients with metastatic breast cancer who had failed one prior chemotherapy regimen and had not received prior treatment with doxorubicin were treated with menogaril (200 mg/m2 i.v. over 1 h) every 4 weeks. Four patients (16%) achieved partial regressions lasting a median of 46 days. The median time to progression for all patients was 60 days and the median survival was 264 days. Seventeen patients subsequently received doxorubicin after removal from protocol and six (35%) achieved objective regression. We conclude that menogaril administered by the method that we employed has marginal activity in women with metastatic breast cancer after failure of prior chemotherapy. Failure to respond to menogaril does not preclude response to subsequent treatment with doxorubicin.

Progress report on a phase II trial of 5-fluorouracil plus citrovorum factor in women with metastatic breast cancer.

Abstract: 5-fluorouracil (FUra) has definite, albeit limited, antitumor activity against breast carcinoma (1). Inhibition of the enzyme, thymidylate synthetase (TS) by FdUMP, an active FUra metabolite, has been postulated as one biochemical mechanism for this antitumor activity (2). TS inhibition is markedly augmented by the presence of increased concentrations of the reduced folate, citrovorum factor (CF) (3). In 1985, preliminary information suggested that FUra plus CF resulted in more substantial activity against heavily pretreated metastatic breast cancer than would have been expected with FUra alone (4). This current study was designed 1) to study the antitumor activity and toxicity of FUra plus CF in metastatic breast cancer patients who had not been “heavily pretreated” with chemotherapy, 2) to examine the impact of this regimen on tumor TS activity, and 3) to correlate the degree of TS inhibition with clinical outcome. The protocol continues to accrue patients and this communication provides a progress report relating to antitumor activity and toxicity.