A phase II trial of tamoxifen, premarin, methotrexate and 5-fluorouracil in metastatic breast cancer

Abstract

Complete remissions in patients with metastatic breast cancer using endocrine therapy or chemotherapy are infrequent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and the low complete remission rate may be related to this biochemical heterogeneity. Based on laboratory experiments using human breast cancer cells in tissue culture, a phase II protocol was designed using tamoxifen, premarin, methotrexate, and 5-fluorouracil. Thus far, twenty-nine (29) patients have been entered into this study and twenty-five (25) are currently evaluable for response. Overall response rate was 72%, and 14 of 25 (56%) attained a complete remission. Toxicity was minimal. Median nadir white blood cell count was 5,800 and median nadir platelet count was 252,000. In summary, this combination chemo-hormonal therapy regimen is effective with a more than 50% complete remission rate and minimal toxicity.

A comparison of cyclophosphamide, adriamycin, and 5-fluorouracil (CAF) and cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) in patients with advanced breast cancer

“…A multi-variate prognostic factor analysis has revealed that 75~ or greater of the prescribed dose of CAF over both a 6-week and a 24-week period of time is the factor most significantly associated with the achievement of a response and with the attainment of a long-term unmaintained response (10). Additional trials using alternating non-cross-resistant combinations and aggressive hormonal-cytotoxic approaches are underway (33,(35)(36)(37).…”

Efforts to combine endocrine and chemotherapy in the management of breast cancer: Do two and two equal three?

“…Basing his work on this trial and the experiments previously cited, Allegra and colleagues have conducted a highly similar trial in Kentucky (29). They used a treatment design consisting of ten days of tamoxifen followed by four days of premarin (estrogen) followed by high dose methotrexate, 5-fluorouracil, and leucovorin rescue.…”

Endocrine Treatment of Breast Cancer in Women

“…Clinical trials 1) Pilot studies. Several uncontrolled clinical trials have utilized estrogen priming in the treatment of locally advanced breast cancer as well as metastatic disease (291)(292)(293)(294)(295)(296). The salient features of these trials are summarized in Table 20.…”