Megestrol acetate and aminoglutethimide/hydrocortisone in sequence or in combination as second-line endocrine therapy of estrogen receptor-positive metastatic breast cancer: a Southwest Oncology Group phase III trial.

PURPOSE: A phase III randomized trial was performed to determine whether combination hormonal therapy with aminoglutethimide (AG) and hydrocortisone (HC) plus megestrol acetate (MA) improved response rates, response duration, or increased survival over the sequential use of each hormone in women with estrogen receptor-positive metastatic breast cancer (MBC) who had maintained stable disease for at least 6 months or responded to tamoxifen. PATIENTS AND METHODS: Two hundred eighty-eight postmenopausal women with progressive estrogen receptor-positive MBC were randomly selected to receive MA 40 mg four times daily (arm I), AG 250 mg four times daily with HC 40 mg daily in divided doses (arm II), versus the combination of MA plus AG given at the same dosages (arm III). Patients on arms I and II who progressed after an adequate trial were crossed over to the other treatment arm. RESULTS: Two hundred thirty-five eligible patients were evaluated for response, time to treatment failure, and survival. Response was only reported for patients with measurable disease and was not statistically different among the three arms. There were two partial responses (PRs) on MA (6%), four complete responses (CRs) and six PRs on AG (24%), and eight PRs and three CRs on MA plus AG (23%) in 32, 42, and 48 measurable patients, respectively. Median times to treatment failure were also similar at 5, 4, and 7 months. Survival was also not statistically different among the three arms at 26, 27, and 26 months for arms I, II, and III, respectively. Toxicity was greater in the two AG arms with respect to fatigue, nausea and vomiting, and rash. CONCLUSION: With the exception of toxicity, there is no response, time to treatment failure, or survival benefit for any one group when comparing MA, AG, or the combination at their stated doses in women with estrogen receptor-positive MBC who had previously responded to or stabilized with tamoxifen.

Phase II study of sequential methotrexate and 5-FU plus mitomycin and leucovorin in patients with disseminated large bowel cancer: a Northern California Oncology Group study.

Sequential methotrexate (MTX) and 5-FU plus leucovorin and mitomycin (MMC) was given to 52 patients with disseminated, measurable colorectal cancer. Complete and partial responses were seen in 19 of 49 (39%) evaluable patients. Nine additional patients achieved a minimal response. Median overall survival was 8.8 months, while that for patients objectively responding was 13.6 months. This study utilized a MTX exposure period of 12 hours prior to 5-FU. In comparison to other trials utilizing sequential MTX and 5-FU, the addition of MMC to the regimen may improve the response rate but increases the incidence of adverse effects, particularly myelosuppression and renal toxicity. This phase II trial suggests that sequential MTX and 5-FU plus leucovorin and MMC is an active combination therapy and warrants further comparative trial in patients with large bowel cancer.