Rationale for mitomycin and irinotecan use in advanced breast cancer

For women who develop hormone-refractory metastatic breast cancer, or who have breast cancers that are not estrogen-dependent (hormone receptor-negative), treatment with chemotherapy is the best option. Mitomycin (Mutamycin) and irinotecan (CPT-11, Camptosar) have marginal activity in breast cancer. However, the sequential administration of mitomycin and irinotecan appears to have synergism in preclinical studies, as mitomycin upregulates the level of topoisomerase I, the target of irinotecan. A phase I clinical trial of pharmacologically based sequential administration of mitomycin on day 1 followed by irinotecan on days 2 and 8 was performed in previously treated solid tumor patients. In five heavily pretreated women with breast cancer, one patient had a complete response, one patient had a partial response, and one patient had stable disease. Upregulation of topoisomerase I gene expression in peripheral blood mononuclear cells was observed in two of the responding patients. A phase II trial of mitomycin followed by irinotecan in women with previously treated metastatic, inflammatory, or locally advanced breast cancer is currently ongoing.