Selecting dose-intense drug combinations: metastatic breast cancer.
A mathematical model previously described is applied to the problem of selecting drug combinations for metastatic breast cancer. The model accounts for the differing single-agent activities of the drugs as well as their differing profiles of toxicity. With no bone marrow protection, combinations with cisplatin offer a small improvement in total equivalent dose over therapy with the more active single-agents. Restricting consideration to the four most commonly used agents, single-agent doxorubicin has the greatest equivalent dose. With protection for leukopenia or willingness to accept a higher incidence of severe leukopenia, a combination with large doses of cyclophosphamide, doxorubicin, and fluorouracil, and a small dose of cisplatin has greatest equivalent dose. The doublets cyclophosphamide/fluorouracil or fluorouracil/cisplatin at higher doses are almost as good. With protection for leukopenia and thrombocytopenia, a cyclophosphamide/thiotepa combination at very high doses maximizes total equivalent dose. This approach can be used to identify regimens worthy of prospective evaluation.
Biometric Research Branch, National Cancer Institute, Bethesda, MD 20892.
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D000470:Alkaloids / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009928:Organ Specificity; D017239:Paclitaxel
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel