Acute in vivo resistance in high-dose therapy.

摘要: In the design of sequential high-dose chemotherapy regimens, selection antitumor alkylating agents to be included in each intensification and interval between intensifications are critical therapy. The tumor cell survival assay growth delay using murine EMT-6 mammary carcinoma were used as a solid model which address these issues. Tumor-bearing mice treated with melphalan or cyclophosphamide followed 7 12 days later by melphalan, cyclophosphamide, thiotepa, carboplatin. After treatment both later, was resistant four drugs studied. thiotepa but not To extend treatments 14 21 days, after first transferred second hosts that either drug-treated drug treated. When melphalan-treated tumors high dose very 14-day less 21-day interval. This small effect evident bone marrow colony-forming unit, granulocyte-macrophage (CFU-GM), except pretreated melphalan. cyclophosphamide-treated resistance observed if host non-pretreated cyclophosphamide. same true CFU-GM. Tumor studies supported findings carboplatin resulted than additive delay, whereas prior additivity greater-than-additive delay. High-dose combination regimens required reduction drugs, decreased delays.