Bull J M
Cancer Res. 1984 Oct;44(10 Suppl):4853s-4856s.
Hyperthermia combined with chemotherapy is a complicated and poorly understood area, but one that portends great biological and clinical interest. The interrelationship of heat to vascular supply of tumor and normal organs that metabolize chemotherapy agents is complicated. The evocation of thermotolerance by chemical agents is a largely unexplored area. A class of chemotherapy agents that increase in cytotoxicity linearly with increasing temperature are the alkylating agents cisplatinum, mitomycin C, and mitoxantrone. A class of chemotherapy agents that increase in cytotoxicity only after a threshold temperature above 42 degrees are Adriamycin, bleomycin, and actinomycin D. Time sequencing of heat and Adriamycin affects cytotoxicity, implying a membrane effect of the heat and drug interaction. A new class of drugs thought not to be chemotherapy drugs because they are not cytotoxic at 37 degrees but are cytotoxic at greater than 41.5 degrees provides a new area of research. Chemotherapy agents that do not change in cytotoxicity with heat include the Vinca alkaloids, amsacrine, and 5-fluorouracil. In order to examine the complex interaction of heat and chemotherapy agents, whole animal models of tumor and normal tissue effects are extremely important.
热疗联合化疗是一个复杂且尚未被充分理解的领域，但它具有极大的生物学和临床研究价值。热与肿瘤及代谢化疗药物的正常器官血管供应之间的相互关系很复杂。化学药物诱发热耐受在很大程度上仍是未被探索的领域。一类细胞毒性随温度升高呈线性增加的化疗药物是烷化剂顺铂、丝裂霉素C和米托蒽醌。一类仅在温度高于42度的阈值后细胞毒性才增加的化疗药物是阿霉素、博来霉素和放线菌素D。热与阿霉素的时间顺序影响细胞毒性，这意味着热与药物相互作用存在膜效应。一类新的药物，因其在37度时无细胞毒性但在高于41.5度时有细胞毒性，所以被认为不是化疗药物，这提供了一个新的研究领域。细胞毒性不随热而改变的化疗药物包括长春花生物碱、安吖啶和5-氟尿嘧啶。为了研究热与化疗药物的复杂相互作用，肿瘤和正常组织效应的全动物模型极其重要。
