REGIONAL CHEMOTHERAPY FOR CANCER - EXPERIENCES WITH 116 PERFUSIONS
REGIONAL CHEMOTHERAPY FOR CANCER - EXPERIENCES WITH 116 PERFUSIONS
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DOI：
10.1097/00000658-196004000-00024
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发表时间：
1960-01-01
影响因子：
9
通讯作者：
HEALEY, JE
中科院分区：
文献类型：
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作者：
STEHLIN, JS;CLARK, RL;HEALEY, JE
通过灌注技术实施的区域化疗提供了一种有趣的可能性，可以作为外科手术治疗选定的恶性肿瘤的辅助手段。Klopp和他的同事们显然在1950年首次描述了将化疗药物注射到身体特定部位的方法。3、14通过动脉内注射分次剂量，他们能够将氮芥末输送到特定区域，数量足以产生更明显的效果。肿瘤的变化比静脉给药后可能发生的变化更大。与此同时，他们提到了在治疗过程中使用心肺机来维持孤立的肿瘤肢体血液循环的可能性。同样在1950年，Bierman和他的同事观察到动脉内注射氮芥末比静脉注射更少的全身毒性。此外，他们还描述了将药物直接引入肿瘤区域的技术。6自从这些早期报告以来，国内外的研究人员已经在不同的位置对多种类型的癌症进行了动脉内注射各种化合物的实验。14-7，9-12在1958年，Creech等人进一步激发了人们对癌症区域化疗的兴趣，他们报告了通过体外循环灌流的结果。通过这一过程，在动脉血氧分压较高的情况下，大量药物可能被输送到孤立的四肢、器官或身体的某个区域。1957年12月，德克萨斯大学MD安德森医院首次在癌症患者的治疗和研究中使用灌注剂，到目前为止已经进行了116次(表1)。大多数被限制在四肢，少数被限制在骨盆，还有一些被限制在头部。超过一半的患者患有恶性黑色素瘤。使用的药物主要是烷化剂7R-二(2-氯乙基)-氨基-L-苯丙氨酸(苯丙氨酸芥末)和甲基-双(/3-氯乙基)胺盐酸盐(氮芥末)。关于这些试剂在水溶液或体液中的水解或分解，以及它们与特定成分(如核酸、蛋白质和酶)的反应能力，人们进行了广泛的研究。一般认为，它们干扰细胞核蛋白的代谢和组成，从而影响有丝分裂或细胞分裂的正常顺序。然而，是否所有烷基化试剂的作用方式都是相同的，还有待商榷。由于Luck 15，16观察到苯丙氨酸芥末在抑制或延缓小鼠黑色素瘤生长方面比其他药物更有效，我们的黑色素瘤患者605
REGIONAL chemotherapy administered by the perfusion technic offers interesting possibilities as an adjuvant to surgical treatment for selected malignant tumors. The administration of a chemotherapeutic agent to a specific part of the body apparently was first described in 1950, by Klopp and his associates.'3, 14 Byintra-arterial injections of fractionated doses, they were able to deliver nitrogen mustard to specific regions in amounts sufficient to produce more pronounced. changes in the tumor than were possible following intravenous administra-tion. At the same time, they mentionedthe possibility of employing the heart-lung machine to maintain the circulation in an isolated tumor-bearing extremity during the therapeutic procedure. Also in 1950, Bierman and his co-workers 5 observed that intra-arterial injections of nitrogen mustard vere followed byless systemic toxicity than were intravenous injections. In addition, they described technics wherebythe drug could be introduced directly into the area of the neoplasm. 6 Since these early reports, investigators both here and abroad have conducted experiments in intra-arterial injection of various compounds for many types of cancer in different locations. 14-7, 9-12 In 1958, interest in regional chemotherapy for cancer was further stimulated byCreech et al., 8 who reported their results with perfusion by means of an extracorporeal circuit. With this procedure, large amounts of a drug may be delivered to an isolated extremity, organ, or region of the body under high arterial oxygen tension. Use of perfusions in the treatment and study of patients with cancer was initiated in The University of Texas MD Anderson Hospital in December, 1957, and thus far 116 have been performed (Table 1). The majority have been confined to the extremities, a smaller number to the pelvis, and several to the head. More than half the patients have had malignant melanoma. The drugs chiefly employed have been the alkylating agents, 7r-di (2-chloroethyl)-amino-L-phenylalanine (phenylalanine mustard) and methyl-bis (/3-chloroethyl) amine hydrochloride (nitrogen mustard). These agents have been investigated extensively with respect to their hydrolysis or breakdown in aqueous solutions or body fluids, and also their reactivity with specific components, such as nucleic acids, proteins, and en-zymes. It is generally believed that they interfere with the metabolism and composi-tion of cellularnucleoprotein and thereby affect the normal sequence of mitosis or cellular division. Whether or not all alkylating agents act in the same general manner, however, is open to question. Since Luck 15, 16 observed that phenylalanine mustard was more effective in the inhibition or retarda-tion ofgrowth of mouse melanomas than other agents, our patients with melanoma 605