Weiss L, Mayhew E
Cancer Drug Deliv. 1985 Winter;2(1):19-33. doi: 10.1089/cdd.1985.2.19.
Previously reported analyses of autopsy data gathered from patients dying from the sequelae of adenocarcinomas of the upper rectum revealed a step-wise sequence in the development of distant metastases. First, dissemination via the portal vein led to secondary hepatic metastases. Cancer cells from these liver metastases (not the primary cancer) disseminated via the inferior vena cava to generate tertiary pulmonary metastases. Cancer cells from the lung metastases (not the primary or secondary cancers) then disseminated via the arterial route to give rise to metastases in other organs. We propose a protocol for the treatment of patients with upper rectal carcinomas, based on the expectation that, at different times after diagnosis, some patients will have no distant metastases, metastases in the liver only, or in the liver and lungs only. The protocol for therapy is based on currently available liposome technology, by means of which high doses of drugs can be targeted to the liver and lungs containing the metastases, yet distinct from the metastases. It is argued that selective local delivery of this type would increase the dose of cytotoxic agent delivered, thereby increasing the chances of overcoming the relative drug-resistance of the metastatic cancer cells and, at the same time, reduce the risk of nonspecific toxicity. Liver and lung-selective liposomes could, when necessary, be delivered at the same time, in the same systemic venous infusion.
先前对因上段直肠癌后遗症死亡患者的尸检数据进行的分析显示，远处转移的发展存在一个逐步的过程。首先，通过门静脉扩散导致继发性肝转移。这些肝转移灶（而非原发性癌症）的癌细胞通过下腔静脉扩散，形成三级肺转移。然后，肺转移灶（而非原发性或继发性癌症）的癌细胞通过动脉途径扩散，在其他器官形成转移。我们基于这样的预期提出了一种上段直肠癌患者的治疗方案，即在诊断后的不同时间，一些患者将没有远处转移，仅肝脏有转移，或仅肝脏和肺有转移。该治疗方案基于目前可用的脂质体技术，通过该技术可以将高剂量药物靶向到含有转移灶的肝脏和肺部，但与转移灶不同。有人认为，这种类型的选择性局部给药会增加细胞毒性药物的给药剂量，从而增加克服转移性癌细胞相对耐药性的机会，同时降低非特异性毒性的风险。必要时，肝脏和肺选择性脂质体可以在同一全身静脉输注中同时给药。
