Jones R B, Myers C E, Guarino A M, Dedrick R L, Hubbard S M, DeVita V T
Cancer Chemother Pharmacol. 1978;1(3):161-6. doi: 10.1007/BF00253116.
The currently accepted therapies for ovarian cancer have produced only limited numbers of extended complete remissions in advanced-stage disease. Studies of high-volume intraperitoneal chemotherapy have been initiated to define the toxicology, pharmacokinetics, and the therapeutic effectiveness of this treatment modality. This technique has been virtually ignored until recently, because little success has been achieved with it except in one study (Rutledge, 1966), in which large intraperitoneal fluid volumes were used. The general lack of success probably reflects inadequate attention to physiologic and pharmacologic principles of drug distribution and absorption in a space as large as the peritoneal cavity. Biomedical engineers, pharmacologists, and clinicians at the NCI have cooperated in the development of a rational chemotherapy for ovarian cancer. Following mathematical pharmacokinetic modeling and toxicologic studies in rat, a Phase I clinical trial of intraperitoneal methotrexate administered in large volumes of dialysis fluid was initiated. Results in three patients confirm the practicality of this approach, and further investigation is warranted.
目前公认的卵巢癌治疗方法在晚期疾病中仅产生了有限数量的长期完全缓解。已经开展了大容量腹腔内化疗的研究，以确定这种治疗方式的毒理学、药代动力学和治疗效果。直到最近，这项技术实际上一直被忽视，因为除了一项研究（拉特利奇，1966年）外，几乎没有取得成功，该研究使用了大量腹腔内液体。普遍缺乏成功可能反映出对药物在像腹腔这样大的空间中分布和吸收的生理和药理原理关注不足。美国国立癌症研究所的生物医学工程师、药理学家和临床医生合作开发了一种合理的卵巢癌化疗方法。在大鼠进行数学药代动力学建模和毒理学研究之后，启动了一项用大量透析液腹腔内注射甲氨蝶呤的I期临床试验。三名患者的结果证实了这种方法的实用性，值得进一步研究。
