Fletcher W S, Pommier R F, Woltering E A, Mueller C R, Ash K O, Small K A
Department of Surgery, Oregon Health Sciences University, Portland 97201-3098.
Ann Surg Oncol. 1994 May;1(3):236-43. doi: 10.1007/BF02303529.
We analyzed prospectively collected data on 145 cis-platin hyperthermic isolation limb perfusion (HILPs) for melanoma and soft-tissue sarcoma to determine the pharmacokinetics and maximum tolerable dose of cis-platin. There were 70 melanoma and 75 sarcoma patients. Dosages ranged from 26 to 265 mg/m2. Perfusate and systemic cis-platin levels were measured in patients perfused at doses of 190-200 mg/m2. Tissue levels were measured in patients perfused at 123-209 mg/m2.
Cis-platin HILP was well tolerated up to doses of 250 mg/m2 for lower extremities. Higher doses produced toxicities of rhabdomyolysis, myoglobinuria, hyponatremia, and neuropathy. Systemic levels of cis-platin were equivalent to those of routine intravenous administration, while perfusate levels were 33 times higher. Tissue levels of cis-platin were five to six times higher than effective intravenous levels.
Six melanoma patients have developed local recurrences. All were perfused at doses < 120 mg/m2. However, regional nodal recurrences have occurred in six other patients perfused at doses < or = 200 mg/m2. Four sarcomas have recurred locally, but three of them were present at the time of perfusion.
We conclude that 250 mg/m2 is the maximum tolerable dose of cis-platin for lower-extremity HILPs. Neoadjuvant cis-platin HILP may improve local control rates for sarcomas. However, no tolerable dose of cis-platin provides control of nodal metastases from melanoma.
我们前瞻性分析了145例用于黑色素瘤和软组织肉瘤的顺铂热灌注隔离肢体灌注（HILP）的数据，以确定顺铂的药代动力学和最大耐受剂量。其中有70例黑色素瘤患者和75例肉瘤患者。剂量范围为26至265mg/m²。对接受190 - 200mg/m²剂量灌注的患者测量灌注液和顺铂的全身水平。对接受123 - 209mg/m²剂量灌注的患者测量组织水平。
下肢顺铂HILP在剂量高达250mg/m²时耐受性良好。更高剂量会产生横纹肌溶解、肌红蛋白尿、低钠血症和神经病变等毒性反应。顺铂的全身水平与常规静脉给药相当，而灌注液水平高33倍。顺铂的组织水平比有效静脉水平高五到六倍。
6例黑色素瘤患者出现局部复发。所有这些患者的灌注剂量均<120mg/m²。然而，另外6例灌注剂量≤200mg/m²的患者出现了区域淋巴结复发。4例肉瘤出现局部复发，但其中3例在灌注时就已存在。
我们得出结论，250mg/m²是下肢HILP顺铂的最大耐受剂量。新辅助顺铂HILP可能提高肉瘤的局部控制率。然而，没有可耐受剂量的顺铂能控制黑色素瘤的淋巴结转移。
