PHARMACOKINETICS AND RESULTS OF DOSE-ESCALATION IN CISPLATIN HYPERTHERMIC ISOLATION LIMB PERFUSION

Background: We analyzed prospectively collected data on 145 cis-platin hyperthermic isolation limb perfusion (HILPs) for melanoma and soft-t issue sarcoma to determine the pharmacokinetics and maximum tolerable dose of cis-platin. There were 70 melanoma and 75 sarcoma patients. Do sages ranged from 26 to 265 mg/m2. Perfusate and systemic cis-platin l evels were measured in patients perfused at doses of 190-200 mg/m2. Ti ssue levels were measured in patients perfused at 123-209 mg/m2. Metho ds: Cis-platin HILP was well tolerated up to doses of 250 mg/m2 for lo wer extremities. Higher doses produced toxicities of rhabdomyolysis, m yoglobinuria, hyponatremia, and neuropathy. Systemic levels of cis-pla tin were equivalent to those of routine intravenous administration, wh ile perfusate levels were 33 times higher. Tissue levels of cis-platin were five to six times higher than effective intravenous levels. Resu lts: 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 less-than-or-equal-t o 200 mg/m2. Four sarcomas have recurred locally, but three of them we re present at the time of perfusion. Conclusions: 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 fo r sarcomas. However, no tolerable dose of cis-platin provides control of nodal metastases from melanoma.