A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver

There are no satisfactory treatment options for patients with ocular melano ma metastatic to liver, and after liver metastases are identified, median s urvival is only between 2 and 7 months. Because liver metastases are the so le or life-limiting component of disease in the vast majority of patients w ho recur, we reasoned that complete vascular isolation and perfusion of the liver might result in clinically meaningful regression of disease. Between September 1994 and July 1999, 22 patients (13 women and 9 men; mean age, 4 9 years) with ocular melanoma metastatic to liver were treated with a 60-mi n hyperthermic isolated hepatic perfusion (IHP) using melphalan alone (1.5- 25 mg/kg, n = 11) or with tumor necrosis factor (TNF, 1.0 mg, n = II). Via a laparotomy, IHP inflow was via the hepatic artery alone (n = 17) or hepat ic artery and portal vein (n = 5) and outflow from an isolated segment of i nferior vena cava, Most patients had advanced tumor burden with a mean perc entage of hepatic replacement of 25% (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to >50), Complete vascular isolation wa s confirmed in all patients using a continuous intraoperative leak monitori ng technique with I-131 radiolabeled albumin. There was one treatment morta lity (5%), The overall response rate in 21 patients was 62% including 2 rad iographic complete responses (9.5%) and II partial responses (52%), The ove rall median duration of response was 9 months (range, 5-50) and was signifi cantly longer in those treated with TNF than without (14 versus 6 months, r espectively; P = 0.04), Overall median survival in 22 patients was 11 month s. These data indicate that a single 60-min IHP can result in significant r egression of advanced hepatic metastases from ocular melanoma, TNF appears to significantly prolong the duration of response.