Hyperthermic isolated hepatic perfusion using melphalan for patients with ocular melanoma metastatic to liver.
OBJECTIVE
Liver metastases are the sole or life-limiting component of disease in the majority of patients with ocular melanoma who recur. Because median survival after diagnosis of liver metastases is short and no satisfactory treatment options exist, we have conducted clinical trials evaluating isolated hepatic perfusion (IHP) for patients afflicted with this condition.


METHODS
Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60-min hyperthermic IHP using 1.5 mg/kg of melphalan (mean total dose 105 mg). Via laparotomy, perfusion inflow was established with a cannula in the gastroduodenal artery and outflow via a cannula positioned in an isolated segment of the retrohepatic inferior vena cava. Portal and infra-renal inferior vena cava blood flow was shunted externally to the axillary vein using a veno-veno bypass circuit. Patients were assessed for toxicity, radiographic response, and survival.


RESULTS
There was no treatment related mortality and transient grade 3/4 hepatic toxicity was observed in 19 patients (65%). Mean length of operation and hospital stay was 8.3 h and 10 days, respectively. There were 3 (10%) complete responses (duration: 12, 14+, 15 months) and 15 partial responses (52%; mean duration: 10 months). The initial site of disease progression included liver in 17 of 25 patients (68%) who recurred. At a median follow-up of 30.7 months the median actuarial progression-free and overall survivals were 8 and 12.1 months, respectively.


CONCLUSIONS
IHP with melphalan alone results in significant regression of established liver metastases for patients with ocular melanoma. However, after IHP, disease progression is most commonly observed in the liver, and survival after disease progression is short. On the basis of a pattern of tumor progression predominantly in liver, continued clinical evaluation of hepatic directed therapy in this patient population is justified.
Alexander
H Richard
HR
Surgical Metabolism Section, Surgery Branch, Center for Cancer, National Cancer Institute,NIH, Bethesda, Maryland 20892-1502, USA. Richard_Alexander@nih.gov
Libutti
Steven K
SK
Pingpank
James F
JF
Steinberg
Seth M
SM
Bartlett
David L
DL
Helsabeck
Cynthia
C
Beresneva
Tatiana
T
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005134:Eye Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary*; D008279:Magnetic Resonance Imaging; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D010477:Perfusion; D013997:Time Factors; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan