Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver

H. Richard Alexander, Steven K. Libutti, James F. Pingpank, Seth M. Steinberg, David L. Bartlett, Cynthia Helsabeck, Tatiana Beresneva

Research output: Contribution to journalArticle

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Abstract

Purpose: 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. Experimental Design: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60min 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.

Original languageEnglish (US)
Pages (from-to)6343-6349
Number of pages7
JournalClinical Cancer Research
Volume9
Issue number17
StatePublished - Dec 15 2003
Externally publishedYes

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Melphalan
Melanoma
Perfusion
Liver
Neoplasm Metastasis
Disease Progression
Inferior Vena Cava
Survival
Length of Stay
Axillary Vein
Laparotomy
Disease-Free Survival
Research Design
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alexander, H. R., Libutti, S. K., Pingpank, J. F., Steinberg, S. M., Bartlett, D. L., Helsabeck, C., & Beresneva, T. (2003). Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver. Clinical Cancer Research, 9(17), 6343-6349.

Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver. / Alexander, H. Richard; Libutti, Steven K.; Pingpank, James F.; Steinberg, Seth M.; Bartlett, David L.; Helsabeck, Cynthia; Beresneva, Tatiana.

In: Clinical Cancer Research, Vol. 9, No. 17, 15.12.2003, p. 6343-6349.

Research output: Contribution to journalArticle

Alexander, HR, Libutti, SK, Pingpank, JF, Steinberg, SM, Bartlett, DL, Helsabeck, C & Beresneva, T 2003, 'Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver', Clinical Cancer Research, vol. 9, no. 17, pp. 6343-6349.
Alexander HR, Libutti SK, Pingpank JF, Steinberg SM, Bartlett DL, Helsabeck C et al. Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver. Clinical Cancer Research. 2003 Dec 15;9(17):6343-6349.
Alexander, H. Richard ; Libutti, Steven K. ; Pingpank, James F. ; Steinberg, Seth M. ; Bartlett, David L. ; Helsabeck, Cynthia ; Beresneva, Tatiana. / Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 17. pp. 6343-6349.
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abstract = "Purpose: 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. Experimental Design: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60min 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.",
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T1 - Hyperthermic Isolated Hepatic Perfusion Using Melphalan for Patients with Ocular Melanoma Metastatic to Liver

AU - Alexander, H. Richard

AU - Libutti, Steven K.

AU - Pingpank, James F.

AU - Steinberg, Seth M.

AU - Bartlett, David L.

AU - Helsabeck, Cynthia

AU - Beresneva, Tatiana

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N2 - Purpose: 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. Experimental Design: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60min 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.

AB - Purpose: 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. Experimental Design: Twenty-nine patients (male: 14, female: 15; mean age, 49 years) with unresectable liver metastases from ocular melanoma were treated with a 60min 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.

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