A Phase II Trial of Isolated Hepatic Perfusion (IHP) and Systemic FOLFOX4 for Subjects With Metastatic Unresectable Colorectal Cancers of the Liver With ≥ 40% Hepatic Tumor Burden
A Phase II Trial of Isolated Hepatic Perfusion (IHP) and Systemic FOLFOX4 for Subjects With Metastatic Unresectable Colorectal Cancers of the Liver With ≥ 40% Hepatic Tumor Burden
RATIONALE: Drugs used in chemotherapy, such as melphalan, leucovorin, oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways may kill more tumor cells.
PURPOSE: This phase II trial is studying how well isolated hepatic perfusion with melphalan followed by combination chemotherapy works in treating patients with unresectable liver metastases from colorectal cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients undergo exploratory laparotomy. Patients with evidence of carcinomatosis not previously visualized on scans but found on surgical exploration are removed from the study. All other patients then undergo isolated hepatic perfusion (IHP). Once IHP is established, melphalan is administered intra-arterially over 3-5 minutes and then circulated throughout the liver for 1 hour. Approximately 6-12 weeks later, patients receive systemic chemotherapy comprising oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1-2. Courses with systemic chemotherapy repeat every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, after laparotomy, after completion of systemic chemotherapy, and then every 6 months thereafter.
After completion of study treatment, patients are followed every 3 months for 1 year, every 3-4 months for 2 years, and then every 6 months until disease progression.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study within 2-3 years.
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed colorectal cancer
Metastatic disease limited to the parenchyma of the liver
No evidence of unresectable extrahepatic disease by preoperative radiology
At least 40% hepatic replacement by tumor by axial CT scan or MRI
Unresectable liver metastases, defined by 1 of the following:
Measurable disease
Previously untreated disease
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Bilirubin < 2.0 mg/dL
PT < 2 seconds above upper limit of normal
Elevated transaminase levels allowed if due to liver metastases
No cirrhosis by biopsy
No significant portal hypertension as manifested by any of the following:
No chronic active hepatitis
No history of veno-occlusive disease
Renal
Cardiovascular
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other