A Phase II Trial Of Isolated Hepatic Perfusion (IHP) With Melphalan For Subjects With Metastatic Unresectable Colorectal Cancers Of The Liver With Disease Refractory To First Line Systemic Chemotherapy

Date de début de l'étude : 1 juillet 2004

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed colorectal cancer * Metastatic disease limited to the parenchyma of the liver * Patients with limited sites of extrahepatic disease AND who have dominant life-limiting disease in the liver are considered eligible provided the extrahepatic sites can be treated with local ablative measures (e.g., resection or external beam radiotherapy) * No other evidence of unresectable extrahepatic disease by radiological studies * Unresectable hepatic disease defined by \> 3 sites of disease in the liver, bilobar disease, or tumor abutting major vascular or ductal structures making anatomic resection with liver function preservation impossible * Measurable disease * Refractory to prior first-line systemic chemotherapy * Disease progression during or after completion of treatment with an irinotecan- or oxaliplatin-containing regimen for established hepatic metastases * Treatment failure is defined as disease progression evidenced by tumor growth OR new lesions on imaging modalities OR increasing carcinoembryonic antigen (CEA) PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * Hematocrit \> 27.0% * Platelet count \> 100,000/mm\^3 * WBC \> 3,000/mm\^3 Hepatic * Bilirubin \< 2.0 mg/dL * PT ≤ 2 seconds of the upper limit of normal * ALT and AST elevations secondary to metastatic disease allowed * Chronic active hepatitis B or C allowed provided there is no evidence of cirrhosis on pathology, radiologic studies, or physical exam * No history of veno-occlusive disease * No biopsy proven cirrhosis * No evidence of significant portal hypertension manifested by ascites, esophageal varices on endoscopy, or radiologic studies showing significant collateral vessels around the organs drained by the portal venous system * No other liver condition that would preclude study therapy Renal * Creatinine ≤ 1.5 mg/dL OR * Creatinine clearance \> 60 mL/min Cardiovascular * LVEF ≥ 40% * No ischemic cardiac disease * No history of congestive heart failure Pulmonary * Chronic obstructive pulmonary disease or other chronic pulmonary disease allowed provided pulmonary function test ≥ 50% of predicted Other * Not pregnant or nursing * Negative pregnancy test * No active infection * Weight \> 30 kg PRIOR CONCURRENT THERAPY: Biologic therapy * More than 4 weeks since prior biologic therapy for the malignancy and recovered Chemotherapy * See Disease Characteristics * More than 4 weeks since prior chemotherapy for the malignancy and recovered Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * More than 4 weeks since prior radiotherapy for the malignancy and recovered Surgery * See Disease Characteristics Other * No concurrent immunosuppressive drugs * No concurrent chronic anticoagulation therapy