Liver Resection and Floxuridine Plus Fluorouracil and Leucovorin in Treating Patients With Liver Metastases From Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of surgery followed by floxuridine plus systemic fluorouracil and leucovorin in treating patients with liver metastases from colorectal cancer.

Detailed Description
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OBJECTIVES: Evaluate the efficacy of hepatic resection followed by portal vein infusion of floxuridine plus systemic fluorouracil/leucovorin calcium in patients with metastatic colorectal cancer. Study the toxic effects of adjuvant chemotherapy following hepatic resection. Evaluate mRNA expression of enzymes that may be important to the cytotoxicity of fluoropyrimidines in tumor cells, including thymidylate synthase, ribonucleotide reductase, and folylglutamyl synthetase, by polymerase chain reaction and immunohistochemistry. OUTLINE: Following resection of the liver and all extrahepatic colorectal cancer, patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks. If biopsy-proven metastatic disease develops, treatment may be stopped at the investigator's discretion. Continuation of regional therapy should be considered for extrahepatic failure. No concurrent radiotherapy is permitted. Patients are followed every 3 months for 3 years, then every 6 months for survival. PROJECTED ACCRUAL: It is expected that 50 patients will be entered over approximately 5 years.

Official Title
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Hepatic Resection Followed by Concurrent Adjuvant Portal Vein Infusion of Fluorodeoxyuridine and Systemic 5-Fluorouracil and Folinic Acid for Metastatic Colorectal Carcinoma

Conditions
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Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: floxuridine
* Drug: fluorouracil
* Drug: leucovorin calcium
* Procedure: adjuvant therapy
* Procedure: conventional surgery


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed colorectal carcinoma or radiologically confirmed colorectal carcinoma in a synchronous metastasis Intrahepatic metastases required No more than 15 metastases involving no more than 60% of functioning liver No extrahepatic disease unless: Resectable anastomotic or locally recurrent tumor Resectable mesenteric lymph node involvement in patients undergoing initial resection of primary colorectal carcinoma Disease extension from liver metastasis amenable to en bloc resection (e.g., diaphragm wall, kidney, abdominal wall) No biopsy-proven chronic active hepatitis PATIENT CHARACTERISTICS: Age: Physiologic 18 to 70 Performance status: Karnofsky 60%-100% Hematopoietic: AGC at least 1,500 Platelets at least 100,000 Hepatic: Bilirubin no greater than 2.0 mg/dL (unless reversibly obstructed by metastasis) Renal: Creatinine no greater than 2.0 mg/dL Other: No second malignancy within 5 years except adequately treated: Nonmelanomatous skin cancer In situ bladder cancer In situ cervical cancer No pregnant women PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior mitomycin or nitrosoureas allowed Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the liver At least 3 weeks since radiotherapy and recovered Prior pelvic radiotherapy allowed No planned concurrent radiotherapy Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin<br>Patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks | Drug: floxuridine<br>* Starting dose of 0.2 mg/kg/day for 14 consecutive days.<br>Drug: fluorouracil<br>* 300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.<br>Drug: leucovorin calcium<br>* 500 mg/m2/day by continuous intravenous infusion beginning 24 hours prior to the first dose of 5-FU and continuing until 12 hours following the last dose of 5-FU.<br>Procedure: adjuvant therapy<br>* Chemotherapy given after hepatic resection<br>Procedure: conventional surgery<br>* Hepatic resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 Year Disease-free Survival . | Estimated using the product-limit method of Kaplan and Meier. Disease free survival, defined as first documented evidence of treatment failure. Acceptable evidence includes: Anastomotic - positive cytology or biopsy; Abdominal, pelvic and retroperitoneal nodes - progressively enlarging node as evidenced by 2 CT scans separated by at least a 4 week interval, ureteral obstruction in the presence of a mass as documented on CT scan; Peritoneum - positive cytology or biopsy, progressively enlarged intraperitoneal solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Ascites - positive cytology or biopsy; Liver - positive cytology or biopsy; Pelvic mass - positive cytology or biopsy, progressively enlarging intrapelvic solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Abdominal wall - positive cytology or biopsy; Lung - positive cytology or biopsy or presence of multiple pulmonary nodules; Bone marrow - positive cytology, aspiration or biopsy. | 2 years after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, liver metastases