Liver Resection and Floxuridine Plus Fluorouracil and Leucovorin in Treating Patients With Liver Metastases From Colorectal Cancer
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.
|Colorectal Cancer Metastatic Cancer||Drug: floxuridine Drug: fluorouracil Drug: leucovorin calcium Procedure: adjuvant therapy Procedure: conventional surgery||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Hepatic Resection Followed by Concurrent Adjuvant Portal Vein Infusion of Fluorodeoxyuridine and Systemic 5-Fluorouracil and Folinic Acid for Metastatic Colorectal Carcinoma|
- 2 Year Disease-free Survival . [ Time Frame: 2 years after treatment ]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.
|Study Start Date:||September 1994|
|Study Completion Date:||May 2014|
|Primary Completion Date:||May 2014 (Final data collection date for primary outcome measure)|
Experimental: Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin
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
Starting dose of 0.2 mg/kg/day for 14 consecutive days.Drug: fluorouracil
300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.Drug: leucovorin calcium
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.Procedure: adjuvant therapy
Chemotherapy given after hepatic resectionProcedure: conventional surgery
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002842
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|Study Chair:||Lucille A. Leong, MD||City of Hope Comprehensive Cancer Center|