RATIONALE: Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, 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, may kill more tumor cells. Studying samples of blood in the laboratory from patients with cancer receiving fluorouracil in combination with oxaliplatin and leucovorin calcium may help doctors learn how fluorouracil works in the body and how patients will respond to treatment. PURPOSE: This phase I trial is studying biomarker-guided fluorouracil in treating patients with colorectal cancer receiving combination chemotherapy.
OBJECTIVES: Primary * To determine whether 4 courses of pharmacokinetic (PK)-guided 5-fluorouracil chemotherapy improves the ability to achieve a targeted area under the curve (20 to 25 mg\*hr/L) in patients with colorectal cancer receiving mFOLFOX6 chemotherapy as compared to historical non-PK-guided therapy in patients treated with a similar FOLFOX regimen. Secondary * To determine and compare the incidence of neutropenia and diarrhea in patients treated with these regimens. OUTLINE: This is a multicenter study. * Standard mFOLFOX6 (course 1): Patients receive fluorouracil IV bolus over 1-5 minutes followed by fluorouracil IV continuously over 46 hours, oxaliplatin IV over 2 hours, and leucovorin calcium IV over 2 hours on day 1. Patients undergo plasma sample collection periodically during study for pharmacokinetic (PK)-guided fluorouracil dose determination for courses 2-4. * PK-guided mFOLFOX6 (courses 2-4): Patients receive fluorouracil bolus, oxaliplatin, and leucovorin calcium as in course 1. Patients also receive fluorouracil\* IV continuously as determined by the PK-guided analysis. NOTE: \*The continuous infusion fluorouracil dose adjustment is calculated based on the results of PK plasma concentrations and the corresponding AUC from the preceding course.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
76
200-400 mg/m2 intravenously, 1 -5 minutes, once every 2 weeks 2400 mg/m2 intravenously over a period of 46 hours, once every 2 weeks
200-400 mg/m2, intravenously over a period of 2 hours, once every 2 weeks
85 mg/m2, intravenously for 2 hours, once every 2 weeks
Cancer Care of Western North Carolina
Asheville, North Carolina, United States
Moses Cone Regional Cancer Center at Wesley Long Community Hospital
Greensboro, North Carolina, United States
Leo W. Jenkins Cancer Center at ECU Medical School
Greenville, North Carolina, United States
Rex Cancer Center at Rex Hospital
Raleigh, North Carolina, United States
Marion L. Shepard Cancer Center
Washington, North Carolina, United States
Achievement of targeted AUC using pharmacokinetic (PK)-guided 5 fluorouracil as part of mFOLFOX6 therapy
Time frame: During first 4 cycles of drug therapy
Toxicity differences between PK-guided therapy versus non-PK-guided therapy
Time frame: 24 months
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