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.

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal cancer
• Patients scheduled to receive mFOLFOX6 (in the adjuvant setting or for metastatic disease) as part of their chemotherapy regimen

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 6 months
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Serum creatinine ≤ 1.5 mg/dL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
• Fertile patients must use effective contraception
• Negative pregnancy test
• Not pregnant or nursing
• No serious concomitant systemic disorders, including active infection that, in the opinion of the investigator, would compromise the patient's safety or ability to complete the study
• No altered mental status precluding understanding of the informed consent process and/or completion of the necessary studies
• Must be able to follow protocol requirements and give informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Concurrent bevacizumab allowed
• No concurrent warfarin (Coumadin®)

• Concurrent enoxaparin (Lovenox®) allowed
• No concurrent theophylline or aminophylline
• No chocolate beginning 12 hours before day 1 of each course and through the end of that course's fluorouracil continuous IV