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