Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer
Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works in treating patients with advanced or metastatic colorectal cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients receive irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and cetuximab IV over 1-2 hours on day 1. Patients also receive fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity.
Pharmacokinetic and pharmacogenetic studies are also conducted.
DISEASE CHARACTERISTICS:
Histologically confirmed colorectal cancer
Scheduled to receive first- or second-line therapy for metastatic disease
No cerebral metastases or symptomatic or uncontrolled meningeal disease
PATIENT CHARACTERISTICS:
WHO performance status 0-2
ANC ≥ 2,000/mm^3
Platelet count ≥ 100,000/mm^3
Total bilirubin ≤ 2 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Alkaline phosphatase ≤ 5 times ULN
Not pregnant or nursing
Fertile patients must use effective contraception
No intestinal blockage
No complete dihydropyrimidine dehydrogenase deficiency
No chronic inflammatory disease of the colon
No other cancer except for nonmelanoma skin cancer or curatively treated carcinoma of the cervix or breast
No other severe condition, or condition that is likely to worsen, including any of the following:
No contraindication to atropine
PRIOR CONCURRENT THERAPY: