Cetuximab and Combination Chemotherapy in Treating Patients With Advanced or Metastatic Colorectal Cancer

OBJECTIVES:

Primary

• Improve hematologic and gastrointestinal tolerance to cetuximab and irinotecan hydrochloride, fluorouracil, and leucovorin calcium (FOLFIRI) in patients with advanced or metastatic colorectal cancer.

Secondary

• Increase the effectiveness of this regimen by intensifying the treatment.
• Specify the constitutional genetic and genomic tumor parameters that could interfere with and predict the toxicity and/or antitumor efficacy of this regimen.
• Assess the time to progression.

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

• Advanced or metastatic disease
• 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:

• Unstable heart disease
• Myocardial infarction within the past 6 months
• Active uncontrolled infection
• No contraindication to atropine

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior anticancer therapy
• More than 4 weeks since prior and no other concurrent investigational therapy
• Prior adjuvant chemotherapy allowed
• No prior fluorouracil or irinotecan hydrochloride
• No other concurrent anticancer therapy