Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer

OBJECTIVES:

• Provide oxaliplatin in combination with fluorouracil and leucovorin calcium using the FOLFOX4 regimen for front-line treatment in patients with no prior chemotherapy for advanced colorectal cancer who are not eligible for entry into ongoing clinical trials of higher priority. (The regimen in this Treatment Referral Center protocol is one that was found to be superior in a recent national intergroup study.)
• Further determine the safety of this regimen in these patients.
• Further determine the anti-tumor activity of this regimen, defined as the rate of time-to-treatment failure, time to progression, and survival, in these patients.
• Capture data on subsequent salvage therapy administered to patients treated with this protocol.

OUTLINE: This is an open-label, multicenter study.

Patients receive oxaliplatin IV over 2 hours on day 1, leucovorin calcium IV over 2 hours on days 1 and 2, and fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Patients with clinical evidence of benefit from this treatment, defined as stable disease, partial response, or complete response as well as no increase in size of any measurable or evaluable lesion and no new sites of disease, may be eligible for additional courses.

Patients are followed until death.

PROJECTED ACCRUAL: A maximum of 300 patients per month will be accrued for this study.

DISEASE CHARACTERISTICS:

• Must not be eligible for Inter-group, Cooperative Group, or local clinical trials of higher priority
• Histologically or cytologically confirmed colorectal adenocarcinoma

• Locally advanced or metastatic
• Not curable by surgery or amenable to radiation therapy with curative intent
• Site of primary lesion must be or have been in the large bowel, as confirmed endoscopically, radiologically, or surgically
• No separate histological or cytological confirmation of metastatic disease is required for patients with a history of colorectal cancer treated by surgical resection who develop radiological or clinical evidence of metastatic cancer unless:

• More than 5 years has elapsed since prior primary surgery and the development of metastatic disease OR
• Primary cancer was a Duke's A or B1 lesion
• Measurable or evaluable disease
• No prior chemotherapy for advanced colorectal cancer

• Prior adjuvant therapy allowed for resected stage II, III, or IV disease with any regimen containing fluorouracil with or without irinotecan or with immunotherapy, provided recurrent disease has been documented

PATIENT CHARACTERISTICS:

Age:

• 15 and over

Performance status:

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy:

• Not specified

Hematopoietic:

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9 g/dL (transfusion allowed)

Hepatic:

• Bilirubin no greater than 1.5 mg/dL (regardless of liver involvement secondary to tumor)
• AST less than 5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 5 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No uncontrolled high blood pressure
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No myocardial infarction within the past 6 months
• No New York Heart Association class III-IV cardiac disease

Pulmonary:

• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• No pleural effusion or ascites that causes respiratory compromise (i.e., dyspnea grade 2 or greater)

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions to compounds of similar chemical or biologic composition to platinum agents or oxaliplatin as well as other study agents
• No neuropathy grade 2 or greater, regardless of causality
• No HIV-positive patients receiving combination anti-retroviral therapy
• No ongoing or active infection
• No uncontrolled concurrent illness
• No psychiatric or social situations that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No concurrent sargramostim

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy)

Surgery:

• See Disease Characteristics
• At least 4 weeks since prior major surgery (e.g., laparotomy)
• At least 2 weeks since prior minor surgery
• Insertion of a vascular access device is not considered major or minor surgery

Other:

• Recovered from effects of prior treatment
• No other concurrent investigational agents
• No oral cryotherapy on day 1 of each course