Combination Chemotherapy in Treating Patients With Liver Metastases From Colorectal Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Metastatic Cancer; Colorectal Cancer

Treatments: Drug: fluorouracil; Drug: oxaliplatin; Drug: leucovorin calcium

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003834

NCCTG-974651

CDR0000066991 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients with liver metastases from colorectal cancer.

Full description

OBJECTIVES: I. Evaluate the efficacy of treatment with oxaliplatin, fluorouracil, and leucovorin calcium in terms of the resectability rate in patients with unresectable advanced colorectal carcinoma confined to the liver. II. Assess this regimen in terms of response rate, toxicity, and overall survival in these patients.

OUTLINE: Patients receive oxaliplatin IV over 2 hours on day 1, then leucovorin calcium IV over 2 hours with fluorouracil IV bolus, followed by fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 2 weeks. Patients with stable disease continue treatment in the absence of disease progression or unacceptable toxicity or until disease is resectable. Patients who achieve complete response (CR), partial response (PR) with unresectable disease, or PR but are not surgical candidates continue treatment in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a response are treated until best response or until disease is deemed resectable. Patients who achieve a CR or PR and are resected may receive 2 to 4 additional courses of therapy at the discretion of the investigator. Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

Enrollment: 44 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS: History of carcinoma of the colon or rectum in which the primary site has been completely resected Measurable or evaluable unresectable liver metastases with one or more of the following: Involvement of all 3 major hepatic veins, the portal vein bifurcation, or the retrohepatic vena cava Involvement of the main right or the main left portal vein and the main hepatic vein of the opposite lobe Disease requiring more than a right or left trisegmentectomy Six or more metastatic lesions distributed diffusely in both lobes of the liver

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin normal SGOT no greater than 3 times upper limit of normal (ULN) No chronic hepatic disease (e.g., chronic active hepatitis, cirrhosis) Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No history of myocardial infarction within the past 6 months No congestive heart failure Other: No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of any organ or other tumor associated with less than 10% probability of death from malignant disease within 5 years of diagnosis Adequate oral nutrition including estimated intake of at least 1,500 calories per day No severe anorexia or frequent nausea and/or vomiting Able to withstand a major operative procedure No neuropathy Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent immunotherapy Concurrent filgrastim or epoetin alfa allowed Chemotherapy: At least one year since prior adjuvant systemic fluorouracil with or without levamisole or leucovorin No prior systemic or hepatic artery infusion chemotherapy for metastatic disease No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the liver At least one year since radiotherapy to greater than 25% of bone marrow No concurrent radiotherapy Surgery: At least 21 days since abdominal exploration with or without intestinal resection Other: Oral cryotherapy allowed only on day 2 of each course

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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44 participants in 1 patient group

oxaliplatin + leucovorin + fluorouracil

Experimental group

Description:

Patients receive oxaliplatin IV over 2 hours on day 1, then leucovorin calcium IV over 2 hours with fluorouracil IV bolus, followed by fluorouracil IV over 22 hours on days 1 and 2. Courses repeat every 2 weeks. Patients with stable disease continue treatment in the absence of disease progression or unacceptable toxicity or until disease is resectable. Patients who achieve complete response (CR), partial response (PR) with unresectable disease, or PR but are not surgical candidates continue treatment in the absence of disease progression or unacceptable toxicity. Patients who demonstrate a response are treated until best response or until disease is deemed resectable. Patients who achieve a CR or PR and are resected may receive 2 to 4 additional courses of therapy at the discretion of the investigator. Patients are followed every 3 months for 1 year and then every 6 months for 2 years.

Treatment:

Drug: fluorouracil

Drug: leucovorin calcium

Drug: oxaliplatin