phase i-ii study of fluorouracil in combination with phenylbutyrate in advanced colorectal cancer

Conditions: Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Summary: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. interferon-gamma may interfere with the growth of tumor cells and slow the growth of the tumor. combining more than one drug with interferon-gamma may kill more tumor cells. this phase i/ii trial is studying the side effects and best dose of giving fluorouracil together with phenylbutyrate, indomethacin, and interferon-gamma and to see how well it works in treating patients with stage iv colorectal cancer

primary objectives: i. to determine in a phase i study the toxicity of flurouracil (fu) when given in escalating doses in combination with fixed doses of phenlylbutyrate (pb), indomethacin and recombinant human interferon-gamma (rhifng) to patients with advanced colorectal cancer. ii. to determine in a phase ii study the efficacy of fu in combination with pb, indomethacin and rhifng in patients with advanced colorectal cancer. outline: this is a dose-escalation study of fluorouracil (5-fu). phase i: patients receive 5-fu iv over 24 hours on day 1; phenylbutyrate iv over 120 hours and oral indomethacin daily on days 2-6; and interferon gamma subcutaneously on days 2, 4, and 6. courses repeat weekly in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of 5-fu until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity (dlt). phase ii :patients receive 5-fu, phenylbutyrate, indomethacin, and interferon gamma as in phase i at the mtd. patients are followed for survival. projected accrual: a maximum of 24 patients will be accrued for the phase i portion of this study and approximately 46 patients will be accrued for the phase ii portion of this study.

Eligibility criteria:
inclusion criteria: * stage iv colorectal adenocarcinoma, excluding brain metastases * histological confirmation of colorectal adenocarcinoma * previously untreated patients * previously treated patients * for the phase i trial, no limitations * for the phase ii trial, previous treated limited to adjuvant radiation and/or chemotherapy which is completed at least 12 months before documentation of metastatic disease; patients may not have received chemotherapy for metastatic disease * for the phase i trial, patients may have measurable disease or unmeasurable disease; for the phase ii trial, patients must have measurable disease in at least two dimensions on x-rays, ct scan or mri * expected survival of at least 16 weeks * performance status of \>= 70% (karnofsky) * wbc \>= 3000 ul * platelet count \>= 100,000/ul * bilirubin =\< 2 x uln * creatinine =\< 2 x uln * not pregnant and not lactating; women of child bearing age must have negative pregnancy test (beta-hcg) * no allergies to interferon-gamma or e.coli derived products * no serious medical intercurrent medical illnesses, including class iii or iv cardiovascular disease; patient may not be dependent on immunosuppressive drugs including corticosteroids, and may not receive these drugs for the entire duration of the study * no diarrhea, and with adequate oral intake * patients of child-bearing age and potential must agree to use adequate birth control other than oral contraceptives for the entire duration of the study * no previous or concurrent malignancy except inactive nonmelanoma skin cancer, in situ carcinoma of the cervix, grade 1 bladder cancer, or other cancers if the patient has been disease free for \>= 5 years * patients must be oriented and rational, and aware of the investigational nature of the study