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A Phase II Study of 5-Fluorouracil Administered as a One Hour Infusion in Combination With Calcium Leucovorin and Interferon Alpha-2A in Advanced Colorectal Cancer

Phase 2
Not Enrolling
Colorectal Neoplasms

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Trial Information

A Phase II Study of 5-Fluorouracil Administered as a One Hour Infusion in Combination With Calcium Leucovorin and Interferon Alpha-2A in Advanced Colorectal Cancer

This protocol will evaluate the activity of 5-Fluorouracil (FUra) given as a 1 hour infusion
in combination with leucovorin (LV) and interferon IFN alpha-2a in patients with advanced,
measurable colorectal cancer. IFN alpha-2a will be given at 5 million U/m(2) SC days 1-6;
LV, 200 mg/m(2), will be given as a short infusion over 30 minutes days 2-6, followed
immediately by a 1 hour IV infusion of FUra days 2-6. The starting dose of FUra will be 425
mg/m(2)/d(1). Cycles will be repeated at three week intervals provided that the granulocyte
count and platelet count have recovered to >e; 1200/microL and >e; 80,000/microL,
respectively, and all non-hematologic toxicity has resolved. The dose of FUra will be
adjusted according to individual tolerance. Preliminary experience with FUra given as a 1
hour infusion suggests that it is less toxic. The primary goal of this study is to
determine if this less toxic regimen retains clinical antitumor activity. FUra plasma
samples will be obtained the initial cycle at 50 and 55 minutes during the first 1 hour
infusion of FUra to permit documentation of achieved plasma levels and to permit correlation
between FUra pharmacokinetics and clinical toxicity and/or response. Pharmacokinetic
sampling will be repeated if the dose of FUra is increased or decreased in subsequent

Patients will be stratified according to whether or not they have received prior adjuvant
chemotherapy. A two-stage design will be employed for patients with no prior chemotherapy:
If less than or equal to 4 responses are seen among the initial 20 previously untreated
patients, accrual will cease. If greater than or equal to 5 responses are seen in the
initial 20 patients, however, accrual will be expanded to 40 patients.

Fourteen patients who have received prior adjuvant chemotherapy (completing it at least 6
months prior to study entry) or have received prior FUra only as a radiation sensitizer will
be entered. If no responses are seen, accrual to this cohort will cease. If greater than
or equal to 1 response is seen, accrual may be expanded to 24 patients.

Inclusion Criteria


Unresectable primary colorectal adenocarcinoma that is metastatic or recurrent.

Objectively measurable disease required.

No cerebral metastases.


Biologic Therapy:

No history of intolerance to interferon alfa (IFN-A).

At least 4 weeks since immunotherapy and recovered.

Chemotherapy: No prior chemotherapy for metastatic or recurrent disease. At least 6
months since adjuvant chemotherapy with fluorouracil (5-FU) in combination with
levamisole, leucovorin (CF), or IFN-A Interval waived for 5-FU (with or without CF) as a
radiosensitizer only . No dose-limiting toxicity with prior 5-FU.

Endocrine Therapy: Not specified

Radiotherapy: At least 2 weeks since palliative radiotherapy and recovered. Prior
definitive pelvic or whole or upper abdominal radiotherapy allowed in the absence of
current radiation enteritis.

Surgery: Prior surgery allowed with adequate healing/recovery

Patient Characteristics:

Age: 18 and over.

Performance status: ECOG 0 or 1.


AGC at least 2,000.

Platelets at least 100,000.

Hepatic: Bilirubin no greater than 2.0 mg/dL

Renal: Creatinine no greater than 2.0 mg/dL


No MI within the past year.

No active ischemic heart disease.

No NYHA class III/IV status.

No symptomatic arrhythmia.


No requirement for pharmacologic steroid doses for inflammatory or autoimmune disorders.
Physiologic replacement doses of steroids allowed.

No concurrent cimetidine or oxypurinol.

No HIV antibody.

No history of seizure disorder.

No active infection or other serious concurrent medical illness that would preclude

No second malignancy within 3 years except curatively treated: In situ carcinoma of
cervix, Basal cell carcinoma of the skin.

No pregnant or nursing women.

Effective contraception required of fertile patients.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

February 1995

Completion Date:

December 2000

Related Keywords:

  • Colorectal Neoplasms
  • Chemotherapy
  • Cytokine
  • Efficacy
  • Palliation
  • Solid Tumor
  • Neoplasms
  • Colorectal Neoplasms



National Cancer Institute (NCI) Bethesda, Maryland  20892