5-Fluorouracil Followed by Interferon-alfa-2b in Previously-treated Metastatic Gastrointestinal, Kidney, or Lung Cancer

Interferon with continuous infusion 5-Fluorouracil (5-FU) regimens have shown response rates
ranging from 0-43% in various cancers. Monthly bolus 5-FU + interferon-alfa-2b has not
undergone formal phase II testing. In a small pilot study, a 5 consecutive day schedule of
5-FU and interferon-alfa-2b resulted in the limiting toxicities of diarrhea and mucositis. A
more limited schedule was recommended. Therefore, it is reasonable to examine such a
schedule. In the current study, 5-FU will be followed by interferon-alfa-2b daily for 3 days
to attempt to benefit from both the biochemical and immunologic mechanisms described above.

Inclusion Criteria:

- Patients must have histologically-proven, metastatic gastrointestinal, kidney, or lung
cancer who have had disease progression on at least two prior systemic therapies.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 and
estimated survival of at least 3 months.

- Patients must be felt to have recovered from effects of prior therapy, such as past
expected white blood count nadir for chemotherapy (> 2 weeks for most agents, > 6
weeks for nitrosoureas or mitomycin-C)

- Patient consent must be obtained prior to entrance onto study.

- White blood count > 3500/mm3; platelet count of at least 100,000/mm3; hemoglobin > 9.0
gm/dl; bilirubin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT)
less than 3 times the upper limit of normal; serum creatinine < 1.8.

- Corticosteroids and immunosuppressive agents are not permitted during the course of
the study. Patients must have received no corticosteroids or immunosuppressive
medications at least 2 weeks prior to entrance on-study.

- Patients with elevated temperatures > 100.5 degrees F, must have sources of occult
infection excluded.

- Women of childbearing potential must have a negative pregnancy test and must take
adequate precautions to prevent pregnancy during treatment.

Exclusion Criteria:

- Evidence of significant cardiovascular disease including history of recent (< 6
months) myocardial infarction, uncompensated congestive heart failure, primary cardiac
arrhythmias (not due to electrolyte disorder or drug toxicity, for example) beyond
occasional PVC's, angina, or cerebrovascular accident.

- Prior history of psychiatric disorder that could be exacerbated by interferon therapy
or which could preclude completion of this therapy.

- Pregnancy or lactation.

- History of hypersensitivity to interferon alfa or fluoropyrimidines.

- History of severe debilitating pulmonary disease, such as chronic obstructive
pulmonary disease requiring continuous oxygen therapy.

- History of autoimmune disease requiring immunosuppression.

- Documented inflammatory joint or systemic inflammatory disease (such as Lupus) which
could be exacerbated by interferon therapy.