Phase III Randomized Study of Four Weeks High Dose IFN-2b in StageT3-T4 or N1 (Microscopic) Melanoma

Inclusion Criteria:

- Histologically confirmed primary melanoma of cutaneous origin

- Stage II (T3 N0 M0 1.5-4.0mm Breslow depth

- Clinically negative regional lymph node pathologic status unkown OR

- Histologically negative regional lymph nodes

- Stage III (T4 N0 M0)

- Greater than 4.0mm Breslow depth OR

- Stage III (T1-4 N1)

- One lymph node positive microscopically

- Patients must meet at least 1 of the following criteria

- T2b N0 primary melanoma 1.01-2.0mm with ulceration, node negative

- T3a-b N0 primary melanoma 2.01-4.0mm with and without ulceration, node
negative

- T4a-b N0 primary melanoma > 4.0mm with and without ulceration, node negative

- T1aN1a-2a (microscopic)-primary melanoma of any thickness with microscopically
positive lymph node (any number)

- Note EORTC patients who are node negative T2 or T3 are ineligible

- Patients with positive sentinel node should undergo complete lymphadenectomy of the
nodal basin prior to study

- Must complete all primary therapy (wide excision with or without lymphadenectomy) and
be randomized in the study within 84 days of wide excision

- No clinical, radiological/laboratory, or pathological evidence of incompletely
resected melanoma or any distant metastatic disease

- No clinically palpable lymphadenopathy

Age:

- 18 and over

Performance Status:

- ECOG 0-1

Life expectancy:

- Not specified Hematopoietic

- WBC at least 3,000/mm^3

- Platelet count at least 125,000/mm^3

- Hematocrit at least 30%

Hepatic:

- Bilirubin no greater than 2 times the upper limit of normal (ULN)

- AST, LDH, and Alkaline phosphate no greater than 2 times ULN

- If lactate dehydrogenase or alkaline phosphate is above normal, a contrast enhanced
CT scan or MRI of the liver is required to document the absence of tumor

Renal:

- BUN no greater than 33mg/dl OR

- Creatinine no greater than 1.8mg/dl

Cardiovascular:

- No history of active ischemic heart disease

- No cerebrovascular disease

- No congestive heart failure(New York Heart Association class III or IV heart disease)

Exclusion Criteria:

Biologic Therapy:

- No prior immunotherapy including tumor vaccines, interferon, interleukins,levamisole,
or other biologic response modifers for melanoma Chemotherapy

- No prior or concurrent chemotherapy Endocrine Therapy

- No concurrent systemic corticosteriods including oral steriods (i.e., prednisone,
dexamethasone), topical steroid creams or ointments, or any steriod-containing
inhalers.

Radiotherapy:

- No Prior or concurrent radiotherapy

Surgery:

- See Disease characteristics

Other:

- No other concurrent immunosuppressive medications

- No other history of invasive melanoma

- No autoimmune disorders or conditions of immunosuppression

- No other concurrent or prior malignancies within past 5 years

- Cancer in situ

- Lobular carcinoma in situ of breast

- Carcinoma in situ of the cervix

- Atypical melanocytic hyperplasia or Clark 1 melanoma in situ

- Basal or squamous cell skin cancer

- No evidence of organic brain syndrome or significant impairment of basal cognitive
function or any psychiatric disorder that would preclude study participation

- No other significant medical or surgical condition, or any medication or treatment
regimens, that would interfere with study participation.

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 6 months after study