OBJECTIVES:
Primary Objective:
* Compare the effect of high-dose interferon alfa-2b treatment on the relapse-free survival of patients with stage II or III resected malignant melanoma.
Secondary Objectives:
* Compare the effect of this treatment regimen on overall survival of these patients.
* Assess the toxicity of this treatment in these patients.
* Compare the effect of treatment on quality of life.
OUTLINE: This is a randomized study. Patients are stratified by pathologic lymph node status (known vs unknown),lymph node staging procedures(sentinel lymph node procedure vs. elective lymph node dissection vs. no lymphadenectomy), Breslow depth (\<= 1.0 mm vs. 1.01-2.0 mm vs. 2.01-4.0 mm vs \> 4.0 mm), ulceration of the primary lesion (yes vs. no vs. unknown), and disease stage (lymph node positive \[N1, N2a\] vs. lymph node negative \[N0\]). Patients are randomized into one of two treatment arms in a 1:1 ratio.
* Arm I (observation): Patients undergo observation for 4 weeks.
* Arm II (Interferon Alfa-2b): Patients receive high-dose interferon alfa-2b intravenously (IV) over 20 minutes daily for 5 consecutive days. Treatment repeats weekly for 4 weeks in the absence of unacceptable toxicity.
Quality of life is assessed before treatment, at day 22, every 3 months for 2 years, and then every 6 months for 3 years.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter until 15 years after randomization.
PROJECTED ACCRUAL: A total of 1,420 patients will be accrued for this study over 5 years.
Inclusion Criteria:
* Histologically confirmed primary melanoma of cutaneous origin
* Stage II (T3 N0 M0 1.5-4.0 mm Breslow depth)
* Clinically negative regional lymph node pathologic status unknown OR
* Histologically negative regional lymph nodes
* Stage III (T4 N0 M0)
* Greater than 4.0 mm 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 1.01-2.0 mm with ulceration, node negative
* T3a-b N0 - primary melanoma 2.01-4.0 mm with and without ulceration, node negative
* T4a-b N0 - primary melanoma \> 4.0 mm with or without ulceration, node negative
* T1a N1a-2a (microscopic) - primary melanoma of any thickness with microscopically positive lymph node (any number)
* Patients with a 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 this study within 84 days of wide excision
* Must have undergone an adequate wide excision of the primary lesion
* Age 18 and over (For ECOG patients only, patients must be \>=10 years)
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0-1
* Adequate hematopoietic, hepatic, and renal function based on the following tests:
* White blood cell (WBC) cout at least 3,000/mm\^3
* Platelet count at least 125,000/mm\^3
* Hematocrit at least 30%
* Bilirubin no greater than 2 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and alkaline phosphatase no greater than 2 times ULN
* If lactate dehydrogenase or alkaline phosphatase is above normal, a contrast-enhanced computed tomography (CT) scan or Magnetic resonance imaging (MRI) of the liver is required to document the absence of tumor
* Blood urea nitrogen (BUN) no greater than 33 mg/dL OR Creatinine no greater than 1.8 mg/dL
* No other concurrent or prior malignancies within the past 5 years except:
* Cancer in situ
* Lobular carcinoma in situ of the breast
* Carcinoma in situ of the cervix
* Atypical melanocytic hyperplasia or Clark 1 melanoma in situ
* Basal or squamous cell skin cancer
* Negative pregnancy test
* Fertile patients must use effective contraception during and for 6 months after study
Exclusion Criteria:
* Clinical, radiological/laboratory, or pathological evidence of incompletely resected melanoma or any distant metastatic disease
* Clinically palpable lymphadenopathy
* Evidence of organic brain syndrome or significant impairment of basal cognitive function or any psychiatric disorder that would preclude study participation
* Other significant medical or surgical condition, or any medication or treatment regimens, that would interfere with study participation
* Pregnant or nursing
* Other history of invasive melanoma
* Autoimmune disorders or conditions of immunosuppression
* History of active ischemic heart disease
* Cerebrovascular disease
* Congestive heart failure (New York Heart Association class III or IV heart disease)
* Prior or concurrent chemotherapy
* Prior immunotherapy including tumor vaccines, interferon, interleukins, levamisole, or other biologic response modifiers for melanoma
* Concurrent systemic corticosteroids including oral steroids (i.e., prednisone, dexamethasone), topical steroid creams or ointments, or any steroid-containing inhalers
* Prior or concurrent radiotherapy
* Other concurrent immunosuppressive medications
