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