A Multicenter Trial of Adjuvant Interferon Alfa-2b for Melanoma Patients With Early Lymph Node Metastasis Detected by Lymphatic Mapping and Sentinel Lymph Node Biopsy
- Compare the efficacy of regional lymphadenectomy with or without adjuvant high-dose
interferon alfa-2b on disease-free survival and overall survival of patients with
invasive cutaneous melanoma with early or submicroscopic sentinel lymph node metastasis
detected by histology or immunohistochemistry or by polymerase chain reaction (PCR).
- Compare the effect of lymphadenectomy vs observation on disease-free survival and
overall survival of patients with submicroscopic sentinel lymph node metastasis
detected only by PCR.
- Determine the recurrence rate and survival of patients with submicroscopic sentinel
lymph node metastasis detected only by PCR.
- Determine the positive and negative predictive value of reverse transcriptase PCR
analysis of sentinel lymph nodes and peripheral blood to identify patients at risk for
recurrence and death.
OUTLINE: This is a randomized, multicenter study. Patients in the randomized portions of
Protocols A and B are stratified according to tumor thickness (1-2 mm vs 3-4 mm vs greater
than 4 mm) and tumor ulceration (yes vs no).
All patients undergo wide local tumor excision with lymphatic mapping and sentinel node
biopsy. Patients with tumors with ambiguous drainage patterns undergo lymphoscintigraphy
prior to tumor excision. Patients with evidence of metastatic melanoma in the sentinel
node(s) by routine histology, serial sectioning, or immunohistochemistry and who have
undergone a prior regional lymph node dissection proceed to protocol A.
- Protocol A: Patients with metastasis in a single sentinel node with no evidence of
extracapsular extension and no metastatic disease in nonsentinel nodes are randomized
to 1 of 2 treatment arms.
- Arm I: Patients receive adjuvant high-dose interferon alfa-2b IV 5 days a week for
4 weeks, then subcutaneously 3 times a week for 48 weeks.
- Arm II: Patients undergo observation. Patients with metastases in more than one
sentinel node with evidence of extracapsular extension or metastasis in any
nonsentinel node receive adjuvant high-dose interferon alfa-2b as in arm I.
Patients with no evidence of sentinel node(s) metastases by routine histology, serial
sectioning, and immunohistochemistry and are negative by polymerase chain reaction (PCR)
analysis are observed.
- Protocol B: Patients with positive sentinel node(s) by PCR analysis are randomized to
one of three treatment arms.
- Arm I: Patients undergo observation.
- Arm II: Patients undergo lymph node dissection.
- Arm III: Patients undergo lymph node dissection followed by adjuvant high-dose
interferon alfa-2b IV 5 days a week for 4 weeks.
Patients are followed every 3 months for 2 years, every 4 months for 1 year, every 6 months
for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 5 years.
Allocation: Randomized, Primary Purpose: Treatment
Marshall M. Urist, MD
University of Alabama at Birmingham
United States: Federal Government
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|University of Alabama at Birmingham Comprehensive Cancer Center||Birmingham, Alabama 35294-3300|
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|
|James Graham Brown Cancer Center at University of Louisville||Louisville, Kentucky 40202|