In an accompanying editorial on the E1684 ECOG trial
In an accompanying editorial on the E1684 ECOG trial, Balch and Buzaid questioned the role of adjuvant IFN- alpha in a high risk for recurrence patient whose tumor is greater than 4.0 mm thick and lymph node examination is clinically negative. Although excluded from the ECOG eligibility criteria for the E1684 trial, these patients have a greater than 60% chance of harboring microscopic nodal metastases and therefore may benefit from adjuvant high-dose interferon therapy. Knowing the pathologic status of the regional nodes in patients with thick melanomas provides important prognostic information. Patients with thick melanomas who have negative nodes have a significantly better prognosis than those with positive nodes (58% to 71% versus 32% to 42%). The available data from the ECOG E1684 trial were derived from patients whose lymph node pathology was known. The benefit of this therapy was seen for patients who entered the trial with lymph node involvement by comparison with the small subgroup of patients with thick, lymph node negative tumors. These authors therefore recommended that patients with melanomas greater than 4.0 mm have a nodal staging procedure, preferably intraoperative lymphatic mapping and sentinel lymph node biopsy, since this is the least morbid approach. Extrapolation of the results of E1684 may be considered for patients with local recurrences, satellite lesions, or in-transit metastases. Important questions that remain to be answered are whether the high-dose intravenous induction is necessary (or may in fact be sufficient to obtain the benefit of the E1684 treatment) and whether more prolonged interferon administration would enhance the benefit. In addition, the question remains whether early IFN- alpha therapy (after microscopic nodal metastases are removed) is better than late adjuvant therapy (after grossly positive nodal disease is resected with a therapeutic node dissection).
Human growth hormone information
Only a small subset of patients who receive high-dose IFN- alpha2b therapy actually derived benefit from it. Serum markers of tumors may provide a key to the more selective application of adjuvant therapy. Tyrosinase (a key enzyme in melanin biosynthesis whose gene is actively expressed only in melanocytes, melanoma cells, and Schwann cells) may serve as a marker of early dissemination of disease to allow more selective use of adjuvant therapy in the future. Because melanocytes and melanoma cells do not usually circulate in the blood, the detection of tyrosinase mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in blood is considered a potential indication of the presence of circulating melanoma cells. Patients who have a positive RT-PCR before starting therapy that subsequently becomes negative may be those who benefit from the therapy. Human Growth Hormone
The North Central Cancer Treatment Group (NCCTG 83-7052) evaluated the adjuvant role of IFN- alpha2a given at 20 MU/IM three times weekly for 3 months, versus observation in patients with 1.69-mm Breslow depth T3+ or T4, and N1 patients (subsets of AJCC stages IIA or IIB and III). An analysis of 260 evaluable patients who entered this trial demonstrates no significant prolongation of survival, or of relapse-free interval overall. Subset evaluation of patients in stage II as opposed to those in stage III participating in this trial reveals a potential impact in the latter, by Cox analysis.