Relapse in the central nervous system in melanoma patients successfully treated with biomodulators

A number of partial or complete remissions have been induced within the past 3 years in patients with metastatic melanoma treated with biomodulators, such as low-dose cyclophosphamide (CY) and interleukin-2 (IL-2), or active specific immunotherapy. Six of the most successfully treated patients, with prolonged remissions in skin, lymph nodes, liver and/or lung, all had relapses in the brain. At the time of relapse in the CNS, remissions were continuing in the other viscera. A large single intracerebral metastasis was found in four of the six patients; the other two patients had three metastases each, one of which also had meningeal seeding. Resection was performed in the four patients with single lesions, without postoperative radiotherapy. Intrathecal IL-2 successfully controlled meningeal disease. To date, the median survival of the group exceeds 7 months, in contrast to the usual reported median of 1 to 4 months, reflecting the predominance of resectable single lesions. Immunological therapy failed to prevent or treat metastases to the CNS, but may have influenced the patients' reactivity to the disease, producing single rather than diffuse metastases. If melanoma is to be cured now by any systemic therapy, particularly biomodulation, new regional strategies must be devised to overcome the blood-brain barrier. By analogy with autoimmune disease of the CNS such as multiple sclerosis, in which excessive cell-mediated immunity is found, several possible immunological maneuvers are suggested.