Multidrug resistant malignant melanoma with intracranial metastasis responding to immunotherapy

Metastatic malignant? melanoma (MM) is well known for its poor response to chemotherapy, radiotherapy, and its remarkable susceptibility to interleuki n-2 (IL-2) based immunotherapies. MM with brain metastatis in particular, h as 4-5 months life expectancy from metastasis to death. Drug efflux pumps s uch as P-glycoprotein (P-gp), ol drug detoxifying mechanisms e.g. glutathio ne S-transferase-pi (GST) are some of the possible multidrug resistance (MD R) mechanisms in MM. Here we report the first P-gp(+) MDR MM with brain met astasis in the literature, demonstrating a remarkable response to IL-2 inte rferon-alpha (IFN), 5-fluorouracil (5FU) regimen. A 41-year old man was adm itted with multiple inoperable brain lesions. Biopsies from intracranial an d dermal lesions revealed MM. Cisplatin, carmustine, dacarbazine, tamoxifen (CCDT) together with external cranial radiotherapy were administer ed, and partial response in lesions and symptoms was achieved However; after the t hird course of CCDT treatment, he was admitted to the emergency ward with d ramatically increased intracranial lesions, and recurring dermal lesions. A biopsy from the recurred lesions revealed that MM cells were P-gp(+), but GST(-). Administration of a IL-2, IFN and 5FU regimen achieved a remarkable decline in the brain lesions with almost total disappearance of symptoms. He was well and capable of doing work for Is months. Dermal lesions had not required since the beginning of immunotherapy. In contrast, another 34-yea r old man who developed brain metastases after CCDT for MM, was negative fo r P-gp and GST. Cranial radiotherapy was started and the above mentioned IL -2 based regimen was administered ed However; Mo response was observed. The se two cases together with previous studies demonstrating the susceptibilit y of P-gp(+) MDR cancer cell lines to IL-2 activated killer (LAK) cells in this report suggest that P-gp(+) MDR MM is probably a goon candidate for IL -2 based treatments.