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 interleukin-2 (IL-2) based immunotherapies. MM with brain metastatis in particular, has 4-5 months life expectancy from metastasis to death. Drug efflux pumps such as P-glycoprotein (P-gp), or drug detoxifying mechanisms e.g. glutathion epsilon S-transferase-pi (GST) are some of the possible multidrug resistance (MDR) mechanisms in MM. Here we report the first P-gp+ MDR MM with brain metastasis in the literature, demonstrating a remarkable response to IL-2, interferon-alpha (IFN), 5-fluorouracil (5FU) regimen. A 41-year old man was admitted with multiple inoperable brain lesions. Biopsies from intracranial and dermal lesions revealed MM. Cisplatin, carmustine, dacarbazine, tamoxifen (CCDT) together with external cranial radiotherapy were administered, and partial response in lesions and symptoms was achieved. However, after the third course of CCDT treatment, he was admitted to the emergency ward with dramatically 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 18 months. Dermal lesions had not recurred since the beginning of immunotherapy. In contrast, another 34-year old man who developed brain metastases after CCDT for MM, was negative for P-gp and GST. Cranial radiotherapy was started and the above mentioned IL-2 based regimen was administered. However, no response was observed. These two cases together with previous studies demonstrating the susceptibility 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 good candidate for IL-2 based treatments.