Clinical complete long-term remission of a patient with metastatic malignant melanoma under therapy with indisulam (E7070).

摘要

The objective of this study is to report on long-term survival of a patient with metastatic melanoma treated with indisulam showing a distinct genetic pattern of repression of subsets of genes involved in mitochondrial energy metabolism. Gene expression profiling was performed with oligonucleotide microarray analysis. A 45-year-old patient with metastatic malignant melanoma was treated in third-line with indisulam (goal, E7070), a new chloroindolyl-sulphonamide cell-cycle inhibitor. The patient was treated weekly with a dose of 40 mg/m within a phase I study. On the basis of an amendment, the dose was escalated to 320 mg/m at maximum and de-escalated to 160 mg/m for long-term application in this individual patient. At the start of treatment the tumour burden consisted of two-in-transit-metastases, two further skin lesions, two cervical lymph nodes and four pulmonary metastases. Under a 2.5-year treatment with indisulam the tumour shrunk markedly although the objective response only reached stable disease. Lymph node biopsy revealed absence of vital melanoma cells. Therapy was stopped upon request of the patient. The gene expression profile indicated a profound transcriptional repression of subsets of genes involved in mitochondrial energy metabolism; namely NDUFB8, NDUFS1, NDUFV1, ACADVL and Homo sapiens clone 24408. The survival of this patient with metastatic melanoma lasted now 9 years, the progression-free interval 105 months. It can be assumed that this treatment effect is attributed to the down-regulating effect of indisulam on metabolic genes involved in energy production. Thus, knowledge on individual's tumour gene regulation may predict sensitivity and resistance to antitumoural agents.