title: Treosulfan is an effective alkylating cytostatic for malignant melanoma in vitro and in vivo.
abstract: The therapy of metastatic malignant melanoma is limited by poor responses and short overall survival. Thus it remains an important issue to identify and test potential new drugs in this disease. This study was performed to examine the effects of the bifunctional alkylating cytostatic treosulfan in vitro. Using an in vitro microplate ATP bioluminescence tumour chemosensitivity assay (ATP-TCA) five highly chemoresistant melanoma cell lines and melanoma cells freshly isolated from metastases surgically resected from stage IV melanoma patients (n = 10) were incubated with treosulfan. Three cell lines and eight of the 10 tested tumour cells isolated from melanoma metasteses showed tumour growth inhibition >50% after incubation with treosulfan. Therefore, 14 patients with rapidly progressing stage IV malignant melanoma who had been pretreated with at least one standard chemotherapy regimen received treosulfan. In this population of patients with highly refractory advanced melanoma, one complete remission (7.1%), two partial remissions (14.3%) and three cases of stable disease (21.4%) were observed. The median survival time for all the patients measured from the beginning of treosulfan treatment was 9 months, and the median overall survival was 17 months. Except for two patients who developed grade 3 leucopenia, only moderate side effects were observed. Therefore, we conclude that treosulfan was well tolerated in this small series of patients and seems to be a promising alkylating cytostatic for the treatment of metastatic melanoma. Further studies are warranted to test these findings.
authors.affiliation: Department of Dermatology, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Neuber
authors.forename: A
authors.initials: A
authors.lastname: tom Dieck
authors.forename: N
authors.initials: N
authors.lastname: Blödorn-Schlicht
authors.forename: G
authors.initials: G
authors.lastname: Itschert
authors.forename: C
authors.initials: C
authors.lastname: Karnbach
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology* / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D010865:Pilot Projects; D014407:Tumor Cells, Cultured
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000255:Adenosine Triphosphate; C018404:treosulfan; D002066:Busulfan