title: Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside.
abstract: Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress.
authors: Department of Pathology, Institute of Ophthalmology, University College London, UK.
authors: M H
authors: MH
authors: Neale
authors: N
authors: N
authors: Myatt
authors: I A
authors: IA
authors: Cree
authors: C M
authors: CM
authors: Kurbacher
authors: A J
authors: AJ
authors: Foss
authors: J L
authors: JL
authors: Hungerford
authors: P N
authors: PN
authors: Plowman
mesh_terms: D000255:Adenosine Triphosphate / Q000302:isolation & purification; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives; D002830:Choroid Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D003561:Cytarabine / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008545:Melanoma / Q000737:chemistry / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D014410:Tumor Stem Cell Assay; D000093542:Gemcitabine
chemical_list: D003561:Cytarabine; D003841:Deoxycytidine; D000255:Adenosine Triphosphate; C018404:treosulfan; D002066:Busulfan; D017239:Paclitaxel; D000093542:Gemcitabine