THE EX-VIVO CHEMOSENSITIVITY PROFILE OF CHOROIDAL MELANOMA

Uveal melanoma has a high mortality rate and responds poorly to existi ng chemotherapy. We have therefore examined the sensitivity of uveal m elanoma to cytotoxic agents using an ex vivo chemosensitivity assay to determine whether some agents which have not been used for this tumor might have activity. An ATP-based tumor chemosensitivity assay (ATP-T CA) was used to determine the effect of nine cytotoxic drugs at multip le dilutions in 28 primary uveal melanoma specimens, Evaluable assay r esults from up to 16 tumors with each drug showed variable sensitivity to alkylating agents (three of nine with mitomycin C, one of 15 with cisplatin and seven of 15 with treosulfan), cytosine arabinoside (seve n of 16), paclitaxel (one of five) and doxorubicin (two of 16). No tum ors were sensitive to temozolomide, or 5-fluorouracil, and only one of 14 to vincristine. The combination of treosulfan with cytosine arabin oside resulted in enhanced tumor cell inhibition in three of five tumo rs tested. Combinations containing paclitaxel combined with doxorubici n or cisplatin showed some activity, but none achieved 100% inhibition and the results were similar to those obtained with paclitaxel alone, Uveal melanoma shows considerable heterogeneity of sensitivity to cyt otoxic drugs, with considerable resistance to most agents, matching cl inical experience. The results suggest that cytosine arabinoside or ge mcitabine plus treosulfan may be an active combination. Clinical trial s will commence shortly. The use of the AIP-TCA provides a method of t esting multiple agents and combinations in a way which would be otherw ise impossible in rare tumors such as uveal melanoma.