Efficacy of Dacarbazine (DTIC) in preventing metastases arising from intraocular melanomas in mice

At present there are no chemotherapeutic agents that have been proven to be effective in either preventing or retarding the progression of metastases arising from uveal melanomas in human subjects. Dacarbazine (DTIC), the single most effective chemotherapeutic agent in the treatment of cutaneous melanoma, is a potentially useful therapeutic modality for use as an antimetastatic agent in uveal melanoma. However, DTIC has not been evaluated for its ability to impede metastases originating from intraocular melanomas. The present study assessed the antimetastatic efficacy of DTIC in a murine intraocular melanoma model. The results indicate that treatment with DTIC resulted in sharp reductions in the number of spontaneous metastases and a significant prolongation of survival time. Dose-response studies indicated that exceedingly high doses of DTIC were necessary to produce antimetastatic effects even when drug treatment was combined with the calcium channel blocker verapamil. Collectively, the results indicate that DTIC can be an effective adjunctive therapeutic agent when administered at the time of enucleation of the melanoma-containing eye but is ineffectual if administered subsequent to surgery.