Dolastatin-10 in metastatic melanoma: A phase II and pharmokinetic trial of the california cancer consortium

Dolastatin-10 is a novel pentapeptide agent originally isolated from the ma rine mollusk Dolabella auricularia with a mechanism of antitumor activity t hat involves the inhibition of microtubule assembly. We performed a Phase I I trial of Dolastatin-10, 400 mug/m(2), in patients with advanced melanoma who had received no prior chemotherapy. Dolastatin-10 pharmokinetics were e valuated in a subset of patients following courses 1 and 2. Twelve patients were treated with a median of 2 cycles of Dolastatin-10, and no patient ex perienced an objective response. The only grade >2 toxicities were grade 3 neutropenia uncomplicated by infection, occurring in 4 patients following t he first treatment cycle. The total systemic clearance and volume of distri bution at steady-state were 2.61 +/- 1.9 L/h/m(2) and 28.4 +/- 13 L/m(2), r espectively. Due to prolonged terminal elimination, Dolastatin-10 plasma co ncentrations of greater than 1 nM were sustained for 24 h in all patients s tudied. Dolastatin-10 is unlikely to have substantial activity in the treat ment of melanoma.