dacarbazine + bortezomib (Virginia Commonwealth University)

This investigational combination therapy consists of dacarbazine and bortezomib, developed and studied by Virginia Commonwealth University (VCU). Dacarbazine is a cytotoxic small molecule alkylating agent that functions as a prodrug, undergoing metabolic activation to form MTIC, which alkylates DNA and induces apoptosis. Bortezomib is a small molecule proteasome inhibitor that reversibly binds to the 26S proteasome, specifically the chymotrypsin-like activity of the beta5 subunit, leading to the stabilization of various regulatory proteins and the induction of programmed cell death. The combination was evaluated in a Phase I dose-escalation study for patients with advanced melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation (APUD) tumors, such as parathyroid carcinoma, small cell lung cancer, and carcinoid tumors. Preclinical data suggested that bortezomib could enhance the efficacy of dacarbazine by sensitizing tumor cells to DNA damage. The trial established recommended Phase II doses for weekly intravenous administration and observed clinical activity, including a durable complete response in a melanoma patient with a cKIT mutation.

Other names

dacarbazine and bortezomibDTIC + bortezomibDTIC + Velcade