PURPOSE Elesclomol is a novel,
small-molecule,
oxidative stress inducer believed to exert
selective cytotoxicity by increasing
intracellular concentrations of
reactive oxygen species, which results in
cell death via
mitochondrial apoptosis. We evaluated whether the addition of elesclomol to weekly
paclitaxel could improve efficacy in patients with stage IV
metastatic melanoma. PATIENTS AND METHODS We
randomly assigned patients with
metastatic melanoma, measurable disease, and one or fewer
prior chemotherapy regimens to elesclomol 213 mg/m(2) plus
paclitaxel 80 mg/m(2) (E + P) or to
paclitaxel 80 mg/m(2) alone at a 2:1 ratio; regimens were given as a 1-hour
intravenous infusion weekly, during 3 of every 4 weeks until disease progression per Response Evaluation Criteria in
Solid Tumors or death occurred. Patients who experienced progression were unblended, and patients on
paclitaxel alone were permitted to cross over to E + P. The primary efficacy end point was progression-free survival (PFS); secondary end points were
response rate (RR),
toxicity, and overall survival (OS; analyzed post hoc). Results At 21 US sites, 53 patients were
randomly assigned to E + P, and 28 patients were
randomly assigned to
paclitaxel. The addition of elesclomol to
paclitaxel yielded a doubling of
median PFS (112 v 56 days) and a 41.7% risk reduction for disease progression/death (
hazard ratio, 0.583; P = .035). Respective RRs for the E + P and
paclitaxel groups were 15% and 3%;
median OS was 11.9 v 7.8 months. Of patients on
paclitaxel alone, 19 (68%) of 28 crossed over to E + P after they experienced progression. Weekly E + P was well tolerated. CONCLUSION E + P resulted in a
statistically significant doubling of
median PFS, with an acceptable
toxicity profile and encouraging OS. A multinational,
phase III trial (SYMMETRY) of E + P compared with
paclitaxel alone in
metastatic melanoma has closed.
