Phase II, Randomized, Controlled, Double-Blinded Trial of Weekly Elesclomol Plus Paclitaxel Versus Paclitaxel Alone for Stage IV Metastatic Melanoma

• Published in: Journal of clinical oncology Vol. 27; no. 32; pp. 5452 - 5458
• Main Authors: O'DAY, Steven, GONZALEZ, Rene, LAWSON, David, WEBER, Robert, HUTCHINS, Laura, ANDERSON, Clay, HADDAD, Jonathan, KONG, Steven, WILLIAMS, Anthony, JACOBSON, Eric
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.11.2009
• Subjects: Adult; Aged; Aged, 80 and over; Anemia - chemically induced; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Constipation - chemically induced; Cross-Over Studies; Dermatology; Double-Blind Method; Drug Administration Schedule; Fatigue - chemically induced; Female; Humans; Hydrazines - administration & dosage; Hydrazines - adverse effects; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Medical sciences; Melanoma - drug therapy; Melanoma - pathology; Middle Aged; Nausea - chemically induced; Neoplasm Metastasis; Neoplasm Staging; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Paclitaxel - therapeutic use; Treatment Outcome; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Antineoplastic agent; Malignant tumor; Metastasis; Randomized controlled trial; Cancerology; Taxane derivatives; Phase II trial; Malignant melanoma; Paclitaxel; Advanced stage; Antimitotic; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.17.1579

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. 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). 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. 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.