Drug Topics - November 3, 2008 - (Page 6) 6 DRUG TOPICS NOVEMBER 3, 2008 www.drugtopics.com Of Interest to Pharmacists combination group. Dr. Yao concluded that treatment was active and well tolerated. Elesclomol, an investigational, injectable agent that triggers apoptosis in cancer cells by increasing oxidative stress, improved overall survival compared to paclitaxel monotherapy in patients with metastatic melanoma, according to Dr. Steven O’Day, Chief of Research and Director of the Melanoma Program at the Angeles Clinic and Research Institute in Santa Monica, Calif. In addition, there was a significant median progressionfree survival improvement with combined elesclomol and paclitaxel compared with paclitaxel monotherapy. The standard treatment for controlling symptoms in pancreatic neuroendocrine tumors (NETs) has been somatostatin analogues (octreotide and lanreotide). Results of a Phase II study of 160 patients with refractory pancreatic NETs randomized to everolimus (RAD001, 10 mg/d, n=115), an mTOR inhibitor with broad antitumor activity, given alone or in combination with octreotide (Sandostatin LAR [SL], ≤30 mg, q 28 d, n=45), showed the combination to more than double historical progression-free survival rates, according to Dr. James C. Yao, of MD Anderson Cancer Center in Houston. “With octreotide and lanreotide, we were in the era of symptom control. We’re now moving into an era of tumor control,” Yao said. The most notable advantage for the SL plus RAD001 combination was PFS at six months. By central review it was just more than nine months for RAD001 and nearly 13 months for RAD001 plus SL. Stable disease rates by central review were 68.7 percent for RAD001 and 77.8 percent for RAD001 plus SL, and by investigator assessment 66.1 percent and 71.1 percent respectively. For the primary endpoint of objective response rate (ORR, RECIST criteria), while investigator assessment placed the rate at 7 percent for RAD001 and 8.9 percent for RAD001 plus SL, central review placed them at 7.8 percent and 4.4 percent respectively. All responses were partial, Yao said. Stable disease rates were higher for the combination, according to both central (68.7 percent versus 77.8 percent) and investigator (66.1 percent versus 71.1 percent) review, as were clinical benefit rates (76.5 percent/82.2 percent and 73. percent/80 percent). Median overall survival was not reached in either group, and while median response duration was >10 months in the RAD001 group, it was not yet reached in the combination group. The most common grade three adverse events (AEs) with a suspected relationship to treatment were asthenia, fatigue, and thrombocytopenia, with 5 discontinuations for AEs in the RAD001 group and four in the Survival rates The study, a two-year follow up of a randomized Phase IIb trial of patients with stage IV metastatic melanoma, compared overall survival for elesclomol (213 mg/ m2) co-infused with paclitaxel (80mg/m2) in 53 patients versus paclitaxel monotherapy (80mg/ m2) in 29 patients in four-week cycles (three weeks of treatment and one week of rest) until disease progression. Participants had received prior chemotherapy once or not at all. Crossover to dual therapy was allowed for patients who progressed on monotherapy. Patients receiving elesclomol plus paclitaxel lived an average of four months longer than those on monotherapy (11.9 months versus nearly eight months). Also, two-year survival was higher in the elesclomol plus paclitaxel group (27 percent versus 21 percent). Among the 68 percent of paclitaxel patients who crossed over to dual therapy at time of progression, median survival was higher among the crossover patients compared to those who stayed on monotherapy after progression. O’Day reported also that the elesclomol plus paclitaxel regimen was tolerable and similar in safety to paclitaxel monotherapy. Serious adverse events in the dual therapy group, including neutropenia, back pain, fatigue, and neuropathy, were typical of those seen with paclitaxel monotherapy. Noting that advanced metastatic melanoma is a notoriously hard-to-treat disease, O’Day said, “This novel therapeutic approach may make melanoma, a largely chemoresistant disease, more sensitive to chemotherapy.” Phase III research is underway. Elesclomol is being developed through a collaboration between Synta Pharmaceuticals and GlaxoSmithKline. Patients receiving elesclomol plus paclitaxel lived an average of four months longer than those on monotherapy. http://www.drugtopics.com
Table of Contents Feed for the Digital Edition of Drug Topics - November 3, 2008 Drug Topics - November 3, 2008 Medication Errors: What to do When You Make a Mistake Stockholm Oncology Congress Reports on Several Studies Drug Topics - November 3, 2008 Drug Topics - November 3, 2008 - Drug Topics - November 3, 2008 (Page 1) Drug Topics - November 3, 2008 - Drug Topics - November 3, 2008 (Page 2) Drug Topics - November 3, 2008 - Medication Errors: What to do When You Make a Mistake (Page 3) Drug Topics - November 3, 2008 - Stockholm Oncology Congress Reports on Several Studies (Page 4) Drug Topics - November 3, 2008 - Stockholm Oncology Congress Reports on Several Studies (Page 5) Drug Topics - November 3, 2008 - Stockholm Oncology Congress Reports on Several Studies (Page 6)
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