Pharmacy & Therapeutics - November 2008 - (Page 669)

MEETING HIGHLIGHTS: ESMO and ASBMR Dr. Paz-Ares reported results of a multicenter study among 150 patients with advanced NSCLC. Patients had been randomly assigned, in a 2:1 ratio, to receive chemotherapy plus CP-751871 or chemotherapy alone. Chemotherapy was given as paclitaxel (Taxol, Bristol-Myers Squibb) at a dose of 200 mg/m2 plus carboplatin (Paraplatin, Bristol-Myers Squibb), with an area-under-the-curve (AUC) concentration of 6, plus CP-751871 at a dose of 10 mg/kg or 20 mg/kg. Enrolled patients had stage IIIB disease with malignant pleural effusion, stage IV disease, or measurable recurrent disease. Approximately 80% of patients (n = 120) had adenocarcinoma, and 20% (n = 30) had SCC. In both groups, chemotherapy was given every three weeks for up to six cycles. CP-751871 was given until disease progression. Patients with disease progression in the chemotherapy arm were eligible to receive the antibody alone or the combination. A post-study extension was conducted among the 30 patients with SCC. The primary endpoint was the objective response rate. Objective response rates were 54% with combination therapy and 41% with chemotherapy alone. In the SCC subpopulation, a dose response was noted for CP-751871, with objective response rates of 78% with 20 mg, 57% with 10 mg, and 46% with chemotherapy alone. The objective response rate for patients receiving CP-751871 alone was 78%. Among patients with adenocarcinoma, objective response rates were 57% with 20 mg, 38% with CP-751871, and 25% with chemotherapy alone. In patients with undifferentiated tumors, there was no benefit from CP-751871. “That’s consistent with the minimal IGF-1R expression seen in undifferentiated tumors,” Dr. Paz-Ares said. Progression-free sur vival improved, especially in those patients with SCC at the higher CP-751871 dose. Side effects were generally manageable, with grade 3 and 4 fatigue being the most common event in 10% of patients, hyperglycemia occurring in 20%, and neutropenia affecting 30%. Dr. Paz-Ares concluded that CP-751871 plus chemotherapy improved objective response rates better than chemotherapy alone. He underscored that robust responses, rarely observed with chemotherapy alone, were noted in patients with bulky squamous tumors. Phase 3 studies in refractory NSCLC are in progress. Elesclomol in Melanoma • Steven O’Day, MD, Chief of Research, and Director, Melanoma Program, Angeles Clinic and Research Institute, Santa Monica, Calif. An investigative injectable agent that increases oxidative stress in cancer cells and leads to apoptosis—Elesclomol (STA4783, Synta/GlaxoSmithKline)—was found to improve overall survival in patients with metastatic melanoma who received chemotherapy with paclitaxel. “This novel therapeutic approach,” stated Dr. O’Day, “may make melanoma, a largely chemoresistant disease, more sensitive to chemotherapy.” Noting that advanced metastatic melanoma is notoriously hard to treat, Dr. O’Day stated that the elesclomol/paclitaxel combination was tolerable in his study, with safety similar to that of paclitaxel alone. Neutropenia, back pain, fatigue, and neuropathy were the most common treatment-related effects. The study, a two-year follow-up of a randomized phase 2B trial of patients with stage IV metastatic melanoma, compared overall survival for elesclomol at a dose of 213 mg/m2 coinfused with paclitaxel at a dose of 80 mg/m2 in 53 patients against paclitaxel alone at a dose of 80 mg/m2 in 29 patients. Four-week cycles (three weeks of treatment and one week of rest) were administered until disease progression. Participants had received chemotherapy only one time or not at all. Crossing over to dual therapy was allowed for patients whose disease progressed with monotherapy. Patients receiving elesclomol plus paclitaxel lived an average of four months longer (11.9 months) than patients receiving paclitaxel monotherapy (7.8 months). Two-year survival was also higher in the elesclomol/paclitaxel patients (27%) than for the placebo patients (21%). Among the 68% of paclitaxel patients who crossed over to dual therapy at time of progression, median survival was higher among these patients (14.3 months) than among patients continuing monotherapy after disease progression (5.6 months). Dr. O’Day concluded that treatment of metastatic melanoma with elesclomol plus paclitaxel led to improved overall survival compared with paclitaxel alone. Phase 3 studies are ongoing. Association for the Study of Bone and Mineral Research Agents Producing Strong Increases in Bone Density Denosumab: Improving Bone Density Each year, the Association for the Study of Bone and Mineral Research (ASBMR) convenes clinical and experimental scientists involved in the study of bone and mineral metabolism.This year’s 30th annual meeting in Montreal, Canada, in September attracted 5,300 attendees from more than 60 countries.This article reviews two trials of investigative agents that increased bone mineral density in postmenopausal women. • Steven Cummings, MD, University of California, San Francisco, Calif. Denosumab (AMG-162, Amgen) is a fully human monoclonal antibody to RANKL (receptor activator for nuclear factor B ligand), which activates the osteoclast cells involved in breaking down bone. The FREEDOM Trial (Fracture REduction Evaluation of Denosumab in Osteoporosis every Six Months) enrolled 7,868 postmenopausal women (mean age, 64) from 214 centers in 32 countries. All patients had lumbar Vol. 33 No. 11 • November 2008 • P&T® 669

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Pharmacy & Therapeutics - November 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Heparin-Induced Thrombocytopenia Medication Utilization Patterns and Hypertension-Related Expenditures among Patients Who Were Switched From Fixed-Dose to Free-Combination Antihypertensive Therapy European Society for Medical Oncology and Association for the Study of Bone and Mineral Research Pharmaceutical Approval Update

Pharmacy & Therapeutics - November 2008

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