Surgery News - November 2008 - (Page 20)

20 UROLOGY SURGERY NEWS • N O V E M B E R 2 0 0 8 Drug Combo Dropped PSA Levels in Metastatic Patients Although the combination was well tolerated by most patients, concerns about toxicity remain. B Y F R A N L O W RY Else vier Global Medical Ne ws n experimental combination of thalidomide, bevacizumab, and docetaxel reduced prostate-specific antigen by 50% or more in most men with PSA-positive metastatic castration-refractory prostate cancer disease during a small A phase II trial. Ninety percent of patients (52 of 58 men) met the 50% benchmark, and PSA levels declined by more than 75% in 44 patients, Dr. Yangmin M. Ning reported. Combining two antiangiogenesis agents with docetaxel (Taxotere) produced an overall response rate of 64%, as shown by improvement or disappearance of lesions on multiple bone scans in men who had measurable disease, said Dr. Ning of the Food and Drug Administration’s department of oncology drug products. Moreover, the median estimated progressionfree survival was 18 months, compared with a predicted median survival of 15 months—a result Dr. Ning called “very encouraging in this group of patients who have very unfavorable prognostic factors.” That angiogenesis has a vital role in the progression of metastatic castration-resistant prostate cancer provided the rationale NOW AVAILABLE The American College of Surgeons ATLS Program was developed to teach doctors one safe, reliable method for assessing and initially managing the trauma patient. The course teaches an organized approach for evaluation and management of seriously injured patients and offers a foundation of common knowledge for all members of the trauma team. The emphasis is on the critical “ﬁrst hour” of care, focusing on initial assessment, lifesaving intervention, reevaluation, stabilization, and, when needed, transfer to a trauma center. The 8th edition has been redesigned for readability and to improve comprehension and retention of knowledge. It features new, up-to-date technical content and references and includes a DVD with skills from the course demonstrated in video segments. Price: $100 each. To obtain an ATLS for Doctors Student Course Manual, visit the American College of Surgeons online publication catalog at https://web2.facs.org/timssnet464/acspub/frontpage.cfm?product_class=trauma for combining the two mechanistically different antiangiogenic agents, he said. Investigators wanted to see whether blocking multiple angiogenic pathways would enhance the antitumor effects of docetaxel. Patients with progressive disease and no prior chemotherapy or antiangiogenic therapy received 75 mg/m2 of docetaxel plus 15 mg/kg of bevacizumab (Avastin) on day 1, and thalidomide and prednisone daily during a 21-day cycle. Enoxaparin (Lovenox) was administered prophylactically once a day to prevent thrombosis. A median of 15 cycles was delivered (range, 2-51). All study participants had poor prognostic factors. Roughly 70% had Gleason scores of 8-10, and 80% had a PSA doubling time of less than 3 months, with a median of 48 days. The predicted median survival for this patient population was 15 months. The combination was tolerated well by most patients, Dr. Ning said. DeThis combination is highly active in spite enoxaparin prophylaxis, three metastatic cases of thrombosis castrationrefractory prostate occurred. All resolved with anticocancer. agulation therapy. DR. NING Two patients had gastrointestinal perforation, and one had esophageal perforation. All had good recovery after repair. One patient experienced osteonecrosis of the jaw. When asked about this adverse event during the question-and-answer period, Dr. Ning said he and his coinvestigators were vigilant about looking for this complication, and this heightened vigilance might have been why it was noted. “Our findings demonstrate that this triple combination is highly active in patients with metastatic castration-refractory prostate cancer, and warrants further study in future trials,” he said. Commenting on the study, Dr. William Kevin Kelly of Yale University, New Haven, Conn., said he was impressed by the PSA decline seen in 90% of the patients, but he had concerns about toxicity. “The rate of syncope was 12%; febrile neutropenia, 10%; thrombosis, 5% despite prophylaxis with enoxaparin; GI perforation, 3%; hemorrhage, 5%; and there was a 2% incidence of osteonecrosis of the jaw. These are high rates of toxicity,” he said. He added that awareness of osteonecrosis of the jaw might be greater now than previously, but it remains a concern. Limiting the number of treatment cycles or using an intermittent treatment approach might be ways to decrease toxicity, as might replacing thalidomide with lenalidomide (Revlimid), he said. Dr. Ning reported no conflicts of interest. Dr. Kelly disclosed relationships with Onyx Pharmaceuticals Inc., Sanofi-Aventis, Medarex Inc., Bristol-Myers Squibb Co., ImClone Systems Inc., CuraGen Corp., TopoTarget A/S, Cougar Biotechnology Inc., Genentech Inc., and Centocor Inc. ■ https://web2.facs.org/timssnet464/acspub/frontpage.cfm?product_class=trauma

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Surgery News - November 2008 Contents News:�Without a Stitch The 20/20 Vision:�Med School Mix News From the College:�New President General Surgery: Diabetes Debate

Surgery News - November 2008

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