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Originally published as JCO Early Release 10.1200/JCO.2008.21.2811 on March 2 2009 © 2009 American Society of Clinical Oncology.
How Many Patients and How Many Complications Does It Take to Decide if a Drug Is Safe to Use Before Surgery?Professor of Surgery, Mount Sinai School of Medicine, Director, Queens Cancer Center of Queens Hospital, New York, NY To the Editor: I eagerly read the article by Kesmodel et al1 entitled, "Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases," to clarify the safety of surgery in the increasing number of patients who are receiving bevacizumab (BV) before surgery. The authors reported 28% wound infections in the BV group versus 25% in the chemotherapy-without-BV group. Of the wound complications three patients in the BV group needed vacuum-assisted closure dressings as opposed to one in the chemo group. Another two patients in the BV group required operative management of the wound dehiscence, as opposed to none in the chemo group. The BV group had 9% other infectious complications versus 2% for the chemotherapy-only group. All the intra-abdominal collections were in the BV group. The one patient who died in the BV group died of sepsis. These authors concluded that there was no significant difference between these two groups, and that BV is safe to give. Is this accurate? Even in a matched randomized study these numbers might not be large enough to show significant differences, but in a retrospective matched control trial they are underpowered to make any statements about safety. When the wound infection rate is almost 30% and the infectious complications are one in one group and seven in the other group, this is clinically significant. If one adds the wound and infectious complications, over one third of the patients given BV had a significant infectious complication. I think a much broader, perhaps multi-institutional look at this question is necessary, so that we can get enough patients to know if the wound infection rate is three times as high in the BV group (as it was in the study by D'Angelica et al2) or if the infectious complications are 4.5 times as high as they were in this study. Before a prospective look at this question with at least 300 to 500 patients, I really don't think we should be publishing articles that say that BV is safe before surgery. A good illustration of the necessity of larger studies is the meta-analysis that was just published about the risk of venous thromboembolism with BV.3 After looking at randomized studies including 7,956 patients, the authors found a 33% increased risk of developing venous thromboembolism with BV than with a control. This once again shows that larger numbers are necessary to make safety statements about relatively rare complications. AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Kesmodel SB, Ellis LM, Lin E, et al: Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol 26:5254–5260, 2008. 2. D'Angelica M, Kornprat P, Gonen M, et al: Lack of evidence for increased operative morbidity after hepatectomy with perioperative use of bevacizumab: A matched case-control study. Ann Sug Oncol 14:759–765, 2007.[CrossRef][Medline] 3. Nalluri SR, Chu D, Kereszetes R, et al: Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients. JAMA 300:2277–2285, 2008.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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