title: Risk of oral and gastrointestinal mucosal injury among patients receiving selected targeted agents: a meta-analysis.
abstract: OBJECTIVE
  The purpose of this study was to estimate the risk and severity of oral and gastrointestinal mucosal toxicities associated with selected targeted agents.
  
  
  METHODS
  We searched the English-language literature in February 2011 for reports of randomized clinical trials comparing a FDA-approved targeted agent to a standard of care regimens. Long-term follow-up and secondary reports of trials were excluded, leaving 85 studies for analysis. Using meta-analytic methods, we calculated the relative risks of oral and gastrointestinal toxicities, adjusting for sample size using the inverse variance technique. For each targeted agent and each side effect, we calculated the number needed to harm, the number of patients that, if treated with the more toxic regimen, would produce one additional episode of the toxicity.
  
  
  RESULTS
  Oral mucositis was significantly more frequent among patients treated with bevacizumab, erlotinib, sorafenib, or sunitinib, although this difference was confined to low-grade mucositis. The clinical significance of these findings is unclear given its low incidence and mild severity. In contrast, diarrhea was significantly more frequent with most of the targeted agents studied, with adjusted relative risks between 1.5 and 4.5. An additional patient with diarrhea will be observed for every three to five patients treated with these targeted agents, compared with conventional regimens.
  
  
  CONCLUSIONS
  Oral mucosal toxicities occasionally complicate treatment with these targeted agents, but the clinical significance of this finding is not clear. Diarrhea is a hallmark of treatment with these targeted agents; this side effect should be carefully ascertained to permit early intervention and control.
authors: Department of Health Services Research, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Unit 1444, Houston, TX, 77030-4009, USA, lelting@mdanderson.org.
authors: Linda S
authors: LS
authors: Elting
authors: Yu-Chia
authors: YC
authors: Chang
authors: Pratibha
authors: P
authors: Parelkar
authors: Christine B
authors: CB
authors: Boers-Doets
authors: Marisol
authors: M
authors: Michelet
authors: Guido
authors: G
authors: Hita
authors: Tanya
authors: T
authors: Rouleau
authors: Catherine
authors: C
authors: Cooksley
authors: Josiah
authors: J
authors: Halm
authors: Madhuri
authors: M
authors: Vithala
authors: Paolo
authors: P
authors: Bossi
authors: Carmen
authors: C
authors: Escalante
authors: Michael T
authors: MT
authors: Brennan
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000453:epidemiology*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013280:Stomatitis / Q000139:chemically induced / Q000453:epidemiology*
chemical_list: D000970:Antineoplastic Agents
references: J Oncol. 2009;2009:567486
references: 19424511
references: Leukemia. 2009 Jun;23(6):1054-61
references: 19282833
references: J Clin Oncol. 2007 Oct 20;25(30):4743-50
references: 17909199
references: J Clin Oncol. 2008 May 20;26(15):2450-6
references: 18378568
references: Blood. 2005 Dec 1;106(12):3725-32
references: 16123223
references: N Engl J Med. 2009 Sep 3;361(10):947-57
references: 19692680
references: N Engl J Med. 2005 Jul 14;353(2):123-32
references: 16014882
references: N Engl J Med. 2004 Jul 29;351(5):501-5
references: 15282359
references: N Engl J Med. 2008 Jul 24;359(4):378-90
references: 18650514
references: Curr Opin Support Palliat Care. 2010 Mar;4(1):26-30
references: 20040879
references: N Engl J Med. 2006 Dec 7;355(23):2408-17
references: 17151364
references: Lancet Oncol. 2009 Jan;10(1):25-34
references: 19095497
references: J Clin Oncol. 2005 Jun 1;23(16):3676-85
references: 15738535
references: Blood. 2006 Nov 15;108(10):3295-301
references: 16873669
references: N Engl J Med. 2006 Dec 14;355(24):2542-50
references: 17167137
references: N Engl J Med. 2004 Jun 3;350(23):2335-42
references: 15175435
references: J Clin Oncol. 2005 Nov 1;23(31):7811-9
references: 16258083
references: J Clin Oncol. 2007 Apr 20;25(12):1539-44
references: 17442997
references: J Clin Oncol. 2010 Jul 10;28(20):3239-47
references: 20498403
references: J Clin Oncol. 2008 Jul 20;26(21):3523-9
references: 18640933
references: Blood. 2006 Dec 15;108(13):4003-8
references: 16946304
references: Oncology. 2010;78(5-6):376-81
references: 20798560
references: J Clin Oncol. 2005 May 20;23(15):3502-8
references: 15908660
references: Med Oncol. 2007;24(1):85-9
references: 17673816
references: Lancet. 2006 Oct 14;368(9544):1329-38
references: 17046465
references: Ann Oncol. 2008 Sep;19 Suppl 7:vii146-52
references: 18790937
references: Am Fam Physician. 2008 Feb 1;77(3):311-9
references: 18297955
references: J Clin Oncol. 2005 Feb 1;23(4):705-11
references: 15598978
references: J Clin Oncol. 2010 Jul 1;28(19):3191-8
references: 20516443
references: J Clin Oncol. 2007 May 20;25(15):1960-6
references: 17452677
references: Curr Opin Support Palliat Care. 2010 Mar;4(1):16-8
references: 20009759
references: J Clin Oncol. 2007 Apr 20;25(12):1545-52
references: 17442998
references: N Engl J Med. 2010 Jun 24;362(25):2380-8
references: 20573926
references: J Clin Oncol. 2009 Jun 1;27(16):2638-44
references: 19349549
references: Anticancer Drugs. 2006 Apr;17(4):401-9
references: 16549997
references: J Clin Oncol. 2009 Dec 20;27(36):6129-34
references: 19917839
references: J Clin Oncol. 2005 Jun 20;23(18):4117-26
references: 15867204
references: Blood. 2010 Sep 23;116(12):2040-5
references: 20548096
references: Oral Oncol. 2011 Jun;47(6):441-8
references: 21514211
references: Breast Cancer Res Treat. 2007 Mar;101(3):355-65
references: 16850247
references: Cancer. 2003 Oct 1;98(7):1531-9
references: 14508842
references: J Clin Oncol. 2007 Oct 20;25(30):4779-86
references: 17947725
references: J Clin Oncol. 2004 Jun 1;22(11):2184-91
references: 15169807
references: N Engl J Med. 2007 Dec 27;357(26):2666-76
references: 18160686
references: Lancet. 2007 Jan 6;369(9555):29-36
references: 17208639
references: N Engl J Med. 2008 Sep 11;359(11):1116-27
references: 18784101
references: J Clin Oncol. 2006 Jul 1;24(19):3121-7
references: 16754935
references: World J Gastroenterol. 2009 Jan 28;15(4):449-56
references: 19152449
references: Blood. 2008 Dec 15;112(13):4824-31
references: 18799723
references: Oncologist. 2007 Dec;12(12):1443-55
references: 18165622
references: J Clin Oncol. 2009 Mar 10;27(8):1280-9
references: 19171708
references: Lancet Oncol. 2010 Feb;11(2):121-8
references: 20022809
references: J Clin Oncol. 2008 Feb 20;26(6):863-9
references: 18281658
references: J Clin Oncol. 2010 Apr 1;28(10):1756-65
references: 20194844
references: Leukemia. 2009 Jan;23(1):153-61
references: 18818699
references: N Engl J Med. 2002 Jan 24;346(4):235-42
references: 11807147
references: J Clin Oncol. 2005 Sep 1;23(25):5892-9
references: 16043829
references: J Clin Oncol. 2009 Dec 1;27(34):5685-92
references: 19884557
references: J Clin Oncol. 2009 Mar 10;27(8):1227-34
references: 19188680
references: J Clin Oncol. 2008 Sep 10;26(26):4244-52
references: 18779611
references: J Clin Oncol. 2004 Mar 1;22(5):785-94
references: 14990633
references: J Clin Oncol. 2010 Feb 10;28(5):753-60
references: 20038730
references: Oral Oncol. 2009 Dec;45(12):1015-20
references: 19828360
references: JAMA. 2010 Nov 17;304(19):2154-60
references: 21081728
references: J Clin Oncol. 2005 Jul 1;23(19):4265-74
references: 15911866
references: Anticancer Drugs. 2005 Nov;16(10):1123-8
references: 16222155
references: J Clin Oncol. 2004 Sep 1;22(17):3485-90
references: 15337796
references: Ann Hematol. 2007 Feb;86(2):107-15
references: 17103169
references: Lung Cancer. 2010 Dec;70(3):301-7
references: 20400201
references: N Engl J Med. 2006 Feb 23;354(8):809-20
references: 16495393
references: Lancet Oncol. 2006 May;7(5):379-91
references: 16648042
references: Lancet. 2005 Oct 29-Nov 4;366(9496):1527-37
references: 16257339
references: Cancer Biother Radiopharm. 2007 Apr;22(2):194-9
references: 17600466
references: J Clin Oncol. 2010 Jul 20;28(21):3422-8
references: 20530280
references: N Engl J Med. 2009 Apr 2;360(14):1408-17
references: 19339720
references: Cancer. 2004 May 1;100(9 Suppl):2026-46
references: 15108223
references: Blood. 2005 Feb 15;105(4):1417-23
references: 15494430
references: Clin Cancer Res. 2007 Jan 1;13(1):228-33
references: 17200359
references: J Clin Oncol. 2009 May 1;27(13):2253-60
references: 19289623
references: Breast Cancer Res Treat. 2008 Dec;112(3):533-43
references: 18188694
references: N Engl J Med. 2003 Mar 13;348(11):994-1004
references: 12637609
references: Lancet. 2009 Mar 28;373(9669):1097-104
references: 19303137
references: Haematologica. 2009 Dec;94(12):1669-75
references: 19648168
references: Clin Cancer Res. 2010 Feb 15;16(4):1307-14
references: 20145166
references: Lancet Oncol. 2010 Jun;11(6):521-9
references: 20493771
references: Lancet. 2010 Jan 30;375(9712):377-84
references: 20113825
references: Clin Cancer Res. 2009 May 15;15(10):3583-90
references: 19417018
references: J Clin Oncol. 2007 May 20;25(15):1986-92
references: 17420513
references: Ann Oncol. 2008 Jul;19(7):1288-1292
references: 18349029
references: Nat Rev Clin Oncol. 2011 Dec 20;9(2):98-109
references: 22182972
references: Cancer. 2007 Mar 1;109(5):820-31
references: 17236223
references: J Clin Oncol. 2011 Mar 1;29(7):884-9
references: 21189384
references: J Clin Oncol. 2003 Jan 1;21(1):60-5
references: 12506171
references: N Engl J Med. 2005 Oct 20;353(16):1659-72
references: 16236737
references: Ann Oncol. 2008 Nov;19(11):1955-61
references: 18550575
references: J Clin Oncol. 2004 Mar 1;22(5):777-84
references: 14990632
references: N Engl J Med. 2001 Mar 15;344(11):783-92
references: 11248153
references: Lancet Oncol. 2008 Feb;9(2):105-16
references: 18226581
references: J Clin Oncol. 2005 Jun 1;23(16):3697-705
references: 15738537
references: J Clin Oncol. 2005 Mar 20;23(9):1984-92
references: 15668467
references: J Clin Oncol. 2009 Feb 10;27(5):663-71
references: 19114683
references: Ann Oncol. 2009 Dec;20(12):1985-92
references: 19567453
references: J Clin Oncol. 2009 Nov 20;27(33):5538-46
references: 19786658
references: J Clin Oncol. 2008 Dec 1;26(34):5544-52
references: 18955454
references: Leuk Lymphoma. 2009 Feb;50(2):211-5
references: 19197729
references: Support Care Cancer. 2007 May;15(5):483-90
references: 17103195
references: Lancet. 2008 Nov 22;372(9652):1809-18
references: 19027483
references: J Clin Oncol. 2005 Feb 1;23(4):792-9
references: 15681523
references: J Clin Oncol. 2009 Jul 10;27(20):3312-8
references: 19451442
references: J Clin Oncol. 2008 Apr 20;26(12):2013-9
references: 18421054
references: J Clin Oncol. 2010 Jun 10;28(17):2853-8
references: 20439641
references: Blood. 2005 Sep 1;106(5):1538-43
references: 15914552
references: J Clin Oncol. 2009 Oct 20;27(30):5080-7
references: 19738125
references: Blood. 2004 Nov 15;104(10):3064-71
references: 15284112
references: Int J Radiat Oncol Biol Phys. 2007 Jul 15;68(4):1110-20
references: 17398022
references: Cancer. 2004 May 1;100(9 Suppl):1995-2025
references: 15108222
references: Blood. 2004 Jun 15;103(12):4416-23
references: 14976046
references: J Clin Oncol. 2009 Aug 1;27(22):3584-90
references: 19487381
references: J Clin Oncol. 2008 Sep 10;26(26):4253-60
references: 18779612