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JAN 2018 Journal of The Society of Physicians of Hong Kong | 1

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2 | Journal of The Society of Physicians of Hong Kong JAN 2018

Key points• This review focuses on the epide-

miology, definitions, complications, management strategies and future research perspectives for metabolic syndrome (MetSyn).

• The prevalence of MetSyn is rising globally and has contributed substan-tially to public health burden in terms of morbidity and mortality. Reported prevalence of MetSyn varies widely, depending on the study characteristics, population selection, and diagnostic criteria adopted.

• The frequent amendments to the criteria of diagnosing MetSyn over time make it difficult to determine the regional variations and temporal trends in its prevalence.

• MetSyn increases the risk of developing type 2 diabetes mellitus, cardiovascular diseases, and other complications.

• Effective lifestyle modification approaches for MetSyn include weight loss, diet, and exercise.

• The manipulation of the gut micro-biota could be a promising therapy for MetSyn. Future research should explore extensively into the pathways by which gut microbiota influence the metabolism of the host to develop more effective approaches.


References1. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet

2005;365:1415–1428.2. Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome:

prevalence in worldwide populations. Endocrinol Metab Clin North Am 2004;33:351–375.

3. Desroches S, Lamarche B. The evolving definitions and increasing prevalence of the metabolic syndrome. Appl Physiol Nutr Metab 2007;32:23–32.

4. van der Berg JD, Stehouwer CD, Bosma H, et al. Associations of total amount and patterns of sedentary behaviour with type 2 diabetes and the metabolic syndrome: The Maastricht Study. Diabetologia 2016;59:709–718.

5. Li JB, Wang X, Zhang JX, et al. Metabolic syndrome: prevalence and risk factors in southern China. J Int Med Res 2010;38:1142–1148.

6. Chillaron JJ, Flores-Le-Roux JA, Goday A, et al. [Metabolic syndrome and type-1 diabetes mellitus: prevalence and associated factors]. Rev Esp Cardiol 2010;63:423–429.

7. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356–359.

8. Goldstein MR, Mascitelli L, Pezzetta F. On treating metabolic syndrome: emphasise lifestyle change. The Lancet Oncology 2010;11:415.

9. Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539–553.

10. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16:442–443.

11. Einhorn D, Reaven GM, Cobin RH, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract 2003;9:237–252.

12. Expert Panel on Detection E, Treatment of High Blood Cholesterol in A. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486–2497.

13. Alberti KG, Zimmet P, Shaw J, Group IDFETFC. The metabolic syndrome--a new worldwide definition. Lancet 2005;366:1059–1062.

14. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735–2752.

15. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640–1645.

16. Chinese Diabetes Society: Metabolic Syndrome Cooperative Study Group. The suggestion about metabolic syndrome from Chinese diabetes society. Chin J Diabetes Mellitus 2004;12:156–161.

17. Weng J, Ji L, Jia W, et al. Standards of care for type 2 diabetes in China. Diabetes Metab Res Rev 2016;32:442–458.

18. Joseph J, Svartberg J, Njolstad I, Schirmer H. Risk factors for type 2 diabetes in groups stratified according to metabolic syndrome: a 10-year follow-up of the Tromso Study. Eur J Epidemiol 2011;26:117–124.

19. Hanefeld M, Karasik A, Koehler C, Westermeier T, Chiasson JL. Metabolic syndrome and its single traits as risk factors for diabetes in people with impaired glucose tolerance: the STOP-NIDDM trial. Diab Vasc Dis Res 2009;6:32–37.

20. Salminen M, Kuoppamaki M, Vahlberg T, Raiha I, Irjala K, Kivela SL. Metabolic syndrome defined by modified International Diabetes Federation criteria and type 2 diabetes mellitus risk: a 9-year follow-up among the aged in Finland. Diab Vasc Dis Res 2013;10:11–16.

21. Salazar MR, Carbajal HA, Espeche WG, et al. Identifying cardiovascular disease risk and outcome: use of the plasma triglyceride/high-density lipoprotein cholesterol concentration ratio versus metabolic syndrome criteria. J Intern Med 2013;273:595–601.

22. Chang ST, Chu CM, Pan KL, et al. Prevalence and cardiovascular disease risk differences for erectile dysfunction patients by three metabolic syndrome definitions. Int J Impot Res 2011;23:87–93.

23. Liu C, Feng M, Fang XH, et al. [Metabolic syndrome is an independent risk factor for cardiovascular disease events in patients with ischemic stroke]. Zhonghua Xin Xue Guan Bing Za Zhi 2011;39:358–362.

24. Nitta K. Possible link between metabolic syndrome and chronic kidney disease in the development of cardiovascular disease. Cardiol Res Pract 2010;2011.

25. Lucero D, Zago V, Lopez GI, et al. Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome. Clin Chim Acta 2011;412:143–147.

26. Baldani DP, Skrgatic L, Ougouag R. Polycystic Ovary syndrome: important underrecognised cardiometabolic risk factor in reproductive-age women. Int J Endocrinol 2015;2015:786362.

27. Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 2012;35:2402–2411.

28. Wong ND. Intensified screening and treatment of the metabolic

syndrome for cardiovascular risk reduction. Prev Cardiol 2005;8:47–52; quiz 3–4.

29. Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014;2014:943162.

30. Deen D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875–2882.

31. Festi D, Schiumerini R, Eusebi LH, Marasco G, Taddia M, Colecchia A. Gut microbiota and metabolic syndrome. World J Gastroenterol 2014;20:16079–16094.

32. D'Aversa F, Tortora A, Ianiro G, Ponziani FR, Annicchiarico BE, Gasbarrini A. Gut microbiota and metabolic syndrome. Intern Emerg Med 2013;8 Suppl 1:S11–15.

33. Chassaing B, Gewirtz AT. Gut microbiota, low-grade inflammation, and metabolic syndrome. Toxicol Pathol 2014;42:49–53.

34. Cavalcante-Silva LH, Galvao JG, da Silva JS, de Sales-Neto JM, Rodrigues-Mascarenhas S. Obesity-driven gut microbiota inflammatory pathways to metabolic ayndrome. Front Physiol 2015;6:341.

35. Jiang Z, Zhao M, Zhang H, Li Y, Liu M, Feng F. Antimicrobial emulsifier - glycerol monolaurate induces metabolic syndrome, gut microbiota dysbiosis and systemic low-grade inflammation in low-fat diet fed mice. Mol Nutr Food Res 2017.

36. Parekh PJ, Arusi E, Vinik AI, Johnson DA. The role and influence of gut microbiota in pathogenesis and management of obesity and metabolic syndrome. Front Endocrinol (Lausanne) 2014;5:47.

37. He M, Shi B. Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics. Cell Biosci 2017;7:54.

38. O'Connor S, Chouinard-Castonguay S, Gagnon C, Rudkowska I. Prebiotics in the management of components of the metabolic syndrome. Maturitas 2017;104:11–18.

39. Staudacher HM, Cox SR. Editorial: metabolic adaptation of colonic microbiota to galactooligosaccharides - good news for prebiotics in irritable bowel syndrome? Aliment Pharmacol Ther 2017;45:1005–1006.

40. Costabile A, Walton GE, Tzortzis G, Vulevic J, Charalampopoulos D, Gibson GR. Development of a bread delivery vehicle for dietary prebiotics to enhance food functionality targeted at those with metabolic syndrome. Gut Microbes 2015;6:300–309.

41. de Cossio LF, Fourrier C, Sauvant J, et al. Impact of prebiotics on metabolic and behavioral alterations in a mouse model of metabolic syndrome. Brain Behav Immun 2017;64:33–49.

42. Peluso I, Romanelli L, Palmery M. Interactions between prebiotics, probiotics, polyunsaturated fatty acids and polyphenols: diet or supplementation for metabolic syndrome prevention? Int J Food Sci Nutr 2014;65:259–267.


References1. Korrapati P, Ciolino J, Wani S, et al. The efficacy of peroral cholangioscopy

for difficult bile duct stones and indeterminate strictures: a systematic review and meta-analysis. Endosc Int Open 2016;4:E263–E275.

2. Brewer Gutierrez OI, Bekkali NLH, Raijman I, et al. Efficacy and safety of digital single-operator cholangioscopy for difficult biliary stones. Clin Gastroenterol Hepatol 2017. Oct 24. [Epub ahead of print]

3. Huang SW, Lin CH, Lee MS, et al. Residual common bile duct stones on direct peroral cholangioscopy using ultraslim endoscope. World J Gastroenterol 2013;19:4966–4972.

4. Xie C, Aloreidi K, Patel B, et al. Indeterminate biliary strictures: a simplified approach. Expert Rev Gastroenterol Hepatol 2017. Oct 23:1–11. [Epub ahead of print]

5. Almadi MA, Barkun A, Martel M. Plastic vs. self-expandable metal stents for palliation in malignant biliary obstruction: A series of meta-analyses. Am J Gastroenterol 2017;112:260–273.

6. Kallis Y, Phillips N, Steel A et al. Analysis of endoscopic radiofrequency ablation of biliary malignant strictures in pancreatic cancer suggests potential survival benefit. Dig Dis Sci 2015;60:3449–3455.

7. Laquière A, Boustière C, Leblanc S et al. Safety and feasibility of

endoscopic biliary radiofrequency ablation treatment of extrahepatic cholangiocarcinoma. Surg Endosc 2016;30:1242–1248.

8. Sofi AA, Khan MA, Das A, et al. Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc 2017. Nov 3. [Epub ahead of print]

9. Moole H, Tathireddy H, Dharmapuri S, et al. Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis. World J Gastroenterol 2017; 23:1278–1288.

10. ASGE Standards of Practice Committee; Maple JT, Ben-Menachem T, Anderson MA, et al. The role of endoscopy in the evaluation of suspected choledocholithiasis. Gastrointest Endosc 2010;71:1–9.

11. He H, Tan C, Wu J, et al. Accuracy of ASGE high-risk criteria in evaluation of patients with suspected common bile duct stones. Gastrointest Endosc 2017;86:525–532.

12. Meeralam Y, AI-Shammari K, Yaghoobi M. Diagnostic accuracy of EUS compared with MRCP in detecting choledocholithiasis: a meta-analysis of diagnostic test accuracy in head-to-head studies. Gastrointest Endosc 2017;86:989–993.

13. De Castro VL, Moura EG, Chaves DM, et al. Endoscopic ultrasound versus magnetic resonance cholangiopancreatography in suspected

choledocholithiasis: A systematic review. Endosc Ultrasound 2016;5:118–128.

14. Anderloni A, Ballarè M, Pagliarulo M, et al. Prospective evaluation of early endoscopic ultrasonography for triage in suspected choledocholithiasis: results from a large single centre series. Dig Liver Dis 2014;46:335–339.

15. Lee YT, Chan FK, Leung WK, et al. Comparison of EUS and ERCP in the investigation with suspected biliary obstruction caused by choledocholithiasis: a randomized study. Gastrointest Endosc 2008;67:660–668.

16. Patel R, Ingle M, Choksi D, et al. Endoscopic ultrasonography can prevent unnecessary diagnostic endoscopic retrograde cholangiopancreatography even in patients with high likelihood of choledocholithiasis and inconclusive ultrasonography: Results of a prospective study. Clin Endosc 2017;50:592–597.

17. DeBenedet AT, Elmunzer BJ, McCarthy ST, et al. Intraprocedural quality in endoscopic retrograde cholangiopancreatography: a meta-analysis. Am J Gastroenterol 2013;108:1696–1704.

18. Chan JH, Teoh AY. Current status of endoscopic gallbladder drainage. Clin Endosc 2017. Nov 17. [Epub ahead of print]

19. Minaga K, Kitano M. Recent advances in endoscopic ultrasound-guided biliary drainage. Dig Endosc 2017. Jun 28. [Epub ahead of print]


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HR=0.63; 95% CI, 0.50–0.79

References1. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines

for the management of patients with metastatic colorectal cancer. Ann Oncol 2016;27:1386–1422.

2. Cunningham D, Lang I, Marcuello E, et al; AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013;14:1077–1085.

3. Tebbutt NC, Wilson K, Gebski VJ, et al. Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study. J Clin Oncol 2010;28:3191–3198.

4. Simkens LH, van Tinteren H, May A, et al. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet 2015;385:1843–1852.

15 positive pivotal trials across 7 cancer types1-15

The Power of Proof

Anti-angiogenesis with Avastin Roche®

Abbreviated Prescribing Information – Avastin Roche Injection 100mg/4 ml (bevacizumab) Indications: Metastatic colorectal cancer (mCRC) - in combination with fluoropyrimidine-based chemotherapy. Metastatic breast cancer (mBC) - in combination with paclitaxel for 1st line mBC. Non-small cell lung cancer (NSCLC) - in addition to platinum-based chemotherapy for 1st line treatment of unresectable, advanced, metastatic or recurrent NSCLC other than predominantly squamous cell histology; in combination with erlotinib, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations. Advanced and/or metastatic renal cell carcinoma (mRCC) - in combination with interferon alfa-2a. Glioblastoma - for the treatment of glioblastoma with progressive disease following prior therapy as a single agent. Epithelial ovarian, fallopian tube or primary peritoneal cancer - in combination with carboplatin and paclitaxel for front-line treatment of advanced (FIGO stage III B, III C & IV) cancer; in combination with carboplatin and gemcitabine for 1st recurrence of platinum-sensitive cancer who have not received prior bevacizumab therapy / other VEGF inhibitors / receptor-targeted agents; in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents. Cervical Cancer - in combination with paclitaxel and cisplatin or, alter-natively, paclitaxel and topotecan in patients who cannot receive platinum therapy, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.Dosage & Administration: Physicians experienced in antineoplastic medicines should supervise Avastin Roche administration. Continue treatment until progression of underlying disease or unacceptable toxicity (except for Glioblastoma). mCRC - 5mg/kg or 10mg/kg every 2 weeks; or 7.5mg/kg or 15mg/kg Q3wks. mBC - 10mg/kg Q2wks; or 15mg/kg Q3wks. NSCLC (First-line treatment of non-squamous NSCLC in combination with platinum-based chemotherapy) - 7.5mg/kg or 15mg/kg Q3wks in addition to platinum-based chemotherapy for up to 6 cycles, then as monotherapy. mRCC/Glioblastoma - 10mg/kg once Q2wks; NSCLC (First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib) - 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion in addition to erlotinib. Epithelial ovarian/Fallopian tube/Primary peritoneal cancer – front-line: 15mg/kg once Q3wks in addition to carboplatin and paclitaxel for up to 6 cycles, then as monotherapy; platinum-sensitive recurrent disease: 15mg/kg once Q3wks in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles, then as monotherapy; platinum-resistant recurrent disease: 10mg/kg once every 2 weeks in combination with paclitaxel or pegylated liposomal doxorubicin or 15mg/kg with topotecan (given on days 1-5, every 3 weeks) once every 3 weeks. Cervical cancer – 15mg/kg once every 3 weeks in combination with one of the following regime: paclitaxel and cisplatin or paclitaxel and topotecan. Method of administration: initial dose: IV infusion over 90 mins; if well tolerated, second dose: IV infusion over 60 mins; if well tolerated, subsequent doses: IV infusion over 30 mins. Do not administer as IV push or bolus or mix with glucose. Dose reduction for adverse events not recommended. If indicated, discontinue or temporarily suspend therapy. No recommendations for use in children or adolescents (<18 years old). No dose adjustment in the elderly.Contraindications: Hypersensitivity to bevacizumab or any of the excipients, Chinese hamster ovary cell products and other recombinant human or humanised antibodies. Pregnancy.Warnings & Precautions: Trade name of administered product should be clearly recorded to improve traceability. Gastrointestinal (GI) perforation: increased risk for development of GI and gall bladder perforation; intra-abdominal inflammatory process may be a risk factor in patients with metastatic carcinoma of the colon or rectum; discontinue therapy permanently in patients who develop GI perforation. Fistulae: permanently discontinue in tracheoesophageal or any Grade 4 fistula, consider discontinuation in non-GI fistula. Patients treated for persistent, recurrent, or metastatic cervical cancer are at increased risk of fistulae between the vagina and any part of the GI tract. Wound healing: do not initiate for at least 28 days following major surgery or until surgical wound is fully healed; withhold for elective surgery. Necrotizing Fasciitis: cases including fatality have been reported, discontinue therapy and initiate appropriate treatment. Hypertension: control pre-existing hypertension prior to treatment. Monitor blood pressure during therapy and control hypertension with standard antihypertensive therapy; the use of diuretics is not advised in patients on cisplatin-based chemotherapy. Permanently discontinue if hypertension remains uncontrolled or for hypertensive crisis/encephalopathy. Posterior Reversible Encephalopathy Syndrome (PRES): signs include: seizures, headache, altered mental status, visual disturbance or cortical blindness with/without associated hypertension. Confirm by brain imaging, treat symptoms and discontinue Avastin Roche once developed. Proteinuria: Patients with a history of hypertension may be at increased risk; monitoring of proteinuria by dipstick urinalysis is recommended prior to and during therapy. Permanently discontinue therapy if Grade 4 proteinuria develops. Arterial thromboembolism: including cerebrovascular accidents, transient ischaemic attacks and myocardial infarctions, especially if with prior history, diabetes or in elderly. Permanently discontinue therapy if arterial thromboembolic events develop. Venous thromboembolism: including pulmonary embolism; discontinue in Grade 4 pulmonary embolism and closely monitor where ≤Grade 3. Patients treated for persistent, recurrent, or metastatic cervical cancer in combination with paclitaxel and cisplatin may be at increased risk of venous thromboembolic events. Haemorrhage, especially tumour-associated haemorrhage: discontinue permanently if Grade 3/4. Risk of CNS haemorrhage in patients with untreated CNS metastases has not been prospectively evaluated. Monitor for signs and symptoms of CNS bleeding and discontinue Avastin Roche in cases of intracranial bleeding. Caution in patients with congenital bleeding diathesis, acquired coagulopathy or during anticoagulant therapy. Serious/fatal pulmonary haemorrhage/haemoptysis in NSCLC: do not use where recent significant pulmonary haemorrhage/haemoptysis (>1/2 teaspoon of red blood). Congestive Heart Failure (CHF): caution in patients with clinically significant cardiovascular disease or pre-existing CHF; most of the patients who experienced CHF had metastatic breast cancer and had received previous treatment with anthracyclines, prior radiotherapy to the left chest wall or other risk factors for CHF. Neutropenia and infections: fatal infection with or without severe neutropenia in combination with myelotoxic chemotherapy, mainly seen in platinum- or taxane-based therapies for NSCLC and mBC. Hypersensitivity: Close observation during and following drug administration. Infusion should be discontinued and appropriate medical therapies should be administered if a reaction occurs. Osteonecrosis of the jaw (ONJ):

concomitant treatment with i.v. bisphosphonates and invasive dental procedures are identified risk factors to ONJ; patients who have previously received or are receiving i.v. bisphosphonates should avoid invasive dental procedures. Intavitreal use: Avastin Roche is not formulated for intravitreal use. Eye disorders: including endophthalmitis, intraocular inflammation, retinal detachment, retinal pigment epithelial tear, intraocular pressure increased and intraocular haemorrhage have been reported following unapproved intravitreal use of Avastin Roche compounded from vials approved for cancer patients, some reactions results in visual loss. Systemic effect following intravitreal use: reduction of VEGF conc. has been demonstrated, non-ocular haemorrhages and ATE has been reported. Ovarian Failure / Fertility: Fertility preservation strategies should be discussed with women of child-bearing potential prior to treatment.Drug Interactions: No clinically relevant pharmacokinetic interaction between co-administered chemotherapy and Avastin Roche. Safety and efficacy with concomitant radiotherapy has not been established. Microangiopathic haemolytic anaemia has been reported when Avastin Roche was used with sunitinib malate; hypertension, elevated creatinine and neurological symptoms were also observed. Increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia have been observed in patients on platinum- or taxane-based therapies in the treatment of NSCLC and mBC. No interaction studies have been performed between EGFR monoclonal antibody and bevacizumab chemotherapy regimens, decreased PFS/OS and increased toxicity was observed in phase III studies. Use in Pregnancy & Lactation: Avastin Roche should not be used during pregnancy because no adequate & well-controlled data. Inhibition of foetal angiogenesis is anticipated. Avastin Roche may have temporary adverse effect on female fertility and cause ovarian failure. Women with childbearing potential must use effective contraception during and for up to 6 months after treatment. Discontinue breast-feeding during treatment and for at least 6 months after last dose.Undesirable Effects: For full listings please refer to the Avastin Roche package insert. Most serious reactions: GI perforation; haemorrhage including pulmonary haemorrhage/haemoptysis and arterial thromboembolism. Serious reactions, very common: Febrile neutropenia, leucopenia, thrombocytopenia, neutropenia, peripheral sensory neuropathy, hypertension, diarrhoea, nausea, vomiting, asthenia and fatigue. Serious reactions, common: Sepsis, abscess, infection, anaemia, dehydration, cerebrovascular accident, syncope, somnolence, headache, congestive cardiac failure, supraventricular tachycardia, arterial thromboembolism, deep vein thrombosis, haemorrhage, pulmonary embolism, dyspnoea, hypoxia, epistaxis, intestinal perforation and obstruction, ileus, abdominal pain, GI disorder, stomatitis, palmar-plantar erythrodysaesthesia syndrome, muscular weakness, myalgia, arthralgia, proteinuria, urinary tract infection pain, lethargy and mucosal inflammation. All grades, very common: Anorexia, dysgeusia, headache, dysarthria, eye disorder, lacrimation increased, hypertension, dyspnoea, epistaxis, rhinitis. constipation, stomatitis, rectal haemorrhage, diarrhoea, ovarian failure, exfoliative dermatitis, dry skin, skin discolouration, arthralgia, proteinuria, pyrexia, asthenia, pain and mucosal inflammation. Other reactions: Hypertensive encephalopathy. PRES (rare). Renal thrombotic Microangiopathy manifested as proteinuria. Nasal septum perforation. Pulmonary hypertension. Dysphonia. GI ulcer. Gall bladder perforation. Hypersensitivity. Necrotizing fasciitis. ONJ, Non-mandibular osteonecrosis. Laboratory abnormalities and Post Marketing – refer to package insert.Date of preparation: August 2016Full prescribing information should be viewed prior to prescribing

References: 1. Hurwitz H, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-42. 2. Giantonio BJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol. 2007 Apr 20;25(12):1539-44. 3. Saltz L, et al. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. 4. Bennouna J, et al. Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol. 2013 Jan;14(1):29-37. 5. Sandler A, et al. Paclitaxel–carboplatin alone or with bevacizumab for non–small-cell lung cancer. N Engl J Med. 2006;355:2542-50. 6. Reck M, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009 Mar 10;27(8):1227-34. 7. Miller K, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666-76. 8. Robert NJ, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011 Apr 1;29(10):1252-60. 9. Friedman HS, et al. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. 10. Escudier B, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007 Dec 22;370(9605):2103-11. 11. Burger RA, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011;365:2473-83. 12. Perren TJ, et al. A phase 3 trial of bevacizumab in ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2484-96. 13. Aghajanian C, et al. OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol. 2012 Jun 10;30(17):2039-45. 14. Krishnansu S., et al. Improved Survival with Bevacizumab in Advanced Cervical Cancer. N Engl Med. 2014;370:734-43. 15. Seto T., et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44.

For further information: Roche Hong Kong Ltd. G.P.O. Box 11331, Hong Kong. Tel: 2723 2832 Fax: 2877 6557

PM-HK-0118-07-2017 Valid until 4/7/2019 or until change is required in accordance with the regulatory requirements, whichever comes first.

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