臨床外科67巻7号

2012年07月発行

特集 分子標的薬の有害事象とその対策

分子標的薬による消化器毒性とその対策

著者： 大木暁¹ 山口研成¹

所属機関： ¹埼玉県立がんセンター消化器内科

ページ範囲：P.882 - P.888

【ポイント】

◆分子標的薬の投与開始前に，全身状態評価，併用禁忌薬，薬剤相互作用などの情報を最新の添付文書で確認する必要がある．

◆多種多様な毒性プロファイルがあるため，慎重なモニタリングを行うことが肝要である．

◆有害事象のマネージメントが治療効果を維持するために不可欠である．

参考文献

1）Roila F, Herrstedt J, Aapro M, et al：Guideline update for MASCC and ESMO in the prevention of chemotherapy-and radiotherapy-induced nausea and vomiting：results of the Perugia consensus conference. Ann Oncol 21 Suppl 5：v232-243, 2010

2）Basch E, Prestrud AA, Hesketh PJ, et al：Antiemetics：American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 29：4189-4198, 2011

3）日本癌治療学会（編）：制吐薬適正使用ガイドライン2010年5月．第1版．金原出版，2010，pp1-85

4）Deininger MW, O'Brien SG, Ford JM, et al：Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol 21：1637-1647, 2003

5）Loriot Y, Perlemuter G, Malka D, et al：Drug insight：gastrointestinal and hepatic adverse effects of molecular-targeted agents in cancer therapy. Nat Clin Pract Oncol 5：268-278, 2008

6）Crown JP, Burris HA 3rd, Boyle F, et al：Pooled analysis of diarrhea events in patients with cancer treated with lapatinib. Breast Cancer Res Treat 112：317-325, 2008

7）Cohen SJ, Engstrom PF, Lewis NL, et al：Phase Ⅰ study of capecitabine and oxaliplatin in combination with the proteasome inhibitor bortezomib in patients with advanced solid tumors. Am J Clin Oncol 31：1-5, 2008

8）Benson AB 3rd, Ajani JA, Catalano RB, et al：Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22：2918-2926, 2004

9）Thomas SK, Fossella FV, Liu D, et al：Asian ethnicity as a predictor of response in patients with non-small-cell lung cancer treated with gefitinib on an expanded access program. Clin Lung Cancer 7：326-331, 2006

10）Strumberg D, Awada A, Hirte H, et al：Pooled safety analysis of BAY 43-9006（sorafenib）monotherapy in patients with advanced solid tumours：is rash associated with treatment outcome? Eur J Cancer 42：548-556, 2006

11）Keefe DM, Schubert MM, Elting LS, et al：Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 109：820-831, 2007

12）Epstein JB, Elad S, Eliav E, et al：Orofacial pain in cancer：part Ⅱ--clinical perspectives and management. J Dent Res 86：506-518, 2007

13）Gorsky M, Epstein J, Raviv A, et al：Topical minocycline for managing symptoms of recurrent aphthous stomatitis. Spec Care Dentist 28：27-31, 2008

14）Baldwin C, Weekes CE：Dietary advice with or without oral nutritional supplements for disease-related malnutrition in adults. Cochrane Database Syst Rev 9：CD002008, 2011

15）Hapani S, Chu D, Wu S：Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab：a meta-analysis. Lancet Oncol 10：559-568, 2009

16）Kozloff M, Yood MU, Berlin J, et al：Clinical outcomes associated with bevacizumab-containing treatment of metastatic colorectal cancer：the BRiTE observational cohort study. Oncologist 14：862-870, 2009

17）Kwitkowski VE, Prowell TM, Ibrahim A, et al：FDA approval summary：temsirolimus as treatment for advanced renal cell carcinoma. Oncologist 15：428-435, 2010

18）Frieling T, Heise J, Wassilew SW：Multiple colon ulcerations, perforation and death during treatment of malignant melanoma with sorafenib. Dtsch Med Wochenschr 134：e1-2, 1464-1466, 2009

19）Saif MW, Elfiky A, Salem RR：Gastrointestinal perforation due to bevacizumab in colorectal cancer. Ann Surg Oncol 14：1860-1869, 2007

20）Hang XF, Xu WS, Wang JX, et al：Risk of high-grade bleeding in patients with cancer treated with bevacizumab：a meta-analysis of randomized controlled trials. Eur J Clin Pharmacol 67：613-623, 2011

21）Llovet JM, Ricci S, Mazzaferro V, et al：Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359：378-390, 2008

22）Kikuchi S, Muroi K, Takahashi S, et al：Severe hepatitis and complete molecular response caused by imatinib mesylate：possible association of its serum concentration with clinical outcomes. Leuk Lymphoma 45：2349-2351, 2004

23）James C, Trouette H, Marit G, et al：Histological features of acute hepatitis after imatinib mesylate treatment. Leukemia 17：978-979, 2003

24）Ridruejo E, Cacchione R, Villamil AG, et al：Imatinib-induced fatal acute liver failure. World J Gastroenterol 13：6608-6111, 2007

25）Guilhot F：Indications for imatinib mesylate therapy and clinical management. Oncologist 9：271-281, 2004

26）Ohyashiki K, Kuriyama Y, Nakajima A, et al：Imatinib mesylate-induced hepato-toxicity in chronic myeloid leukemia demonstrated focal necrosis resembling acute viral hepatitis. Leukemia 16：2160-2161, 2002

27）Dhalluin-Venier V, Besson C, Dimet S, et al：Imatinib mesylate-induced acute hepatitis with autoimmune features. Eur J Gastroenterol Hepatol 18：1235-1237, 2006

28）Delgoffe GM, Powell JD：mTOR：taking cues from the immune microenvironment. Immunology 127：459-465, 2009

29）Nencioni A, Schwarzenberg K, Brauer KM, et al：Proteasome inhibitor bortezomib modulates TLR4-induced dendritic cell activation. Blood 108：551-558, 2006

30）日本肝臓学会：免疫抑制・化学療法により発症するB型肝炎対策ガイドライン．改訂版．（http://www.jsh.or.jp/medical/documents/HBV_Guideline_correct.pdf：2011年9月26日）

31）急性膵炎診療ガイドライン2010改訂出版委員会，日本腹部救急医学会，日本肝胆膵外科学会，日本膵臓学会，日本医学放射線学会，厚生労働科学研究費補助金（編）：急性膵炎診療ガイドライン2010第3版．金原出版，2009，pp1-176