消化器がんに対する分子標的薬剤の開発
悪性腫瘍は本邦の死亡原因の第1位となっており，早期発見とともに治療開発による治療成績の改善は極めて重要である．特に消化器がんに対する治療開発はめざましく，新たな治療薬の登場が相次いでいる．細胞傷害性薬剤の併用による治療成績の向上の後，分子標的治療薬の上乗せ効果を期待した臨床試験が実施され，小分子化合物や抗体薬の有効性が示されてきた．さらに，近年ではマルチプレックス診断法によるプレスクリーニングに対する治療アプローチや免疫チェックポイント分子阻害薬による治療アプローチが重要である．一方で，複雑化・高額化するがん治療における専門医教育も本邦においては重要である．...
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| Published in | 日本内科学会雑誌 Vol. 105; no. 6; pp. 1051 - 1060 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Japanese |
| Published |
一般社団法人 日本内科学会
2016
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-5384 1883-2083 |
| DOI | 10.2169/naika.105.1051 |
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| Abstract | 悪性腫瘍は本邦の死亡原因の第1位となっており，早期発見とともに治療開発による治療成績の改善は極めて重要である．特に消化器がんに対する治療開発はめざましく，新たな治療薬の登場が相次いでいる．細胞傷害性薬剤の併用による治療成績の向上の後，分子標的治療薬の上乗せ効果を期待した臨床試験が実施され，小分子化合物や抗体薬の有効性が示されてきた．さらに，近年ではマルチプレックス診断法によるプレスクリーニングに対する治療アプローチや免疫チェックポイント分子阻害薬による治療アプローチが重要である．一方で，複雑化・高額化するがん治療における専門医教育も本邦においては重要である． |
|---|---|
| AbstractList | 悪性腫瘍は本邦の死亡原因の第1位となっており，早期発見とともに治療開発による治療成績の改善は極めて重要である．特に消化器がんに対する治療開発はめざましく，新たな治療薬の登場が相次いでいる．細胞傷害性薬剤の併用による治療成績の向上の後，分子標的治療薬の上乗せ効果を期待した臨床試験が実施され，小分子化合物や抗体薬の有効性が示されてきた．さらに，近年ではマルチプレックス診断法によるプレスクリーニングに対する治療アプローチや免疫チェックポイント分子阻害薬による治療アプローチが重要である．一方で，複雑化・高額化するがん治療における専門医教育も本邦においては重要である． |
| Author | 近藤, 俊輔 |
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| References | 23) Demetri GD, et al: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472-480, 2002. 9) Saltz LB, 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 26: 2013-2019, 2008. 28) Caplin ME, et al: Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371: 224-233, 2014. 3) Kang JH, et al: Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30: 1513-1518, 2012. 15) Mayer RJ, et al: Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 372: 1909-1919, 2015. 12) Bennouna J, et al: Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14: 29-37, 2013. 7) Wilke H, et al: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15: 1224-1235, 2014. 4) Ford HE, et al: Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 15: 78-86, 2014. 5) Bang YJ, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376: 687-697, 2010. 17) Valle J, et al: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362: 1273-1281, 2010. 16) Llovet JM, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390, 2008. 21) Conroy T, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364: 1817-1825, 2011. 2) Hironaka S, et al: Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 31: 4438-4444, 2013. 1) Koizumi W, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9: 215-221, 2008. 8) Hurwitz H, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342, 2004. 22) Von Hoff DD, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369: 1691-1703, 2013. 24) Demetri GD, et al: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368: 1329-1338, 2006. 6) Fuchs CS, et al: Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383: 31-39, 2014. 29) Yao JC, et al: Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364: 514-523, 2011. 20) Moore MJ, et al: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25: 1960-1966, 2007. 31) Le DT, et al: PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372: 2509-2520, 2015. 18) Okusaka T, et al: Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer 103: 469-474, 2010. 19) Burris HA 3rd, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403-2413, 1997. 27) Rinke A, et al: Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27: 4656-4663, 2009. 30) Raymond E, et al: Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364: 501-513, 2011. 11) Karapetis CS, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359: 1757-1765, 2008. 13) Peeters M, et al: Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28: 4706-4713, 2010. 26) Joensuu H, et al: One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 307: 1265-1272, 2012. 25) Demetri GD, et al: Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 295-302, 2013. 10) Van Cutsem E, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360: 1408-1417, 2009. 14) Grothey A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 303-312, 2013. |
| References_xml | – reference: 30) Raymond E, et al: Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364: 501-513, 2011. – reference: 4) Ford HE, et al: Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol 15: 78-86, 2014. – reference: 13) Peeters M, et al: Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28: 4706-4713, 2010. – reference: 22) Von Hoff DD, et al: Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369: 1691-1703, 2013. – reference: 19) Burris HA 3rd, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15: 2403-2413, 1997. – reference: 1) Koizumi W, et al: S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol 9: 215-221, 2008. – reference: 29) Yao JC, et al: Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364: 514-523, 2011. – reference: 17) Valle J, et al: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362: 1273-1281, 2010. – reference: 24) Demetri GD, et al: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368: 1329-1338, 2006. – reference: 2) Hironaka S, et al: Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol 31: 4438-4444, 2013. – reference: 5) Bang YJ, et al: Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet 376: 687-697, 2010. – reference: 11) Karapetis CS, et al: K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359: 1757-1765, 2008. – reference: 14) Grothey A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 303-312, 2013. – reference: 18) Okusaka T, et al: Gemcitabine alone or in combination with cisplatin in patients with biliary tract cancer: a comparative multicentre study in Japan. Br J Cancer 103: 469-474, 2010. – reference: 3) Kang JH, et al: Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol 30: 1513-1518, 2012. – reference: 12) Bennouna J, et al: Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14: 29-37, 2013. – reference: 21) Conroy T, et al: FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364: 1817-1825, 2011. – reference: 7) Wilke H, et al: Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol 15: 1224-1235, 2014. – reference: 10) Van Cutsem E, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360: 1408-1417, 2009. – reference: 16) Llovet JM, et al: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 359: 378-390, 2008. – reference: 20) Moore MJ, et al: Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 25: 1960-1966, 2007. – reference: 25) Demetri GD, et al: Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 295-302, 2013. – reference: 31) Le DT, et al: PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372: 2509-2520, 2015. – reference: 8) Hurwitz H, et al: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335-2342, 2004. – reference: 15) Mayer RJ, et al: Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med 372: 1909-1919, 2015. – reference: 26) Joensuu H, et al: One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 307: 1265-1272, 2012. – reference: 6) Fuchs CS, et al: Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383: 31-39, 2014. – reference: 9) Saltz LB, 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 26: 2013-2019, 2008. – reference: 27) Rinke A, et al: Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27: 4656-4663, 2009. – reference: 28) Caplin ME, et al: Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371: 224-233, 2014. – reference: 23) Demetri GD, et al: Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472-480, 2002. |
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| SubjectTerms | プレスクリーニング 免疫チェックポイント分子阻害薬 分子標的治療薬 消化器がん |
| Title | 消化器がんに対する分子標的薬剤の開発 |
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