V．大腸癌化学療法の将来展望
大腸癌の化学療法は，近年の新規分子標的薬の導入により，目覚ましい進歩を遂げている．RASをはじめとした，がん関連遺伝子変異と化学療法の有効性に関する報告やBRAF変異例に対する新規治療開発により，治療方法も個別化されつつある．現在明らかになっている遺伝子変異と化学療法の有効性に関する情報や，新規抗癌剤を含めた今後の治療戦略と将来展望について最新の知見を交えて報告する．...
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| Published in | 日本大腸肛門病学会雑誌 Vol. 67; no. 10; pp. 906 - 918 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本大腸肛門病学会
2014
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0047-1801 1882-9619 |
| DOI | 10.3862/jcoloproctology.67.906 |
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| Abstract | 大腸癌の化学療法は，近年の新規分子標的薬の導入により，目覚ましい進歩を遂げている．RASをはじめとした，がん関連遺伝子変異と化学療法の有効性に関する報告やBRAF変異例に対する新規治療開発により，治療方法も個別化されつつある．現在明らかになっている遺伝子変異と化学療法の有効性に関する情報や，新規抗癌剤を含めた今後の治療戦略と将来展望について最新の知見を交えて報告する． |
|---|---|
| AbstractList | 大腸癌の化学療法は，近年の新規分子標的薬の導入により，目覚ましい進歩を遂げている．RASをはじめとした，がん関連遺伝子変異と化学療法の有効性に関する報告やBRAF変異例に対する新規治療開発により，治療方法も個別化されつつある．現在明らかになっている遺伝子変異と化学療法の有効性に関する情報や，新規抗癌剤を含めた今後の治療戦略と将来展望について最新の知見を交えて報告する． |
| Author | 土井, 綾子 土井, 俊彦 設楽, 紘平 |
| Author_xml | – sequence: 1 fullname: 土井, 綾子 organization: 国立がん研究センター東病院消化管内科 – sequence: 1 fullname: 設楽, 紘平 organization: 国立がん研究センター東病院先端医療科 – sequence: 1 fullname: 土井, 俊彦 organization: 国立がん研究センター東病院先端医療科 |
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| Copyright | 2014 日本大腸肛門病学会 |
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| References | 11) Phase I study of the selective BRAFV600 inhibitor encorafenib (LGX818) combined with cetuximab and with or without the α-specific PI3K inhibitor BYL719 in patients with advanced BRAF-mutant colorectal cancer. J Clin Oncol 2014;32 Suppl; LBA3514 22) Overman MJ, Kopetz S, Varadhachary G, et al: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest 26:794-799, 2008 24) Doi T, Ohtsu A, Yoshino T, et al: Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours. Br J Cancer 107:429-434, 2012 30) Yoshino T, Yamazaki K, Yoshida M, et al: A phase Ib study of irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) plus ramucirumab drug product in Japanese (JP) patients (pts) with metastatic colorectal carcinoma progressive during or following first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine [abstract]. J Clin Oncol 30:591, 2012 33) Wang T, Niu G, Kortylewski M, et al: Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 10:48-54, 2004 13) Sartore-Bianchi A, Martini M, Molinari F, et al: PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851-1857, 2009 31) Garcia-Carbonero R, Rivera F, Maurel J, et al: A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy in patients (pts) with metastatic colorectal cancer: CP12-0709 [abstract]. J Clin Oncol 30:533, 2012 9) Corcoran RB, Edi H, Turke AB, et al: EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancer to RAF inhibition with vemurafenib. Cancer Discov 2:227-235, 2012 15) Turner N, Grose R: Fibroblast growth factor signalling: from development to cancer. Nature reviews Cancer 10:116-129, 2010 20) Demetri GD, Reichardt P, Kang Y-K, 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. The Lancet 381:295-302, 2013 29) Spratlin JL, Cohen RB, Eadens M, et al: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28:780-787, 2010 12) Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). J Clin Oncol 2014;32 Suppl; LBA3515 26) Van Cutsem E, Tabernero J, Lakomy R, et al: Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499-3506, 2012 19) Grothey A, Cutsem EV, Sobrero A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. The Lancet 381:303-312, 2013 7) Corcoran RB, Falchook GS, Jeffrey R, et al: BRAF V600 mutant colorectal cancer (CRC) expansion cohort from the phase I/II clinical trial of BRAF inhibitor dabrafenib (GSK2118436) plus MEK inhibitor trametinib (GSK1120212) [abstract]. J Clin Oncol 30 Suppl; LBA3528, 2012 34) Langleben A, Jeffrey G, Sebastien J, et al: A dose-escalation phase I study of a first-in-class cancer stemness inhibitor in patients with advanced malignancies. [abstract]. J Clin Oncol 31 Suppl; LBA2542, 2013 10) Yang H, Higgins B, Kolinsky K, et al: Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer. Cancer Res 72:779-789, 2012 25) Yoshino T, Mizunuma N, Yamazaki K, et al: TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol 13:993-1001, 2012 6) Chapman PB, Hauschild A, Robert C, et al: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507-2516, 2011 21) Hong DS, Abbruzzese JL, Bogaard K, et al: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer 107:1383-1390, 2006 1) Van Cutsem E, Kohne CH, Hitre E, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408-1417, 2009 4) Schwartzberg LS, Rivera F, Karthaus M, et al: PEAK: A Randomized, Multicenter Phase II Study of Panitumumab plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer. J Clin Oncol 32:2240-2247, 2014 5) Van Loon K, Wigler D, Niedzwiecki D, et al: Comparison of dietary and lifestyle habits among stage III and metastatic colorectal cancer patients: findings from CALGB 89803 and CALGB 80405. Clin Colorectal Cancer 12:95-102, 2013 16) Bergers G, Song S, Meyer-Morse N, et al: Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. Journal of Clinical Investigation 111:1287-1295, 2003 28) Ellis LM, Hicklin DJ, et al: VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8:579-591, 2008 8) Prahallad A, Sun C, Huang S, et al: Unresponsiveness of colon cancer to BRAF (V600E) inhibition through feedback activation of EGFR. Nature 483:100-103, 2012 18) Strumberg D, Scheulen ME, Schultheis B, et al: Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. British journal of cancer 106:1722-1727, 2012 27) Yoshino T, Yamazaki K, Yamaguchi K, et al: A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer. Invest New Drugs 31:910-917, 2013 2) Douillard JY, Siena S, Cassidy J, et al: Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25:1346-1355, 2014 3) Heinemann V, von Weikersthal LF, Decker T, et al: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol S1470-2045:703330-703334, 2014 14) Fong G-H, Rossant J, Gertsenstein M, et al: Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66-70, 1995 17) Wilhelm SM, Dumas J, Adnane L, et al: Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. International journal of cancer Journal international du cancer 129:245-255, 2011 23) Overman MJ, Varadhachary G, Kopetz S, et al: Phase 1 study of TAS-102 administered once daily on a five-day-per-week schedule in patients with solid tumors. Invest New Drugs 26:445-454, 2008 32) Bromberg JF, Wrzeszczynska MH, Devgan G, et al: Stat3 as an oncogene. Cell 98:295-303, 1999 |
| References_xml | – reference: 15) Turner N, Grose R: Fibroblast growth factor signalling: from development to cancer. Nature reviews Cancer 10:116-129, 2010 – reference: 20) Demetri GD, Reichardt P, Kang Y-K, 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. The Lancet 381:295-302, 2013 – reference: 29) Spratlin JL, Cohen RB, Eadens M, et al: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28:780-787, 2010 – reference: 28) Ellis LM, Hicklin DJ, et al: VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer 8:579-591, 2008 – reference: 11) Phase I study of the selective BRAFV600 inhibitor encorafenib (LGX818) combined with cetuximab and with or without the α-specific PI3K inhibitor BYL719 in patients with advanced BRAF-mutant colorectal cancer. J Clin Oncol 2014;32 Suppl; LBA3514 – reference: 30) Yoshino T, Yamazaki K, Yoshida M, et al: A phase Ib study of irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) plus ramucirumab drug product in Japanese (JP) patients (pts) with metastatic colorectal carcinoma progressive during or following first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine [abstract]. J Clin Oncol 30:591, 2012 – reference: 19) Grothey A, Cutsem EV, Sobrero A, et al: Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. The Lancet 381:303-312, 2013 – reference: 33) Wang T, Niu G, Kortylewski M, et al: Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 10:48-54, 2004 – reference: 13) Sartore-Bianchi A, Martini M, Molinari F, et al: PIK3CA mutations in colorectal cancer are associated with clinical resistance to EGFR-targeted monoclonal antibodies. Cancer Res 69:1851-1857, 2009 – reference: 27) Yoshino T, Yamazaki K, Yamaguchi K, et al: A phase I study of intravenous aflibercept with FOLFIRI in Japanese patients with previously treated metastatic colorectal cancer. Invest New Drugs 31:910-917, 2013 – reference: 1) Van Cutsem E, Kohne CH, Hitre E, et al: Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 360:1408-1417, 2009 – reference: 4) Schwartzberg LS, Rivera F, Karthaus M, et al: PEAK: A Randomized, Multicenter Phase II Study of Panitumumab plus Modified Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) or Bevacizumab Plus mFOLFOX6 in Patients With Previously Untreated, Unresectable, Wild-Type KRAS Exon 2 Metastatic Colorectal Cancer. J Clin Oncol 32:2240-2247, 2014 – reference: 8) Prahallad A, Sun C, Huang S, et al: Unresponsiveness of colon cancer to BRAF (V600E) inhibition through feedback activation of EGFR. Nature 483:100-103, 2012 – reference: 14) Fong G-H, Rossant J, Gertsenstein M, et al: Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376:66-70, 1995 – reference: 17) Wilhelm SM, Dumas J, Adnane L, et al: Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. International journal of cancer Journal international du cancer 129:245-255, 2011 – reference: 18) Strumberg D, Scheulen ME, Schultheis B, et al: Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study. British journal of cancer 106:1722-1727, 2012 – reference: 26) Van Cutsem E, Tabernero J, Lakomy R, et al: Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499-3506, 2012 – reference: 10) Yang H, Higgins B, Kolinsky K, et al: Antitumor activity of BRAF inhibitor vemurafenib in preclinical models of BRAF-mutant colorectal cancer. Cancer Res 72:779-789, 2012 – reference: 22) Overman MJ, Kopetz S, Varadhachary G, et al: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest 26:794-799, 2008 – reference: 5) Van Loon K, Wigler D, Niedzwiecki D, et al: Comparison of dietary and lifestyle habits among stage III and metastatic colorectal cancer patients: findings from CALGB 89803 and CALGB 80405. Clin Colorectal Cancer 12:95-102, 2013 – reference: 32) Bromberg JF, Wrzeszczynska MH, Devgan G, et al: Stat3 as an oncogene. Cell 98:295-303, 1999 – reference: 34) Langleben A, Jeffrey G, Sebastien J, et al: A dose-escalation phase I study of a first-in-class cancer stemness inhibitor in patients with advanced malignancies. [abstract]. J Clin Oncol 31 Suppl; LBA2542, 2013 – reference: 9) Corcoran RB, Edi H, Turke AB, et al: EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancer to RAF inhibition with vemurafenib. Cancer Discov 2:227-235, 2012 – reference: 31) Garcia-Carbonero R, Rivera F, Maurel J, et al: A phase II, open-label study evaluating the safety and efficacy of ramucirumab combined with mFOLFOX-6 as first-line therapy in patients (pts) with metastatic colorectal cancer: CP12-0709 [abstract]. J Clin Oncol 30:533, 2012 – reference: 16) Bergers G, Song S, Meyer-Morse N, et al: Benefits of targeting both pericytes and endothelial cells in the tumor vasculature with kinase inhibitors. Journal of Clinical Investigation 111:1287-1295, 2003 – reference: 21) Hong DS, Abbruzzese JL, Bogaard K, et al: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer 107:1383-1390, 2006 – reference: 2) Douillard JY, Siena S, Cassidy J, et al: Final results from PRIME: randomized phase III study of panitumumab with FOLFOX4 for first-line treatment of metastatic colorectal cancer. Ann Oncol 25:1346-1355, 2014 – reference: 25) Yoshino T, Mizunuma N, Yamazaki K, et al: TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol 13:993-1001, 2012 – reference: 6) Chapman PB, Hauschild A, Robert C, et al: Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med 364:2507-2516, 2011 – reference: 12) Efficacy and tolerability in an open-label phase I/II study of MEK inhibitor trametinib (T), BRAF inhibitor dabrafenib (D), and anti-EGFR antibody panitumumab (P) in combination in patients (pts) with BRAF V600E mutated colorectal cancer (CRC). J Clin Oncol 2014;32 Suppl; LBA3515 – reference: 24) Doi T, Ohtsu A, Yoshino T, et al: Phase I study of TAS-102 treatment in Japanese patients with advanced solid tumours. Br J Cancer 107:429-434, 2012 – reference: 23) Overman MJ, Varadhachary G, Kopetz S, et al: Phase 1 study of TAS-102 administered once daily on a five-day-per-week schedule in patients with solid tumors. Invest New Drugs 26:445-454, 2008 – reference: 3) Heinemann V, von Weikersthal LF, Decker T, et al: FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomized, open-label, phase 3 trial. Lancet Oncol S1470-2045:703330-703334, 2014 – reference: 7) Corcoran RB, Falchook GS, Jeffrey R, et al: BRAF V600 mutant colorectal cancer (CRC) expansion cohort from the phase I/II clinical trial of BRAF inhibitor dabrafenib (GSK2118436) plus MEK inhibitor trametinib (GSK1120212) [abstract]. J Clin Oncol 30 Suppl; LBA3528, 2012 |
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