Новые аспекты первой линии химиотерапии метастатического колоректального рака


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Аннотация

Колоректальный рак (КРР) устойчиво занимает 3-е место в мире в структуре заболеваемости и смертности. В последнее времяблагодаря прогрессу в химиотерапии и хирургическом лечении метастатического колоректального рака (мКРР) и использованию мультидисциплинарного подхода алгоритмы лечения больных изменились. В зависимости от клинической ситуации выделяют 4 группы больных мКРР: с исходно резектабельными метастазами, с потенциально операбельными метастазами, с неоперабельными метастазами с симптомным течением болезни или быстрым прогрессированием, которые могут перенести интенсивное лечение, а также группу больных с неоперабельными метастазами и выраженной сопутствующей патологией. Оказалось, что помимо мутаций в экзоне 2 гена KRAS есть еще целый ряд более редких мутаций (в экзонах 3 и 4 гена KRAS, а также мутации в гене NRAS), также определяющих резистентность к анти-EGFR-терапии. В исследовании PRIME 17% больных, отнесенных в соответствии со старым тестом в группу без мутации (KRAS wt), имеют эти редкие мутации. Выбор таргетного препарата в 1-й линии лечения больных мКРР с мутацией RAS ограничен только бевацизумабом, а у пациентов без мутации можно использовать как анти-EGFR моноклональные антитела, так и бевацизумаб. Наличие мутации BRAF является фактором негативного прогноза больных мКРР и коррелируется с уменьшением продолжительности жизни. Дальнейшие исследования в этой области помогут разрешить оставшиеся вопросы и оптимизировать лечебные подходы в отношении разных групп пациентов.

Об авторах

Елена Владимировна Артамонова

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина РАМН

д-р мед. наук, вед. науч. сотр.

Список литературы

  1. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
  2. Weber S.M, Jarnagin W.R, De Matteo R.P et al. Survival after resection of multiple hepatic colorectal metastases. Ann Surg Oncol 2000; 7: 643-50.
  3. Choti M.A, Sitzmann J.V, Tiburi M.F et al. Trends in long - term survival following liver resection for hepatic colorectal metastases. Ann Surg 2002; 235: 759-66.
  4. Tomlinson J.S, Jarnagin W.R, De Matteo R.P et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol 2007; 25: 4575-80.
  5. Adam R, Barroso C. Impact of the type and modalities of preoperative chemotherapy on the outcome of liver resection for colorectal metastases. J Clin Oncol 2011; 29. Abstr. 3519.
  6. Schmoll H.J, van Cutsem E, Stein A et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 2012; 23: 2479-516.
  7. Nordlinger B, Sorbye H, Glimelius B et al. Perioperative chemotherapy with FOLFOX-4 and surgery vs. surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet 2008; 371: 1007-16.
  8. Nordlinger B, Sorbye H, Glimelius B et al. Perioperative FOLFOX-4 chemotherapy and surgery vs. surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long - term results of a randomised, controlled, phase 3 trial. Lancet 2013; http://dx.doi.org/10.1016/S1470- 2045(13)70447-9
  9. Primrose J.N, Falk S, Finch-Jones M et al. A randomized clinical trial of chemotherapy compared to chemotherapy in combination with cetuximab in k-RAS wild - type patients with operable metastases from colorectal cancer: The new EPOC study. Proc ASCO 2013. Abstr. 3504.
  10. Saltz L.B, Clarke S, Diaz-Rubio E et al. Bevacizumab in combination with oxaliplatin - based chemotherapy as first - line therapy in metastatic colorectal cancer: a randomized phase III study. JCO 2008; 26: 2012-9.
  11. Cassidy J, Clarke S, Díaz-Rubio E et al. XELOX vs. FOLFOX-4 as first - line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cancer 2011; 105 (1): 58-64.
  12. Grothey A. A comparison of XELOX with FOLFOX-4 as first - line treatment for metastatic colorectal cancer. Nat Clin Pract Oncol 2009; 6 (1): 10-1.
  13. Tournigand C, André T, Achille E et al. FOLFIRI followed by FOLFOX-6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol 2004; 22 (2): 229-37.
  14. Jordan K, Kellner O, Kegel T et al. Phase II trial of capecitabine/irinotecan and capecitabine/oxaliplatin in advanced gastrointestinal cancers. Clin Colorectal Cancer 2004; 4 (1): 46-50.
  15. Kohne C.H, Greve De J, Hartmann J.T et al. Irinotecan combined with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first - line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol 2008; 19: 920-6.
  16. Fuchs C.S, Marshall J, Mitchell E et al. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluorpyrimidines in first - line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol 2007; 25: 4779-86.
  17. Goldberg R.M, Sargent D.J, Morton R.F et al. A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 2004; 22: 23-30.
  18. Falcone A, Ricci S, Brunetti I et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first - line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 2007; 25 (13): 1670-6.
  19. Saltz L.B, Clarke S, Diaz-Rubio E at al. Bevacizumab (Bev) in combination with XELOX or FOLFOX-4: efficacy results from XELOX- 1/NO16966, a randomized phase III trial in the first - line treatment of metastatic colorectal cancer (MCRC). GI Cancers Sympos 2007. Abstr. 238.
  20. Kabbinavar F, Hurwitz H.L, Fehrenbacher L et al. Phase II randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21: 60.
  21. Kabbinavar F.F, Schulz J, Mc Cleod M et al. Addition of bevacizumab to bolus fluorouracil and leucovorin in first - line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 2005; 23: 3697- 705.
  22. Hurwitz H, Fehrenbacher L, Novotny W et al. Bevacizumab plus irinotecan, fluorouracil and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350: 2335-42.
  23. Falcone A, Cremolini C, Masi G et al. FOLFOXIRI/bevacizumab (bev) vs. FOLFIRI/bev as first - line treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): Results of the phase III TRIBE trial by GONO group. J Clin Oncol 2013; 31. Abstr. 3505.
  24. Loupakis F, Schirripa M, Caparello C et al. Histopathologic evaluation of liver metastases from colorectal cancer in patients treated with FOLFO- XIRI plus bevacizumab. Brit J Cancer 2013; 108: 2549-56.
  25. Cunningham D, Lang I, Marcuello E et al. Bevacizumab plus capecitabin vs. capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open - label randomized phase III trial. Lancet Oncol 2013; 14: 1077-85.
  26. Saunders M.P, Lang I, Marcuello E et al. Efficacy and safety according to age subgroups in AVEX, a randomized phase III trial of bevacizumab in combination with capecitabine for the first - line treatment of elderly patients with metastatic colorectal cancer. J Clin Oncol 2013; 31. Abstr. 3521.
  27. Adams R.A, Meade A.M, Seymour M.T et al. Intermittent vs. continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first - line treatment of advanced colorectal cancer: results of the randomized phase 3 MRC COIN trial. Lancet Oncol 2011; 12 (7): 642-53.
  28. Maughan T.S, Adams R.A, Smith C.G et al. Addition of cetuximab to oxaliplatin - based first - line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 2011; 377 (9783): 2103-14.
  29. Tveit K, Guren T, Glimelius B et al. Randomized phase III study of 5-flurouracil/folinate/oxaliplatin given continuously or intermittently with or without cetuximab, as first - line therapy of metastatic colorectal cancer: the NORDIC VII study (NCT0014314), by the Nordic Colorectal Cancer Biomodulation Group. J Clin Oncol 2011; 29 (Suppl. 4). Abstr. 365.
  30. Zhou S.W, Huang Y.Y, Wei Y et al. No survival benefit from adding cetuximab or panitumumab to oxaliplatin - based chemotherapy in the first - line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta - analysis. Ed.: A.Goel. Baylor University Medical Center, USA. PLoS ONE 2012; 7 (11): e50925.
  31. http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
  32. Jen J, Powell S.M, Papadopoulos N et al. Molecular determinants of dysplasia in colorectal lesions. Cancer Res 1994; 54: 5523-6.
  33. Engeland van M, Roemen G.M, Brink M et al. K-ras mutations and RASSF1 a promoter methylation in colorectal cancer. Oncogene 2002; 21 (23): 3792-5.
  34. Custodio A, Feliu J. Prognostic and predictive biomarkers for epidermal growth factor receptor - targeted therapy in colorectal cancer: beyond KRAS mutations. Critic Rev Oncol Hematol 2013 (85): 45-81.
  35. Di Fiore F, Blanchard F, Charbonnier F et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. Br J Cancer 2007; 96: 1166-9.
  36. Lievre A, Bachet J.B, Boige V et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol 2008; 26: 374-9.
  37. Douillard J.Y, Siena S, Cassidy J. Randomized, phase III study of panitumumab (pmab) with FOLFOX-4 compared to FOLFOX-4 alone as first - line treatment (tx) for metastatic colorectal cancer (mCRC): the PRIME trial. Eur J Cancer 2009; 7 (Suppl. 3): 10LBA.
  38. Douillard J.Y, Oliner K.S, Siena S et al. Panitumumab FOLFOX-4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023-34.
  39. Rosen O, Yi J, Hurwitz H.I et al. Clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Ann Oncol 2008; 19 (Suppl. 6): 19. Abstr. 0-035.
  40. Hurwitz H.I, Yi J, Ince W et al. The clinical benefit of bevacizumab in metastatic colorectal cancer is independent of K-ras mutation status: analysis of phase III study of bevacizumab with chemotherapy in previously untreated metastatic colorectal cancer. Oncol 2009; 14 (1): 22-8.
  41. Heinemann V, von Weikersthal L.F, Deker T et al. Randomized comparison of FOLFIRI plus cetuximab vs. FOLFIRI plus bevacizumab as first - line treatment of KRAS wild - type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol 2013; 31 (Suppl.). Abstr. LBA3506.
  42. Heinemann V, Stintzing S, Jung A, Rossius L. Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: A randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first - line treatment for wild - type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. Eur J Cancer 2013; 49 (Suppl. 3). Abstr. LBA17.
  43. Schwartzberg L.S, Rivera F, Karthaus M et al. Analysis of KRAS/NRAS mutations in PEAK: A randomized phase II study of FOLFOX-6 plus panitumumab (pmab) or bevacizumab (bev) as first - line treatment (tx) for wild - type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC). J Clin Oncol 2013; 31 (Suppl.). Abstr. 3631.
  44. Oliner K.S, Douillard J-Y, Siena S et al. Analysis of KRAS/NRAS and BRAF mutations in the phase III PRIME study of panitumumab (pmab) plus FOLFOX vs. FOLFOX as first - line treatment (tx) for metastatic colorectal cancer (mCRC). J Clin Oncol 2013; 31 (Suppl.). Abstr. 3511.
  45. Tol J, Nagtegaal I.D, Punt C.J. BRAF mutation in metastatic colorectal cancer. N Engl J Med 2009; 361 (1): 98-9.
  46. Souglakos J, Philips J, Wang R et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br J Cancer 2009; 101 (3): 465-72.
  47. van Cutsem E, Kohne C.H, Laґng I et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first - line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 2011; 29 (15): 2011-9.
  48. Bokemeyer C, Bondarenko I, Hartmann J.T et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first - line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol 2011; 22 (7): 1535-46.
  49. Ince W.L, Jubb A.M, Holden S.N et al. Association of k - ras, b - raf, and p53 status with the treatment effect of bevacizumab. J Natl Cancer Inst 2005; 97 (13): 981-9.
  50. Richman S.D, Seymour M.T, Chambers P et al. KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan: results from the MRC FOCUS trial. J Clin Oncol 2009; 27 (35): 5931-7.

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