Perioperative (Radio-)Chemotherapie des lokal fortgeschrittenen Rektumkarzinoms

详细信息    查看全文

• 作者：Prof. Dr. R.-D. Hofheinz (1)
  
  1. TagesTherapieZentrum (TTZ) am Interdisziplin盲ren Tumorzentrum Mannheim (ITM) ; Universit盲tsmedizin Mannheim ; Ruprecht-Karls-Universit盲t Heidelberg ; Theodor-Kutzer Ufer 1鈥? ; 68167 ; Mannheim ; Deutschland
  
• 关键词：Bevacizumab ; Capecitabin ; Cetuximab ; Oxaliplatin ; Panitumumab ; Bevacizumab ; Capecitabine ; Cetuximab ; Oxaliplatin ; Panitumumab
• 刊名：Der Onkologe
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：21
• 期：2
• 页码：117-128
• 全文大小：717 KB
• 参考文献：1. Aschele C, Cionini L, Lonardi S et al (2011) Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized Phase III trial. J Clin Oncol 29(20):2773鈥?780 CrossRef
  2. Bengala C, Bettelli S, Bertolini F et al (2009) Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer. Ann Oncol 20(3):469鈥?74 CrossRef
  3. Blaszkowsky LS, Ryan DP, Szymonifka J et al (2014) Phase I/II study of neoadjuvant bevacizumab, erlotinib and 5-fluorouracil with concurrent external beam radiation therapy in locally advanced rectal cancer. Ann Oncol 25(1):121鈥?26 CrossRef
  4. Bonnetain F, Bosset JF, Gerard JP et al (2012) What is the clinical benefit of preoperative chemoradiotherapy with 5FU/leucovorin for T3鈥? rectal cancer in a pooled analysis of EORTC 22921 and FFCD 9203 trials: surrogacy in question? Eur J Cancer 48(12):1781鈥?790 CrossRef
  5. Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114鈥?123 CrossRef
  6. Bosset JF, Calais G, Mineur L et al (2014) Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol 15:184鈥?90 CrossRef
  7. Breugom AJ, Broek CBM van den, Gijn W van et al (2013) The value of adjuvant chemotherapy in rectal cancer patients after preoperative radiotherapy or chemoradiation followed by TME-surgery: the PROCTOR/SCRIPT study. European Cancer Congress (ESMO/ECCO). Abstract 1
  8. Collette L, Bosset JF, Dulk M den et al (2007) Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol 25:4339鈥?340 CrossRef
  9. Crane C, Crane CH, Eng C et al (2010) Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 76(3):824鈥?30 CrossRef
  10. Czito BG, Bendell JC, Willett CG et al (2007) Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. Int J Radiat Oncol Biol Phys 68(2):472鈥?78 CrossRef
  11. Debucquoy A, Haustermans K, Daemen A et al (2009) Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer. J Clin Oncol 27(17):2751鈥?757 CrossRef
  12. Dellas K, H枚hler T, Reese T et al (2013) Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer. Radiat Oncol 8(1):90 (Epub ahead of print) CrossRef
  13. Dewdeney A, Capdevila J, Glimelius B et al (2011) EXPERT-C: a randomized phase II European multicenter trial of neoadjuvant chemotherapy (capecitabine/oxaliplatin) and chemoradiation (CRT) with or without cetuximab followed by total mesorectal excision (TME) in patients with MRI-defined high-risk. J Clin Oncol 291 (suppl; abstr 3513)
  14. Di Petrillo T, Pricolo V, Lagares-Garcia J et al (2009) Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation in clinical stage II-III rectal cancer J Clin Oncol 27:15s (suppl; abstr 4105)
  15. Erben P, Str枚bel P, Horisberger K et al (2011) KRAS & BRAF mutations and PTEN expression do not predict efficacy of cetuximab-based chemoradiotherapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 81(4):1032鈥?038 CrossRef
  16. Gerard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620鈥?625 CrossRef
  17. Gerard JP, Azria D, Gourgou-Bourgade S et al (2010) Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol 28:1638鈥?644 CrossRef
  18. G茅rard JP, Azria D, Gourgou-Bourgade S et al (2012) Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol 30(36):4558鈥?565 CrossRef
  19. Helbling D, Bodoky G, Gautschi O et al (2013) Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07. Ann Oncol 24:718鈥?25 CrossRef
  20. Hofheinz RD, Wenz F, Post S et al (2012) Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 13:579鈥?88 CrossRef
  21. Horisberger K, Treschl A, Mai S et al (2009) Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patients with locally advanced rectal cancer: results of a Phase II MARGIT trial. Int J Radiat Oncol Biol Phys 74(5):1487鈥?493 CrossRef
  22. Hong YS, Nam BH, Kim KP et al (2014) Adjuvant chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) for rectal cancer patients whose postoperative yp stage 2 or 3 after preoperative chemoradiotherapy: updated results of 3-year disease-free survival from a randomized phase II study (The ADORE). J Clin Oncol 32:5s (suppl; abstr 3502) CrossRef
  23. Marijnen CA (2008) Preoperative chemoradiotherapy regimen with capecitabine and bevacizumab in locally advanced rectal cancer: a feasibility study of the Dutch Coloretcal Cancer Group (DCCG). J Clin Oncol 26 (suppl; abstr 15040)
  24. Nogue M, Salud A, Vicente P et al (2009) Addition of bevacizumab to induction plus concomitant capecitabine-oxaliplatin (XELOX) chemoradiotherapy (CRT) in MRI poor prognosis locally advanced rectal cancer: Avacross study. J Clin Oncol 18S:193S (4100)
  25. O鈥機onnell MJ, Colangelo LH, Beart RW et al (2014) Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and BowelProject Trial R-04. J Clin Oncol 32:1927鈥?934 CrossRef
  26. P氓hlman L, Glimelius B (1990) Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Ann Surg 211:187鈥?95 CrossRef
  27. Petersen SH, Harling H, Kirkeby LT et al (2012) Postoperative adjuvant chemotherapy in rectal cancer operated for cure. (Review). Cochrane Database Syst Rev 3:CD004078
  28. Resch G, Vries A de, 脰fner D et al (2010) Preoperative treatment with capecitabine (C), bevacizumab (B), and radiotherapy (RT) for primary locally advanced rectal cancer (LARC): a two-stage phase II clinical trial. ASCO GI Cancer Symposium Abstract No. 496
  29. R枚del C, Sauer R (2007) Integration of novel agents into combined-modality treatment for rectal cancer patients. Strahlenther Onkol 183:227鈥?35 CrossRef
  30. R枚del C, Liersch T, Becker H et al (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13(7):679鈥?87 CrossRef
  31. R枚del C, Liersch T, Fietkau R et al (2014) Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: Results of the German CAO/ARO/AIO-04 randomized phase III trial. J Clin Oncol 32:5s (suppl; abstr 3500) CrossRef
  32. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731鈥?740 CrossRef
  33. Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30(16):1926鈥?933 CrossRef
  34. Schmoll HJ, Haustermans K, Price T et al (2014) Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. J Clin Oncol 32:5s (suppl; abstr 3501) CrossRef
  35. Sclafani F, Gonzalez D, Cunningham D et al (2013) TP53 status may predict benefit from cetuximab in high-risk, locally advanced rectal cancer: results of the EXPERT-C trial. European Cancer Congress ECC (ESMO/ECCO) 2013 late breaking abstr
  36. Velenik V, Ocvirk J, Oblak I, Anderluh F (2010) A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer. Eur J Surg Oncol 36(3):244鈥?50 CrossRef
  37. Willett CG, Boucher Y, Tomaso E di et al (2004) Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 10(2):145鈥?47 CrossRef
  38. Willett CG, Duda DG, Tomaso E di et al (2009) Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 27(18):3020鈥?026 CrossRef
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1433-0415

文摘

Background For patients with locally advanced rectal cancer (LARC) perioperative radiochemotherapy (RChT) has been recommended in German guidelines since the 1990s as a standard therapy. Neoadjuvant 5-fluorouracil (5-FU) based RChT was introduced 10 years ago as the standard of care instead of adjuvant RChT. The aim of the current overview is to discuss studies investigating the substitution of 5-FU by oral fluoropyrimidines, the relevance of adjuvant chemotherapy as well as the use of oxaliplatin and monoclonal antibodies in the perioperative treatment. Results Two studies demonstrated that capecitabine was non-inferior to intravenous 5-FU. Oxaliplatin has been investigated in the perioperative treatment in six large randomized trials and two of these trials have achieved the primary endpoint of prolonging disease-free survival (DFS): the Korean ADORE trial led to an improvement in DFS in high-risk patients receiving oxaliplatin in addition to 5-FU as postoperative therapy, while in the German CAO/ARO/AIO-04 study oxaliplatin was added to both neoadjuvant and adjuvant treatment also resulting in improved DFS. In contrast, the other four trials exhibited no benefits of perioperative oxaliplatin. Monoclonal antibodies have not been investigated in phase III trials in patients with LARC and should not be administered outside clinical trials. Conclusion Capecitabin can replace 5-FU in the perioperative treatment of LARC. Data regarding the use of oxaliplatin are not congruent. The use of oxaliplatin only in conjunction with neoadjuvant RChT cannot be recommended, while data of the CAO/ARO/AIO-04 trial indicate that the preoperative and postoperative use of additional oxaliplatin may be regarded as a new treatment option. Consideration should be given to the additional use of oxaliplatin in high-risk patients in the postoperative treatment according to the data from the ADORE trial.