A phase II experience with neoadjuvant irinotecan (CPT-11), 5-fluorouracil (5-FU) and leucovorin (LV) for colorectal liver metastases

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• 作者：Oliver F Bathe (1) (2)
  Scott Ernst (3)
  Francis R Sutherland (1)
  Elijah Dixon (1)
  Charles Butts (4)
  David Bigam (5)
  David Holland (6)
  Geoffrey A Porter (7)
  Jennifer Koppel (1)
  Scot Dowden (2)
  
• 刊名：BMC Cancer
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：9
• 期：1
• 全文大小：329KB
• 参考文献：1. Andres A, Majno PE, Morel P, Rubbia-Brandt L, Giostra E, Gervaz P, / et al.: Improved Long-Term Outcome of Surgery for Advanced Colorectal Liver Metastases: Reasons and Implications for Management on the Basis of a Severity Score. / Ann Surg Oncol 2008, 15: 134鈥?3. CrossRef
  2. Shah SA, Bromberg R, Coates A, Rempel E, Simunovic M, Gallinger S: Survival after liver resection for metastatic colorectal carcinoma in a large population. / J Am Coll Surg 2007, 205: 676鈥?3. CrossRef
  3. Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH: Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. / Ann Surg 1999, 230: 309鈥?8. CrossRef
  4. Parks R, Gonen M, Kemeny N, Jarnagin W, D'Angelica M, DeMatteo R, / et al.: Adjuvant chemotherapy improves survival after resection of hepatic colorectal metastases: analysis of data from two continents. / J Am Coll Surg 2007, 204: 753鈥?1. CrossRef
  5. Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, / et al.: Effect of Surgical Margin Status on Survival and Site of Recurrence After Hepatic Resection for Colorectal Metastases. / Ann Surg 2005, 241: 715鈥?4. CrossRef
  6. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, / et al.: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. / N Engl J Med 2000, 343: 905鈥?4. CrossRef
  7. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, / et al.: Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. / Lancet 2000, 355: 1041鈥?. CrossRef
  8. de Gramont A, Tournigand C, Louvet C, Maindrault-Goebel F, Andre T: First-line therapy for advanced colorectal cancer. / Curr Oncol Rep 2005, 7: 167鈥?2. CrossRef
  9. Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, / et al.: OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer 鈥?a GERCOR study. / J Clin Oncol 2006, 24: 394鈥?00. CrossRef
  10. Bathe O, Dowden S, Sutherland F, Dixon E, Butts C, Bigam D, / et al.: Phase II study of neoadjuvant 5-FU + leucovorin + CPT-11 in patients with resectable liver metastases from colorectal adenocarcinoma. / BMC Cancer 2004, 4: 32. CrossRef
  11. Ng J, Urbanski S, Mangat N, Sutherland F, Dixon E, Dowden S, / et al.: Colorectal liver metastases contract centripedally with a response to chemotherapy: a histomorphologic study. / Cancer 2008, 112: 362鈥?1. CrossRef
  12. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, / et al.: FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. / J Clin Oncol 2004, 22: 229鈥?7. CrossRef
  13. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, / et al.: New guidelines to evaluate the response to treatment in solid tumors. / J Natl Cancer Inst 2000, 92: 205鈥?6. CrossRef
  14. Bismuth H, Adam R, Levi F, Farabos C, Waechter F, Castaing D, / et al.: Resection of nonresectable liver metastases from colorectal cancer after neoadjuvant chemotherapy. / Ann Surg 1996, 224: 509鈥?2. CrossRef
  15. Pozzo C, Basso M, Cassano A, Quirino M, Schinzari G, Trigila N, / et al.: Neoadjuvant treatment of unresectable liver disease with irinotecan and 5-fluorouracil plus folinic acid in colorectal cancer patients. / Ann Oncol 2004, 15: 933鈥?. CrossRef
  16. Barone C, Nuzzo G, Cassano A, Basso M, Schinzari G, Giuliante F, / et al.: Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases. / Br J Cancer 2007, 97: 1035鈥?. CrossRef
  17. Adam R, Avisar E, Ariche A, Giachetti S, Azoulay D, Castaing D, / et al.: Five-year survival following hepatic resection after neoadjuvant therapy for nonresectable colorectal. / Ann Surg Oncol 2001, 8: 347鈥?3. CrossRef
  18. Delaunoit T, Alberts SR, Sargent DJ, Green E, Goldberg RM, Krook J, / et al.: Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741. / Ann Oncol 2005, 16: 425鈥?. CrossRef
  19. Moehler M, Hoffmann T, Zanke C, Hohl H, Burg H, Ehscheid P, / et al.: Safety and efficacy of outpatient treatment with CPT-11 plus bolus folinic acid/5-fluorouracil as first-line chemotherapy for metastatic colorectal cancer. / Anticancer Drugs 2003, 14: 79鈥?5. CrossRef
  20. Taieb J, Artru P, Paye F, Louvet C, Perez N, Andre T, / et al.: Intensive systemic chemotherapy combined with surgery for metastatic colorectal cancer: results of a phase II study. / J Clin Oncol 2005, 23: 502鈥?. CrossRef
  21. Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, / et al.: Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. / J Clin Oncol 2006, 24: 4976鈥?2. CrossRef
  22. Tanaka K, Adam R, Shimada H, Azoulay D, Levi F, Bismuth H: Role of neoadjuvant chemotherapy in the treatment of multiple colorectal metastases to the liver. / Br J Surg 2003, 90: 963鈥?. CrossRef
  23. Allen PJ, Kemeny N, Jarnagin W, DeMatteo R, Blumgart L, Fong Y: Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. / J Gastrointest Surg 2003, 7: 109鈥?5. CrossRef
  24. Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, / et al.: Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. / Lancet 2008, 371: 1007鈥?016. CrossRef
  25. Wein A, Riedel C, Bruckl W, Merkel S, Ott R, Hanke B, / et al.: Neoadjuvant treatment with weekly high-dose 5-fluorouracil as 24-hour infusion, folinic acid and oxaliplatin in patients with primary resectable liver metastases of colorectal cancer. / Oncology 2003, 64: 131鈥?. CrossRef
  26. Adam R, Pascal G, Castaing D, Azoulay D, Delvart V, Paule B, / et al.: Tumor progression while on chemotherapy: a contraindication to liver resection for multiple colorectal metastases? / Ann Surg 2004, 240: 1052鈥?1. CrossRef
  27. Alberts SR, Horvath WL, Sternfeld WC, Goldberg RM, Mahoney MR, Dakhil SR, / et al.: Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. / J Clin Oncol 2005, 23: 9243鈥?. CrossRef
  28. Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, / et al.: Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. / Ann Surg 2006, 243: 1鈥?. CrossRef
  29. Vauthey JN, Pawlik TM, Ribero D, Wu TT, Zorzi D, Hoff PM, / et al.: Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. / J Clin Oncol 2006, 24: 2065鈥?2. CrossRef
  30. Kooby D, Fong Y, Suriawinata A, Gonen M, Allen P, Klimstra D, / et al.: Impact of steatosis on perioperative outcome following hepatic resection. / J Gastrointest Surg 2003, 7: 1034鈥?4. CrossRef
  31. Seddighzadeh A, Shetty R, Goldhaber SZ: Venous thromboembolism in patients with active cancer. / Thromb Haemost 2007, 98: 656鈥?1.
  32. Rothenberg ML, Meropol NJ, Poplin EA, Van Cutsem E, Wadler S: Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. / J Clin Oncol 2001, 19: 3801鈥?.
  33. Pan CX, Loehrer P, Seitz D, Helft P, Juliar B, Ansari R, / et al.: A phase II trial of irinotecan, 5-fluorouracil and leucovorin combined with celecoxib and glutamine as first-line therapy for advanced colorectal cancer. / Oncology 2005, 69: 63鈥?0. CrossRef
  34. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/9/156/prepub
  
• 作者单位：Oliver F Bathe (1) (2)
  Scott Ernst (3)
  Francis R Sutherland (1)
  Elijah Dixon (1)
  Charles Butts (4)
  David Bigam (5)
  David Holland (6)
  Geoffrey A Porter (7)
  Jennifer Koppel (1)
  Scot Dowden (2)
  
  1. Department of Surgery, University of Calgary, Calgary, Canada
  2. Department of Oncology, University of Calgary, Calgary, Canada
  3. Department of Oncology, London Regional Cancer Centre, London, Canada
  4. Department of Oncology, University of Alberta, Edmonton, Canada
  5. Department of Surgery, University of Alberta, Edmonton, Canada
  6. Department of Oncology, Lethbridge Cancer Centre, Lethbridge, Canada
  7. Department of Surgery, Dalhousie University, Halifax, Canada
  
• ISSN：1471-2407

文摘

Background Chemotherapy may improve survival in patients undergoing resection of colorectal liver metastases (CLM). Neoadjuvant chemotherapy may help identify patients with occult extrahepatic disease (averting unnecessary metastasectomy), and it provides in vivo chemosensitivity data. Methods A phase II trial was initiated in which patients with resectable CLM received CPT-11, 5-FU and LV for 12 weeks. Metastasectomy was performed unless extrahepatic disease appeared. Postoperatively, patients with stable or responsive disease received the same regimen for 12 weeks. Patients with progressive disease received either second-line chemotherapy or best supportive care. The primary endpoint was disease-free survival (DFS); secondary endpoints included overall survival (OS) and safety. Results 35 patients were accrued. During preoperative chemotherapy, 16 patients (46%) had grade 3/4 toxicities. Resection was not possible in 5 patients. One patient died of arrhythmia following surgery, and 1 patient had transient liver failure. During the postoperative treatment phase, 12 patients (55%) had grade 3/4 toxicities. Deep venous thrombosis (DVT) occurred in 11 patients (34%) at various times during treatment. Of those who underwent resection, median DFS was 23.0 mo. and median OS has not been reached. The overall survival from time of diagnosis of liver metastases was 51.6 mo for the entire cohort. Conclusion A short course of chemotherapy prior to hepatic metastasectomy may serve to select candidates best suited for resection and it may also direct postoperative systemic treatment. Given the significant incidence of DVT, alternative systemic neoadjuvant regimens should be investigated, particularly those that avoid the use of a central venous line. Trial Registration ClinicalTrials.gov NCT00168155.