Radiation, chemotherapy and biological therapy in the curative treatment of locally advanced rectal cancer

Colorectal Disease

Volumn 12, Issue SUPPL. 2, 2010, Pages 2-24

  Gollins, S ^a  

^a GLAN CLWYD HOSPITAL   (United Kingdom)

Author keywords

Biological therapy; Chemotherapy; Radiotherapy; Rectal cancer

Indexed keywords

BEVACIZUMAB; CAPECITABINE; CETUXIMAB; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; IRINOTECAN; METHOTREXATE; OXALIPLATIN; SEMUSTINE; TEGAFUR; URACIL; VINCRISTINE; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; RADIOSENSITIZING AGENT;

ADD ON THERAPY; ADJUVANT THERAPY; ADVANCED CANCER; BIOLOGICAL THERAPY; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER STAGING; CANCER SURGERY; CANCER SURVIVAL; CHRONIC DIARRHEA; CLINICAL EFFECTIVENESS; CLINICAL TRIAL; COLON CANCER; COLORECTAL CANCER; CONSERVATIVE TREATMENT; DIARRHEA; FATIGUE; FECES INCONTINENCE; HEAD AND NECK CANCER; HEALTH CARE QUALITY; HUMAN; INTERMETHOD COMPARISON; INTESTINAL DYSMOTILITY; MINIMALLY INVASIVE SURGERY; MORBIDITY; MULTIMODALITY CANCER THERAPY; MULTIPLE CYCLE TREATMENT; NUCLEAR MAGNETIC RESONANCE IMAGING; PARAMETER; PATIENT COMPLIANCE; PELVIS FRACTURE; POSTOPERATIVE COMPLICATION; PREOPERATIVE RADIOTHERAPY; PRIORITY JOURNAL; QUALITY OF LIFE; RADIATION DOSE FRACTIONATION; RECOMMENDED DRUG DOSE; RECTUM CANCER; RECTUM RESECTION; RECTUM SURGERY; REVIEW; SECOND CANCER; SEPSIS; SEXUAL DYSFUNCTION; SMALL INTESTINE OBSTRUCTION; STOMATITIS; SURGICAL TECHNIQUE; SYSTEMATIC REVIEW; THERAPY EFFECT; TRANSRECTAL ULTRASONOGRAPHY; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE; URINE INCONTINENCE; ABDOMINAL SURGERY; NEOPLASM RECURRENCE, LOCAL; PATHOLOGY; RECTAL NEOPLASMS;

ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; BIOLOGICAL THERAPY; COMBINED MODALITY THERAPY; DIGESTIVE SYSTEM SURGICAL PROCEDURES; HUMANS; NEOADJUVANT THERAPY; NEOPLASM RECURRENCE, LOCAL; NEOPLASM STAGING; RADIATION-SENSITIZING AGENTS; RECTAL NEOPLASMS;

EID: 77954719685     PISSN: 14628910     EISSN: 14631318     Source Type: Journal    
DOI: 10.1111/j.1463-1318.2010.02320.x     Document Type: Review

References (165)

1. Quirke P, Dixon MF, Durdey P, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 1986, 328:996-9.
2. Wibe A, Moller B, Norstein J, Carlsen E, Wiig JN, Heald RJ, Langmark F, Myrvold HE, Soreide O. A national strategic change in treatment policy for rectal cancer-implementation of total mesorectal excision as routine treatment in Norway. A national audit. Dis Colon Rectum 2002, 45:857-66.
3. Nagtegaal ID, Marijnen CA, Kranenbarg EK, van de Velde CJH, van Krieken JHJM. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimetre but two millimetres is the limit. Am J Surg Pathol 2002, 26:350-7.
4. Hall NR, Finan PJ, al-Jaberi T, Tsang CS, Brown SR, Dixon MF, Quirke P. Circumferential resection margin involvement after mesorectal excision of rectal cancer with curative intent. Predictor of survival but not local recurrence? Dis Colon Rectum 1998, 41:979-83.
5. Mawdsley S, Glynne-Jones R, Grainger J. Can histopathologic assessment of circumferential resection margin after preoperative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for 3-year disease-free survival? Int J Radiat Oncol Biol Phys 2005, 63:745-52.
6. Birbeck KF, Macklin CP, Tiffin NJ. Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery. Ann Surg 2002, 235:449-57.
7. Marijnen CAM, Nagtegaal ID, Kapiteijn E, Klein Kranenbarg E, Noordijk EM, van Krieken JHJM, van de Velde CJH. Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys 2003, 55:1311-20.
8. Nagtegaal ID, Quirke P. What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 2008, 26:303-12.
9. Quirke P, Steele R, Monson J. Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from the MRC CR07 and NCIC-CTG C016 randomised clinical trial. Lancet 2009, 373:821-8.
10. Cawthorn SJ, Parums DV, Gibbs NM, A'Hern RP, Caffarey SM, Broughton CI, Marks CG. Extent of mesorectal spread and involvement of lateral resection margins as prognostic factors after surgery for rectal cancer. Lancet 1990, 335:1055-9.
11. Wang C, Zhou ZG, Wang Z, Li L, Zheng YC, Zhao GP, Chen DY, Liu WP. Mesorectal spread and micrometastasis of rectal cancer studied with large slice technique and tissue microarray. J Surg Oncol 2005, 91:167-72.
12. Moriya Y, Hojo K, Sawada T, Koyama Y. Significance of lateral node dissection for advanced rectal carcinoma at or below the peritoneal reflection. Dis Colon Rectum 1989, 32:307-15.
13. Nagtegaal ID, Gosens MJEM. Combinations of tumour and treatment parameters are more discriminative for prognosis than the present TNM system in rectal cancer. J Clin Oncol 2007, 25:1647-50.
14. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001, 358:1291-304.
15. Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 2000, 284:1008-15.
16. Munro AJ, Bentley AHM. Adjuvant radiotherapy in operable rectal cancer: a systematic review. Semin Colon Rectal Surg 2002, 13:31-42.
17. Wong RKS, Tandan V, De Silva S, Figueredo A. Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev 2007, http://dx.doi.org/10.1002/14651858.CD002102.pub2, issue 2. Art. No.: CD002102. doi:
18. Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. Cancer 1995, 75:2269-75.
19. Improved survival with pre-operative radiotherapy in respectable rectal cancer. N Eng J Med 1997, 336:980-7.
20. Peeters KCMJ, Marijnen CAM, Nagtegaal ID. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg 2007, 246:693-701.
21. Sebag-Montefiore D, Stephens RJ, Steele R. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCI CCTG C016): a multicentre, randomised trial? Lancet 2009, 373:811-20.
22. Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol 2005, 23:5644-50.
23. Glimelius B. Rectal cancer irradiation. Long course, short course or something else? Acta Oncol 2006, 45:101301017.
24. Guillem JG. As in fly fishing, " matching the hatch" should govern the management of locally advanced rectal cancer. Ann Surg 2007, 246:702-4.
25. Kapiteijn E, Marijnen CA, Nagtegaal ID. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Eng J Med 2001, 345:638-46.
26. MacFarlane JK, Ryall RDH, Heald RJ. Mesorectal excision for rectal cancer. Lancet 1993, 341:457-60.
27. Nagtegaal ID, van de Velde CJH, Marijnen CAM, van Krieken JHJM, Quirke P. Low rectal cancer: a call for change in approach in abdominoperineal resection. J Clin Oncol 2005, 23:9257-64.
28. Marijnen CAM, Nagtegaal ID, Kranenbarg EK, Hermans J, van de Velde CJH, Leer JWH, van Krieken JHJM. No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol 2001, 19:1976-84.
29. Bosset J-F, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Briffaux A, Collette L. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer: preliminary results - EORTC 22921. J Clin Oncol 2005, 23:5620-7.
30. Bosset J-F, Collette L, Calais G. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006, 355:1114-23.
31. Gerard J-P, Conroy T, Bonnetain F. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006, 24:4620-5.
32. den Dulk M, Collette L, van de Velde CJH, Marijnen CAM, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bossett J-F. Quality of surgery in T3-4 rectal cancer: involvement of circumferential resection margin not influenced by preoperative treatment. Results from EORTC trial 22921. Eur J Cancer 2007, 43:1821-8.
33. Collette L, Bossett J-F, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Pierart M, Calais G. Patients with curative resection of cT3-T4 rectal cancer after preoperative radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial from the European Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol 2007, 25:4379-86.
34. Sauer R, Becker H, Hohenberger W. Preoperative versus postoperative radiotherapy for rectal cancer. N Eng J Med 2004, 351:1731-40.
35. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ 2006, 333:779-82.
36. Smith NJ, Barbachano Y, Norman A, Swift RI, Abulafi AM, Brown G. Prognostic significance of magnetic resonance imaging-detected extramural vascular invasion in rectal cancer. Br J Surg 2007, 95:229-36.
37. Brown G, Davies S, Williams GT. Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging? Br J Cancer 2004, 91:23-9.
38. Kachnic LA, Hong TS, Ryan DP. Rectal cancer at the crossroads: the dilemma of clinically staged T3, N0, M0 disease. J Clin Oncol 2008, 26:350-1.
39. Gunderson LL, Sargent DJ, Tepper JE. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004, 22:1785-96.
40. Guillem JG, Diaz-Gonzalez JA, Minsky BD. cT3N0 rectal cancer: potential overtreatment with chemoradiotherapy is warranted. J Clin Oncol 2008, 26:368-73.
41. Bujko K, Nowacki MP, Nasierowska-Guttmejer A. Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiat Oncol 2004, 72:15-24.
42. Glimelius B, Gronberg H, Jarhult J, Wallgren A, Cavallin-Stahl E. A systematic overview of radiation therapy effects in rectal cancer. Acta Oncol 2003, 42:476-92.
43. Marijnen CAM, Kapiteijn E, van de Velde CJH, Martijn H, Steup WH, Wiggers T, Kranenbarg EK, Leer JWH. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002, 20:817-25.
44. Pahlman L. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Br J Surg 1993, 80:1333-6.
45. Birgisson H, Pahlman L, Gunnarsson U, Glimelius B. Late adverse effects of radiation for rectal cancer - a systematic overview. Acta Oncol 2007, 46:504-16.
46. Pollack J, Holm T, Cedermark B. Late adverse effects of short-course preoperative radiotherapy in rectal cancer. Br J Surg 2006, 93:1519-25.
47. Dahlberg M, Glimelius B, Graf W, Påhlman L. Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomised study. Dis Colon Rectum 1998, 41:543-9.
48. Peeters KCMJ, van de Velde CJ, Leer JWH, Martijn H, Junggeburt JMC, Kranenbarg EK, Steup WH, Wiggers T, Rutten HJ, Marijnen CAM. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients - a Dutch Colorectal Cancer Group Study. J Clin Oncol 2005, 23:6199-206.
49. Marijnen CAM, van de Velde CJH, Putter H. Impart of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicentre randomised trial. J Clin Oncol 2005, 23:1847-58.
50. Pachler J, Wille-Jørgensen P. Quality of life after rectal resection for cancer, with or without permanent colostomy. Cochrane Database Syst Rev 2004, http://dx.doi.org/10.1002/14651858.CD004323.pub3, Issue 3. Art. No.: CD004323. doi:
51. Pietrzak L, Bujko K, Nowacki MP. Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiat Oncol 2007, 84:217-25.
52. Brooks S, Glynne-Jones R, Novell R, Harrison M, Brown K, Makris A. Short course continuous, hyperfractionated, accelerated radiation therapy (CHART) as preoperative treatment for rectal cancer. Acta Oncol 2006, 45:1079-85.
53. Coucke PA, Notter M, Matter M, Fasolini F, Calmes J-M, Schlumpf R, Schwegler N, Stamm B, Phuoc DoH, Bouzourene H. Effect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): is it a matter of days? Acta Oncol 2006, 45:1086-93.
54. Rominger CJ, Gunderson LL, Gelber RD. Radiation therapy alone or in combination with chemotherapy in the treatment of residual or inoperable carcinoma of the rectum and rectosigmoid or pelvic recurrence following colorectal surgery. Radiation Therapy Oncology Group study (76-16). Am J Clin Oncol 1985, 8:118-27.
55. Overgaard M, Bertelsen K, Dalmark M. A randomised feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma. Acta Oncol 1993, 32:547-53.
56. Frykholm GJ, Pahlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 2001, 50:433-40.
57. Sebag-Montefiore D, Glynne-Jones R, Mortensen N, Bedi C, Wilson C, Geh I, McDonald A. Pooled analysis of outcome measures including the histopathological R0 resection rate after pre-operative chemoradiation for locally advanced rectal cancer. Colorectal Dis 2005, 7(Suppl. 1):7.
58. Glynne-Jones R, Anyamene N. Just how useful an endpoint is complete pathological response after neoadjuvant chemoradiation in rectal cancer? Int J Radiat Oncol Biol Phys 2006, 66:319-20.
59. Sanghera P, Wong DWY, McConkey CC, Geh JI, Hartley A. Chemoradiotherapy for rectal cancer: an updated analysis of factors affecting pathological response. Clin Oncol 2008, 20:176-83.
60. Rodel C, Martus P, Papadoupolos T. Prognostic significance of tumour regression after preoperative radiotherapy for rectal cancer. J Clin Oncol 2005, 23:8688-96.
61. Capirci C, Valentini V, Cionini L. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 2008, 72:99-107.
62. Glynne-Jones R, Mawdsley S, Novell JR. The clinical significance of circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language. Colorectal Dis. 2006, 8:800-7.
63. Sebag-Montefiore D, Hingorani M, Cooper R, Chesser P. Circumferential resection margin status predicts outcome after pre-operative chemoradiation for locally advanced rectal cancer. J Clin Oncol 2005, Proceedings of ASCO Gastrointestinal Cancers Symposium, abst 193
64. Kulkarni T, Gollins S, Maw A, Hobson P, Byrne R, Widdowson D. Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential margin status. Colorectal Dis 2008, 10:479-89.
65. Merkel S, Mansmann U, Siassi M, Papadopoulos T, Hohenberger W, Hermanek P. The prognostic inhomogeneity in pT3 rectal carcinomas. Int J Colorectal Dis 2001, 16:298-304.
66. Quirke P, Williams GT. Minimum Dataset for Colorectal Cancer Histopathology Reports 1998, Royal College of Pathologists, London
67. Sawada N, Ishikawa T, Sekiguchi K, Tanaka Y, Ishitsuka H. X-ray irradiation induces thymidine phosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res 1999, 5:2948-53.
68. Glynne-Jones R, Dunst J, Sebag-Montefiore D. The integration of oral capecitabine into chemoradiation regimens for locally advanced rectal cancer: how successful have we been? Ann Oncol 2006, 17:361-71.
69. Kim DY, Jung KH, Kim TH. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2007, 67:378-84.
70. De la Torre A, Garcia-Berrocal MI, Arias F. Preoperative chemoradiotherapy for rectal cancer: Randomized trial comparing oral uracil and tegafur and oral leucovorin vs. intravenous 5-Fluorouracil and leucovorin. Int J Radiat Oncol Biol Phys 2008, 70:102-10.
71. Eder JP, Wong JS, Chan V. Irinotecan and radiation in vitro and in vivo. Int J Oncol 1997, 11:1235-40.
72. Chen AY, Ocunieff P, Pommier Y, Mitchell JB. Mammalian DNA Topoisomerase I mediates the enhancement of radiation cytotoxicity by Camptothysin derivatives. Cancer Res 1997, 57:1529-36.
73. Falk SJ, Smith PJ. DNA damaging and cell cycle effects of the Topoisomerase I poison Camptothysin in irradiated human cells. Int J Radiat Biol 1992, 61:749-57.
74. Omura M, Torigoe S, Kubota N. SN38 a metabolite of camptothecin derivative CPT-11 potentiates the cytotoxic effects of radiation in human colon adenocarcinoma cells grown as spheroids. Radiother Oncol 1997, 43:197-208.
75. Mitchell EP, Anne P, Fry R. Combined mortality therapy of locally advanced or recurrent adenocarcinoma of the rectum: report of a phase I trial of chemotherapy with CPT-11, 5-FU and concomitant irradiation. J Clin Oncol 2001, 20:abstr-519.
76. Mehta VK, Cho C, Ford JM. Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer. Int J Radiat Oncol Biol Phys 2003, 55:132-7.
77. Klautke G, Feyerherd P, Ludwig K, Prall F, Foitzik T, Fietkau R. Intensified concurrent chemoradiotherapy with 5-fluorouracil and irinotecan as neoadjuvant treatment in patients with locally advanced rectal cancer. Br J Cancer 2005, 92:1215-20.
78. Navarro M, Dotor E, Rivera F, Sanchez-Rovira P, Garcia JL, Vega-Villegas ME, Cervantes A, Garcia JL, Gallen M, Aranda E. A phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-flourouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2006, 66:201-5.
79. Mohiuddin M, Winter K, Mitchell E, Hanna N, Yuen A, Nichols C, Shane R, Hayostek C, Willett C. Randomized phase II study of neoadjuvant combined-modality chemoradiation for distal rectal cancer: radiation Therapy Oncology Group Trial 0012. J Clin Oncol 2006, 24:650-5.
80. Glynne-Jones R, Falk S, Maughan TS, Meadows HM, Sebag-Montefiore D. A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group study. Br J Cancer 2007, 96:551-8.
81. Iles SM, Gollins SW, Susnerwala S, Haylock B, Myint S, Biswas A, Swindell R, Levine E. Irinotecan + 5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study. Br J Cancer 2008, 98:1210-6.
82. Hofheinz RD, von Gerstenberg-Helldorf B, Wenz F, Gnad U, Kraus-Tiefenbacher U, Muldner A, Hehlmann R, Post S, Hochhaus A, Willeke F. Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer. J Clin Oncol 2005, 23:1350-7.
83. Klautke G, Kuchenmeister U, Foitzik T, Ludwig K, Prall F, Klar E, Fietkau R. Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study. Br J Cancer 2006, 94:976-81.
84. Willeke F, Horisberger K, Kraus-Tiefenbacher U. A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Br J Cancer 2007, 96:912-7.
85. Klautke G, Kuchenmeister U, Foitzik T, Ludwig K, Semrau S, Prall F, Klar E, Fietkau R. Intensified irinotecan-based neoadjuvant chemotherapy in rectal cancer: Four consecutive designed studies to minimize acute toxicity and to optimize efficacy measured by complete pathological response. Radiat Oncol 2007, 85:379-84.
86. Gollins SW, Myint S, Susnerwala S. Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2). Br J Cancer 2009, 101:924-34.
87. Blackstock A, Tepper J, Hess S. Oxaliplatin: in vitro and in vivo evidence of its radiation sensitizing activity. Int J Radiat Oncol Biol Phys 2000, 46:92-4.
88. Cividalli A, Ceciarelli F, Livdi E, Altavista P, Cruciani G, Marchetti P, Danesi DT. Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule. Int J Radiat Oncol Biol Phys 2002, 52:1092-109.
89. Alonso V, Salud A, Escudero P, Valencia J, Mira M, Ruiz de Lobera A, Lambea J, Grandez R, Tres A, Anton A. Preoperative chemoradiation with oxaliplatin and 5-fluorouracil in locally advanced rectal carcinoma. J Clin Oncol 2004, 14S:abst-3607. ASCO Annual Meeting Proceedings
90. Aschele C, Friso ML, Pucciarelli S. A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 2005, 16:1140-6.
91. Ryan DP, Niedzwiecki D, Hollis D, Mediema BE, Wadler S, Tepper JE, Goldberg RM, Mayer RJ. Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: cancer and Leukemia Group B 89901. J Clin Oncol 2006, 24:2557-62.
92. Rodel C, Grabenbauer GG, Papadopoulos T, Hohenberger W, Schmoll H-J, Sauer R. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol 2003, 16:3098-104.
93. Tucci E, Algeri R, Giulianotti PC, Pecci AP, Schiaroli G, Sbrana F, Perillo F. Preoperative capecitabine, oxaliplatin and high-dose pelvic conformal radiotherapy in locally advanced rectal cancer (LARC). J Clin Oncol 2004, 22:abst-3646.
94. Alonso V, Lambea J, Salud A, Valencia J, Mira M, Polo S, Escudero P, Sierra E, Monzon A. Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal carcinoma: a phase II trial. J Clin Oncol 2007, 25:abst-4044.
95. Machiels J-P, Duck L, Honhon B. Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study. Ann Oncol 2005, 16:1898-905.
96. Glynne-Jones R, Sebag-Montefiore D, Samuel L, Falk S, Maughan T, McDonald A. Socrates phase II study results: capecitabine (CAP) combined with oxaliplatin (OX) preoperative radiation (radiotherapy) in patients (pts) with locally advanced rectal cancer (LARC). J Clin Oncol 2005, 16S:abstr-3527. ASCO Annual Meeting Proceedings
97. Rutten H, Sebag-Montefiore D, Glynne-Jones R, Rullier E, Peeters M, Brown G, Van Cutsem E, Ricci S, Van de Velde CJ, Quirke P. Capecitabine, oxaliplatin, radiotherapy and excision (CORE) in patients with MRI-defined locally advanced rectal adenocarcinoma: results of an international multicenter phase II study. J Clin Oncol 2006, 18S:3528.
98. Rodel C, Liersch T, Hermann RM. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 2007, 25:110-7.
99. Aristu JJ, Arbea L, Rodriguez J, Hernandez-Lizoain JL, Sola JJ, Moreno M, Azcona JD, Diaz-Gonzalez JA, Garcia-Foncillas JM, Martinez-Monge R. Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2008, doi: 10.1016/j/ijrobp.2007.10.023
100. Koeberle D, Burkhard R, von Moos R. Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer. Br J Cancer 2008, 98:1204-9.
101. Fakih M, BullardDunn K, Yang GY. Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates in neoadjuvant treatment of rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2008, 72:650-7.
102. Rishe EM, Malamud S, Hu K. A novel 5-FU-oxaliplatin based chemoradiation schema for stage II and III rectal carcinoma: Updated results from a phase II study. 2008, Proc ASCO Gastrointestinal Cancers Symposium, abst 385
103. Aschele C, Pinto C, Cordio S, Rosati G, Tagliagambe A, Artale S, Rosetti P, Lonardi S, Boni L, Cionini L. Preoperative fluorouracil (FU)-based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)-01 randomised phase III trial. J Clin Oncol 2009, 27:18s.
104. Gerard J, Azria D, Gourgou-Bourgarde S, Martel-Laffay I, Hennequin C, Etienne P, Vendrely V, Conroy T, Francois E, Montoto-Grillot C. Randomised multicentre phase III trial comparing two neoadjuvant chemoradiotherapy (CT-RT) regimens (RT45-Cap versus RT50-Capox) in patients (pts) with locally advanced rectal cancer (LARC): results of the ACCORD 12/PRODIGE 2. J Clin Oncol 2009, 27:18s. (suppl; abstr LBA4007)
105. Heudel P, Romestaing P, Barbet N, Falandry C, You B, Glehen O, Freyer G. Capecitabine, irinotecan, oxaliplatin (CAPRINOX) and concomitant irradiation in advanced rectal cancer: the Lyon R-02-01 Phase I Trial. Clin Oncol 2008, 20:369-74.
106. Cunningham D, Humblet Y, Siena S. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Eng J Med 2004, 351:337-45.
107. Kawamato T, Sato JD, Le A, Polikoff J, Sato GH, Mendelsohn J. Growth stimulation of A431 cell by epidermal growth factor: identification of high-affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc Natl Acad Sci U S A 1983, 80:1337-41.
108. Saleh MN, Raisch KP, Stackhouse MA. Combined modality therapy of A431 human epidermoid cancer using anti-EGFR antibody C225 and radiation. Cancer Biother Radiopharm 1999, 14:451-63.
109. Bianco C, Bianco R, Tottora G. Antitumour activity of combined treatment of human cancer cells with ionising radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. Clin Cancer Res 2000, 6:4343-50.
110. Huang SM, Harari PM. Modulation of radiation response after epidermal growth factor blockade in squamous cell carcinomas: inhibition of damage repair, cell cycle kinetics and tumour angiogenesis. Clin Cancer Res 2000, 6:2166-74.
111. Bonner JA, Raisch KP, Trummell HQ. Enhanced apoptosis with combination C225/radiation treatment serves as the impetus for clinical investigation in head and neck cancers. J Clin Oncol 2000, 18(21S):47s-53s.
112. Czito BG, Bendell JC, Willett CG. Bevacizumab, Oxaliplatin, and Capecitabine With Radiation Therapy in Rectal Cancer: Phase I Trial Results. Int J Radiat Oncol Biol Phys 2007, 68:472-8.
113. Hofheinz R-D, Horisberger K, Woernle C. Phase I trial of cetuximab in combination with capecitabine, weekly irinotecan and radiotherapy as neoadjuvant therapy for rectal cancer. Int J Radiat Oncol Biol Phys 2006, 66:1384-90.
114. Hong YS, Kim DY, Lee KS, Lim SB, Choi HS, Jeong SY, Kim JH, Im SA, Kim TW, Jung KH. Phase II study of preoperative chemoradiation (CRT) with cetuximab, irinotecan and capecitabine in patients with locally advanced resectable rectal cancer. J Clin Oncol 2007, ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S abst 4045
115. Machiels J-P, Sempoux C, Scalliet P. Phase I/II study of preoperative cetuximab, capecitabine and external beam radiotherapy in patients with rectal cancer. Ann Oncol 2007, 18:738-44.
116. Rodel C, Arnold D, Hipp M. Phase I-II trial of cetuximab, capecitabine, oxaliplatin and radiotherapy as preoperative treatment in rectal cancer. Int J Radiat Oncol Biol Phys 2008, 70:1081-6.
117. Bertolini F, Chiara S, Bengala C. Neoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab and pelvic radiotherapy: a phase II study in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2009, 73:466-72.
118. Horisberger K, Treschl A, Mai S. 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 2009, http://dx.doi.org/10.1016/j.ijrobp.2008.10.014, published online doi:
119. Karapetis CS, Khambata-Ford S, Jonker DJ. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Eng J Med 2008, 359:1757-65.
120. Van Cutsem E, Kohne C-H, Hitre E. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Eng J Med 2009, 360:1408-17.
121. Bengala C, Bettelli S, Bertolini F. 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 2009, 20:469-74.
122. Debucquoy A, Haustermans K, Daemen A. Molecular response to cetuximab and efficacy of preoperative cetuximab-based chemoradiation in rectal cancer. J Clin Oncol 2009, http://dx.doi.org/10.1200/JCO.2008.18.5033, published online doi:
123. Valentini V, De Paoli A, Gambacorta MA. Infusional 5-Fluorouracil and ZD1839 (Gefitinib-Iressa) in combination with preoperative radiotherapy in patients with locally advanced rectal cancer: a phase I and II trial (1839IL/0092). Int J Radiat Oncol Biol Phys 2008, http://dx.doi.org/10.1016/j.ijrobp.2008.01.046, doi:
124. Hurwitz H, Fehrenbacher L, Novotny W. Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. N Eng J Med 2004, 350:2335-42.
125. Giantonio BJ, Catalano PJ, Meropol NJ, O'Dwyer PJ, Mitchell EP, Alberts SR, Schwartz MA, Benson AB. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007, 25:1539-44.
126. Bonner JA, Harari PM, Giralt J. Radiotherapy plus Cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 2006, 354:567-78.
127. Teicher BA, Holden SA, Ara G, Dupuis NP, Liu F, Yuan J, Ikebe M, Kakeji Y. Influence of an anti-angiogenic treatment on 9L gliosarcoma: oxygenation and response to cytotoxic therapy. Int J Cancer 1995, 61:732-7.
128. Citrin D, Menard C, Camphausen K. Combining radiotherapy and angiogenesis inhibitors: clinical trial design. Int J Radiat Oncol Biol Phys 2006, 64:15-25.
129. Willett CG, Boucher Y, di Tomaso E. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med 2004, 10:145-7.
130. Duda D, Jain RK, Willett CG. Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation with solid cancers. J Clin Oncol 2007, 26:4033-42.
131. Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F, Bergsland E, Ngai J, Holmgren E, Wang J, Hurwitz H. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst 2007, 99:1232-1239.
132. Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, Kabbinavar F, Novotny W, Sarkar S, Hurwitz H. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol 2005, 91:173-180.
133. Auer RA, Goodman KA, Saltz LB, Shia J, Temple LK, Guillem JG, Paty PB, Wong WD, Weiser MR. Rectal complications during bevacizumab treatment for metastatic rectal cancer are increased in the setting of prior irradiation. 2008, Proc ASCO Gastrointestinal Cancers Symposium, abst 345
134. Fisher B, Wolmark N, Rockette H. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: Results from NSABP Protocol R-01. J Natl Cancer Inst 1988, 80:21-9.
135. Cionini L, Cartei F, Manfredi B, Laliscia C, Sainato A, Valentini V, Lupatelli M, Pizzi GB, Osti M, Santoni R. Randomized study of preoperative chemoradiation (CTRT) in locally advanced rectal cancer: preliminary results. Int J Radiat Oncol Biol Phys 1999, 3(Suppl):abst-61.
136. Fietkau R, Barten M, Klautke G. Postoperative chemotherapy may not be necessary for patients with ypN0-category after neoadjuvant chemoradiotherapy of rectal cancer. Dis Colon Rectum 2006, 49:1284-92.
137. Chau I, Brown G, Cunningham D. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol 2006, 24:668-74.
138. Glynne-Jones R, Sebag-Montefiore D. Role of neoadjuvant chemotherapy in rectal cancer: interpretation of the EXPERT study. J Clin Oncol 2006, 24:4664-5.
139. Elsaid AA, El-shami K, Elkerm Y. Neoadjuvant FOLFOX4 followed by combined chemoradiotherapy in locally advanced mucinous adenocarcinoma of the rectum. 2008, Proc ASCO Gastrointestinal Cancers Symposium, abst 357
140. Cunningham D, Allum WH, Stenning SP. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Eng J Med 2006, 355:11-20.
141. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 2002, 359:1727-33.
142. Glynne-Jones R, Grainger J, Harrison M, Ostler P, Makris A. Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious? Br J Cancer 2006, 94:363-71.
143. Glynne-Jones R, Hoskin P. Neoadjuvant chemotherapy before chemoradiation: a flawed paradigm? J Clin Oncol 2007, 25:5281-6.
144. Posner MR, Hershock DM, Blajman CR. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Eng J Med 2007, 357:1705-15.
145. Glynne-Jones R, Meadows H, Wood W. Chemotherapy or no chemotherapy in clear margins after neoadjuvant chemoradiation in locally advanced rectal cancer: CHRONICLE a randomised phase III trial of control vs. capecitabine plus oxaliplatin. Clin Oncol 2007, 19:327-9.
146. Bujko K, Kepka L, Michalski W, Nowacki MP. Does rectal cancer shrinkage induced by preoperative radio(chemo)therapy increase the likelihood of anterior resection? A systematic review of randomised trials. Radiat Oncol 2006, 80:4-12.
147. Chmielik E, Bujko K, Nasierowska-Guttmejer A. Distal intramural spread of rectal cancer after preoperative radiotherapy: the results of a multicenter randomized clinical study. Int J Radiat Oncol Biol Phys 2006, 65:182-8.
148. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Silva e Sousa AH, Campos FG, Kiss DR, Joaquim G-R. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy. Long-term results. Ann Surg 2004, 240:711-8.
149. Habr-Gama A, Perez RO, Proscurshim I, Nunes Dos Santos RM, Kiss D, Gama-Rodriguez J, Cecconello I. Interval between surgery and neoadjuvant chemoradiation therapy for distal rectal cancer: does delayed surgery have an impact on outcome. Int J Radiat Oncol Biol Phys 2008, http://dx.doi.org/10.1016/j.ijrobp.2007.11.035, doi:
150. O'Neill BDP, Brown G, Heald RJ, Cunningham D, Tait DM. Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer. Lancet Oncol 2007, 8:625-33.
151. Guillem JG, Chessin DB, Shia J. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate endpoint. J Clin Oncol 2005, 23:3475-9.
152. Dzik-Jurasz A, Domenig C, George M, Wolber J, Padhani A, Brown G, Doran S. Diffusion MRI for prediction of response of rectal cancer to chemoradiation. Lancet 2002, 360:307-8.
153. Harisinghani MG, Barentsz J, Hahn PF, Deserno WM, Tabatabaei S, van de Kaa CH. Noninvasive detection of clinically occult lymph-node metastases in prostate cancer. N Engl J Med 2003, 348(25):2491-9.
154. Rasheed S, Guenther T, Talbot I, McDonald P, Northover J, Stirling J, Culver L, Glynne-Jones R, Padhani AR. USPIO - enhanced rectal cancer specimen MRI: how well does it correlate with node identification at histopathology? Colorectal Dis 2006, 8:721-721.
155. Di Fabio F, Pinto C, Fanti S, Ceccarelli C, Gentile AL, Rojas Llimpe FL, Nanni C, Mutri V, Cacciari N, Martoni A. Correlation between FDG-PET and pathologic response in patients with rectal cancer treated with neoadjuvant chemo-radiotherapy: first results of the Bologna Project. J Clin Oncol 2005, 23:abst-3623.
156. Calvo FA, Domper M, Matute R, Martínez-Lázaro R, Arranz JA, Desco M, Álvarez E, Carreras JL. 18F-FDG positron emission tomography staging and restaging in rectal cancer treated with preoperative chemoradiation. Int J Radiat Oncol Biol Phys 2004, 58:528-35.
157. Rebischung C, Gerard JP, Gayet J, Thomas G, Hamelin R, Laurent-Puig P. Prognostic value of p53 mutations in rectal carcinoma. Int J Cancer 2002, 100:131-5.
158. Reerink O, Karenbeld A, Plukker TT, Verschueren RC, Szabo BG, Sluiter WJ, Hospers GA, Mulder NH. Molecular prognostic factors in locally irresectable rectal cancer treated preoperatively by chemo-radiotherapy. Anticancer Res 2004, 24:1217-21.
159. Rodel C, Grabenbauer GG, Papadopoulos T, Bigalke M, Gunther K, Schick C, Peters A, Sauer R, Rodel F. Apoptosis as a cellular predictor for histopathologic response to neoadjuvant radiochemotherapy in patients with rectal cancer. Int J Radiat Oncol Biol Phys 2002, 52:294-303.
160. Watanabe T, Komuro Y, Kiyomatsu T, Kanazawa T, Kazama Y, Tanaka J, Yamamoto Y, Shirane M, Muto T, Nagawa H. Prediction of sensitivity of rectal cancer cells in response to preoperative radiotherapy by DNA microarray analysis of gene expression profiles. Cancer Res 2006, 66:333370-4.
161. Ghadimi BM, Grade M, Difilippantonio MJ. Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. J Clin Oncol 2005, 23:1826-38.
162. Kim J-S, Kim J-M, Li S, Yoon K-S, Song K-S, Kim K-H, Yeo S-G, Nam JS, Cho M-J. Epidermal growth factor receptor as a predictor of tumour downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy. Int J Radiat Oncol Biol Phys 2006, 66:195-200.
163. Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean J-P, Partensky C, Souquet JC, Adeleine P, Gerard J-P. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 Randomized Trial. J Clin Oncol 1999, 17:2396-402.
164. Willett CG, Duda D, di Tomaso E. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J Clin Oncol 2005, 23:8136-9.
165. Chau I, Cunningham D, Tait D, Brown G. Correspondence. J Clin Oncol 2006, 24:4665-6.