Current status of radiosensitizing agents for the management of rectal cancer

Critical Reviews in Oncogenesis

Volumn 17, Issue 4, 2012, Pages 345-359

  Illum, Henrik ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

5 FU; Bevacizumab; Cetuximab; Induction chemotherapy; Ironotecan; Oxaliplatin; PCR

Indexed keywords

BEVACIZUMAB; BIOLOGICAL MARKER; CAPECITABINE; CARBOPLATIN; CETUXIMAB; CISPLATIN; DNA TOPOISOMERASE; EPIDERMAL GROWTH FACTOR RECEPTOR; FLUOROURACIL; FOLINIC ACID; GIMERACIL PLUS OTERACIL POTASSIUM PLUS TEGAFUR; IRINOTECAN; OXALIPLATIN; RADIOSENSITIZING AGENT; THYMIDINE PHOSPHORYLASE; UFT;

ACNE; ADVANCED CANCER; ARTICLE; CANCER ADJUVANT THERAPY; CANCER PATIENT; CANCER STAGING; CHEMORADIOTHERAPY; COLORECTAL CANCER; CONTINUOUS INFUSION; DERMATITIS; DIARRHEA; DISEASE FREE SURVIVAL; DRUG EFFICACY; DRUG INTERMITTENT THERAPY; DRUG TOLERABILITY; GENE DOSAGE; HEAD AND NECK CANCER; HEALTH CARE QUALITY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LEUKOPENIA; LUNG NON SMALL CELL CANCER; OVERALL SURVIVAL; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROCTITIS; PROTEIN EXPRESSION; PROTEINURIA; RECTUM CANCER; STATISTICAL SIGNIFICANCE;

CHEMORADIOTHERAPY; DISEASE MANAGEMENT; HUMANS; NEOADJUVANT THERAPY; RADIATION-SENSITIZING AGENTS; RECTAL NEOPLASMS;

EID: 84870324294     PISSN: 08939675     EISSN: 21626448     Source Type: Journal    
DOI: 10.1615/CritRevOncog.v17.i4.40     Document Type: Article

References (108)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277-300.
2. Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart A. Revised tumor and node categorization for rectal cancer based on surveillance, epidemiology, and end results and rectal pooled analysis outcomes. J Clin Oncol. 2010;28(2):256-63.
3. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997;336(14):980-7.
4. Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373(9666):811-20.
5. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten, H. J. Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-46.
6. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group in Cancer. J Clin Oncol. 1998;16(1):301-8.
7. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000;18(16):2938-47.
8. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000;355(9209):1041-7.
9. Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109-16.
10. Twelves C, Wong A, Nowacki MP, Abt M, Burris H, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352(26):2696-704.
11. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet. 1995;345(8955):939-44.
12. Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs. 2000;18(4):299-313.
13. Pinedo HM, Peters GF. Fluorouracil: bio-chemistry and pharmacology. J Clin Oncol. 1988;6(10):1653-64.
14. Heidelberger C, Griesbach L, Cruz O, Schnitzer RJ, Grunberg E. Fluorinated pyrimidines. VI. Effects of 5-fluorouridine and 5-fluoro-2'-deoxyuridine on transplanted tumors. Proc Soc Exp Biol Med. 1958;97(2):470-5.
15. Lawrence TS, Davis MA, Loney TL. Fluoropyrimidine-mediated radiosensitization depends on cyclin E-dependent kinase activation. Cancer Res. 1996;56(14):3203-6.
16. Axelson MD, Davis MA, Ethier SP, Lawrence TS. HPV16-E7 expression causes fluorodeoxyuridinemediated radiosensitization in SW620 human colon cancer cells. Neoplasia. 1999;1(2):177-82.
17. Byfield JE, Calabro-Jones P, Klisak I, Kulhanian F. Pharmacologic requirements for obtaining sensitization of human tumor cells in vitro to combined 5-Fluorouracil or ftorafur and X rays. Int J Radiat Oncol Biol Phys. 1982;8(11):1923-33.
18. Shewach DS, Lawrence TS. Antimetabolite radio-sensitizers. J Clin Oncol. 2007;25(26):4043-50.
19. Hansen RM, Quebbeman E, Anderson T. 5-Fluorouracil by protracted venous infusion: a review of current progress. Oncology. 1989;46(4):245-50.
20. O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994;331(8):502-7.
21. Minsky BD, Cohen AM, Kemeny N, Enker WE, Kelsen DP, Reichman B, Saltz L, Sigurdson ER, Frankel J. Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol. 1992;10(1):79-84.
22. Bosset JF, Magnin V, Maingon P, Mantion G, Pelissier EP, Mercier M, Chaillard G, Horiot JC. Preoperative radiochemotherapy in rectal cancer: long-term results of a phase II trial. Int J Radiat Oncol Biol Phys. 2000;46(2):323-7.
23. Carau B, Orru P, Orru S, Dessi M, Nagliati M, Lay G, Maxia V, Casula G, Amichetti M. Neoadjuvant radiochemotherapy treatment in locally advanced rectal adenocarcinoma. Tumori. 2003;89(4 Suppl):7-8.
24. Chen ET, Mohiuddin M, Brodovsky H, Fishbein G, Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys. 1994;30(1):169-75.
25. Grann A, Minsky BD, Cohen AM, Saltz L, Guillem JG, Paty PB, Kelsen DP, Kemeny N, Ilson D, Bass-Loeb J. Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer. Dis Colon Rectum. 1997;40(5):515-22.
26. Grann A, Feng C, Wong D, Saltz L, Paty PP, Guillem JG, Cohen AM, Minsky BD. Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2001;49(4):987-95.
27. Kuchenmeister U, Kirchner R, Mellert J, Klautke G, Mucke R, Hopt UT, Fietkau R. First results of neoadjuvant simultaneious radiochemotherapy in advanced rectal carcinoma. Strahlenther Onkol. 2000;176(12):560-6.
28. Mehta VK, Poen J, Ford J, Edelstein PS, Vierra M, Bastidas AJ, Young H, Fisher G. Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 or T4 rectal cancer. Dis Colon Rectum. 2001;44(1):52-8.
29. Ngan SY, Burmeister BH, Fisher R, Rischin D, Schache DJ, Kneebone A, MacKay JR, Joseph D, Bell A, Goldstein D. Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a phase II trial for the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2001;50(4):883-7.
30. Nudelman IL, Fuko V, Geller A, Fenig E, Lelchuk S. Treatment of rectal cancer by chemoradiation followed by surgery: analysis and early clinical outcome in 66 patients. Isr Med Assoc J. 2005;7(6):377-80.
31. Rich TA, Skibber JM, Ajani JA, Buchholz DJ, Cleary KR, Dubrow RA, Levin B, Lynch PM, Meterissian SH, Roubein LD. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys. 1995;32(4):1025-9.
32. Tjandra JJ, Reading DM, McLachlan SA, Gunn IF, Green MD, McLaughlin SJ, Millar JL, Pedersen JS. Phase II clinical trial of preoperative combined chemoradiation for T3 and T4 resectable rectal cancer: preliminary results. Dis Colon Rectum. 2001;44(8):1113-22.
33. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-23.
34. Bosset JF, 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(24):5620-7.
35. Gerard JP, Conroy T, Bonnetain F, Bouche O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24(28):4620-5.
36. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731-40.
37. Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23(34):8688-96.
38. Janjan NA, Crane C, Feig BW, Cleary K, Dubrow R, Curley S, Vauthey JN, Lynch P, Ellis LM, Wolff R, Lenzi R, Abbruzzese J, Pazdur R, Hoff PM, Allen P, Brown T, Skibber J.Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol. 2001;24(2):107-12.
39. Janjan NA, Abbruzzese J, Pazdur R, Khoo VS, Cleary K, Dubrow R, Ajani J, Rich TA, Goswitz MS, Evetts PA, Allen PK, Lynch PM, Skibber JM. Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol. 1999;51(2):153-60.
40. Maas M, Nelemans PJ, Valentini V, Das P, Rodel C, Kuo LJ, Calvo FA, Garcia-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W Jr, Suarez J, Theodoropoulos G, Biondo S, Beets-Tan RG, Beets GL. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11(9):835-44.
41. Cassidy J, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzen F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008;26(12):2006-12.
42. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007;25(30):4779-86.
43. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465-71.
44. Shimma N, Umeda I, Arasaki M, Murasaki C, Masubuchi K, Kohchi Y, Miwa M, Ura M, Sawada N, Tahara H, Kuruma I, Horii I, Ishitsuka H. The design and synthesis of a new tumor-selective fluoropyrimidine carbamate, capecitabine. Bioorg Med Chem. 2000;8(7):1697-706.
45. Schuller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, Utoh M, Mori K, Weidekamm E, Reigner B. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45(4):291-7.
46. Sawada N, Ishikawa T, Fukase Y, Nishida M, Yoshikubo T, Ishitsuka H. Induction of thymidine phosphorylase activity and enhancement of capecitabine efficacy by taxol/taxotere in human cancer xenografts. Clin Cancer Res. 1998;4(4):1013-9.
47. Kim JS, Cho MJ, Song KS, Yoon WH. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2002;54(2):403-8.
48. Craven I, Crellin A, Cooper R, Melcher A, Byrne P, Sebag-Montefiore D. Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer. Br J Cancer. 2007;97(10):1333-7.
49. Das P, Lin EH, Bhatia S, Skibber JM, Rodriguez-Bigas MA, Feig BW, Chang GJ, Hoff PM, Eng C, Wolff RA, Delclos ME, Krishnan S, Janjan NA, Crane CH. Preoperative chemoradiotherapy with capecitabine versus protracted infusion 5-fluorouracil for rectal cancer: a matched-pair analysis. Int J Radiat Oncol Biol Phys. 2006;66(5):1378-83.
50. De Paoli A, Chiara S, Luppi G, Friso ML, Beretta GD, Del Prete S, Pasetto L, Santantonio M, Sarti E, Mantello G, Innocente R, Frustaci S, Corvo R, Rosso R. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol. 2006;17(2):246-51.
51. Desai SP, El-Rayes BF, Ben-Josef E, Greenson JK, Knol JA, Huang EH. A phase II study of preoperative capecitabine and radiation therapy in patients with rectal cancer. Am J Clin Oncol. 2007;30(4):340-5.
52. Dunst J, Debus J, Rudat V, Wulf J, Budach W, Hoelscher T, Reese T, Mose S, Roedel C, Zuehlke H, Hinke A. Neoadjuvant capecitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: mature results of a phase II trial. Strahlenther Onkol. 2008;184(9):450-6.
53. Elwanis MA, Maximous DW, Elsayed MI, Mikhail NN. Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial. World J Surg Oncol. 2009;7:52.
54. Kim DY, Jung KH, Kim TH, Kim DW, Chang HJ, Jeong JY, Kim YH, Son SH, Yun T, Hong CW, Sohn DK, Lim SB, Choi HS, Jeong SY, Park JG. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2007;67(2):378-84.
55. Krishnan S, Janjan NA, Skibber JM, Rodriguez-Bigas MA, Wolff RA, Das P, Delclos ME, Chang GJ, Hoff PM, Eng C, Brown TD, Crane CH, Feig BW, Morris J, Vadhan-Raj S, Hamilton SR, Lin EH. Phase II study of capecitabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66(3):762-71.
56. Velenik V, Anderluh F, Oblak I, Strojan P, Zakotnik B. Capecitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: prospective phase II trial. Croat Med J. 2006;47(5):693-700.
57. Kim JC, Kim TW, Kim JH, Yu CS, Kim HC, Chang HM, Ryu MH, Park JH, Ahn SD, Lee SW, Shin SS, Kim JS, Choi EK. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2005;63(2):346-53.
58. Hofheinz R, Wenz F, Post S, Matzdorff A, Laechelt S, Mueller L, Link H, Moehler M, Burkholder I, Hochhaus A. Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo-) adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): Safety results of a randomized, phase III trial. J Clin Oncol 27:15, 2009. (suppl; abstr 4014)
59. Hofheinz R, Wenz FK, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler MH, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Gencer D, Burkholder I, Hochhaus A. Capecitabine (Cape) versus 5-fluorouracil (5-FU)-based (neo)adjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC): Long-term results of a randomized, phase III trial. J Clin Oncol 29: 2011. (suppl; abstr 3504)
60. Roh Gay MS, O'Connell MJ. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. J Clin Oncol 29: 2011. (suppl; abstr 3503).
61. Porschen R, Arkenau HT, Kubicka S, Greil R, Seufferlein T, Freier W, Kretzschmar A, Graeven U, Grothey A, Hinke A, Schmiegel W, Schmoll HJ. Phase III study of capecitabine plus oxaliplatin compared with fluorouracil and leucovorin plus oxaliplatin in metastatic colorectal cancer: a final report of the AIO Colorectal Study Group. J Clin Oncol. 2007;25(27):4217-23.
62. Huerta S, Hrom J. Oxaliplatin as a radiosensitizing agent in rectal cancer. Anticancer Drugs. 2011;22(4):317-23.
63. Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. 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. 2011;29(20):2773-80.
64. Gerard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, Francois E, de La Roche G, Bouche O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahe MA, Becouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. 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. 2010;28(10):1638-44.
65. Chen AY, Choy H, Rothenberg ML. DNA topoisomerase I-targeting drugs as radiation sensitizers. Oncology. 1999;13(10 Suppl 5):39-46.
66. Slichenmyer WJ, Von Hoff DD. New natural products in cancer chemotherapy. J Clin Pharmacol. 1990;30(9):770-88.
67. Lamond JP, Wang M, Kinsella TJ, Boothman DA. Radiation lethality enhancement with 9-aminocamptothecin: comparison to other topoisomerase I inhibitors. Int J Radiat Oncol Biol Phys. 1996;36(2):369-76.
68. Amorino GP, Hercules SK, Mohr PJ, Pyo H, Choy H. Preclinical evaluation of the orally active camptothecin analog, RFS-2000 (9-nitro-20(S)-camptothecin) as a radiation enhancer. Int J Radiat Oncol Biol Phys. 2000;47(2):503-9.
69. Omura M, Torigoe S, Kubota N. SN-38, a metabolite of the camptothecin derivative CPT-11, potentiates the cytotoxic effect of radiation in human colon adenocarcinoma cells grown as spheroids. Radiother Oncol. 1997;43(2):197-201.
70. Tamura K, Takada M, Kawase I, Tada T, Kudoh S, Okishio K, Fukuoka M, Yamaoka N, Fujiwara Y, Yamakido M. Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts. Jpn J Cancer Res. 1997;88(2):218-23.
71. Seymour MT, Maughan TS, Ledermann JA, Topham C, James R, Gwyther SJ, Smith DB, Shepherd S, Maraveyas A, Ferry DR, Meade AM, Thompson L, Griffiths GO, Parmar MK, Stephens RJ. Different strategies of sequential and combination chemo-therapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet. 2007;370(9582):143-52.
72. Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D, Quinaux E, Couteau C, Buyse M, Ganem G, Landi B, Colin P, Louvet C, de Gramont A. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2004;22(2):229-37.
73. Colucci G, Gebbia V, Paoletti G, Giuliani F, Caruso M, Gebbia N, Carteni G, Agostara B, Pezzella G, Manzione L, Borsellino N, Misino A, Romito S, Durini E, Cordio S, Di Seri M, Lopez M, Maiello E, Montemurro S, Cramarossa A, Lorusso V, Di Bisceglie M, Chiarenza M, Valerio MR, Guida T, Leonardi V, Pisconti S, Rosati G, Carrozza F, Nettis G, Valdesi M, Filippelli G, Fortunato S, Mancarella S, Brunetti C. Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia Meridionale. J Clin Oncol. 2005;23(22):4866-75.
74. Illum H. Irinotecan and radiosensitization in rectal cancer. Anticancer Drugs. 2011;22(4):324-9.
75. 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(4):650-5.
76. Horisberger K, Erben P, Muessle B, Woernle C, Stroebel P, Kaehler G, Wenz F, Hochhaus A, Post S, Willeke F, Hofheinz RD. Topoisomerase I expression correlates to response to neoadjuvant irinotecan-based chemoradiation in rectal cancer. Anticancer Drugs. 2009;20(6):519-24.
77. Diaz-Gonzalez JA, Calvo FA, Cortes J, de La Mata D, Gomez-Espi M, Lozano MA, Lozano E, Serrano J, Herranz R. Preoperative chemoradiation with oral tegafur within a multidisciplinary therapeutic approach in patients with T3-4 rectal cancer. Int J Radiat Oncol Biol Phys. 2005;61(5):1378-84.
78. Uzcudun AE, Batlle JF, Velasco JC, Sanchez Santos ME, Carpeno Jde C, Grande AG, Juberias AM, Pineiro EH, Olivar LM, Garcia AG. Efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma when combined with oral tegafur-uracil modulated with leucovorin: results from a phase II study. Dis Colon Rectum. 2002;45(10):1349-58.
79. Calvo FA, Gomez-Espi M, Diaz-Gonzalez JA, Cantalapiedra R, Marcos P, Alvarado A, Garcia Alfonso P, Herranz R, Alvarez E. Pathologic downstaging of T3-4Nx rectal cancer after chemoradiation: 5-fluorouracil vs. Tegafur. Int J Radiat Oncol Biol Phys. 2001;51(5):1264-70.
80. Hoff PM, Janjan N, Saad ED, Skibber J, Crane C, Lassere Y, Cleary KR, Benner S, 80. Randolph J, Abbruzzese JL, Pazdur R. Phase I study of preoperative oral uracil and tegafur plus leucovorin and radiation therapy in rectal cancer. J Clin Oncol. 2000;18(20):3529-34.
81. Bystrom P, Frodin JE, Berglund A, Wilking N, Glimelius B. Phase I study of UFT plus leucovorin with radiotherapy in patients with inextirpable non-rectal gastrointestinal cancer. Radiother Oncol. 2004;70(2):171-5.
82. Fernandez-Martos C, Aparicio J, Bosch C, Torregrosa M, Campos JM, Garcera S, Vicent JM, Maestu I, Climent MA, Mengual JL, Tormo A, Hernandez A, Estevan R, Richart JM, Viciano V, Uribe N, Campos J, Puchades R, Arlandis F, Almenar D. Preoperative uracil, tegafur, and concomitant radiotherapy in operable rectal cancer: a phase II multicenter study with 3 years' follow-Up. J Clin Oncol. 2004;22(15):3016-22.
83. Hong YS, Lee JL, Park JH, Kim JH, Yoon SN, Lim SB, Yu CS, Kim MJ, Jang SJ, Lee JS, Kim JC, Kim TW. hase I study of preoperative chemoradiation with s-1 and oxaliplatin in patients with locally advanced resectable rectal cancer. Int J Radiat Oncol Biol Phys. 2011;79(3):684-9.
84. Shin SJ, Kim NK, Keum KC, Kim HG, Im JS, Choi HJ, Baik SH, Choen JH, Jeung HC, Rha SY, Roh JK, Chung HC, Ahn JB. Phase II study of preoperative chemoradiotherapy (CRT) with irinotecan plus S-1 in locally advanced rectal cancer. Radiother Oncol. 2010;95(3):303-7.
85. Sato T, Ozawa H, Hatate K, Onosato W, Naito M, Nakamura T, Ihara A, Koizumi W, Hayakawa K, Okayasu I, Yamashita K, Watanabe M. A Phase II trial of neoadjuvant preoperative chemoradiotherapy with S-1 plus irinotecan and radiation in patients with locally advanced rectal cancer: clinical feasibility and response rate. Int J Radiat Oncol Biol Phys. 2011;79(3):677-83.
86. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350(23):2335-42.
87. Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res. 2004;64(11):3731-6.
88. Winkler F, Kozin SV, Tong RT, Chae SS, Booth MF, Garkavtsev I, Xu L, Hicklin DJ, Fukumura D, di Tomaso E, Munn LL, Jain RK. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell. 2004;6(6):553-63.
89. Wildiers H, Guetens G, De Boeck G, Verbeken E, Landuyt B, Landuyt W, de Bruijn EA, van Oosterom AT. Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11. Br J Cancer. 2003;88(12):1979-86.
90. Willett CG, Boucher Y, Duda DG, di Tomaso E, Munn LL, Tong RT, Kozin SV, Petit L, Jain RK, Chung DC, Sahani DV, Kalva SP, Cohen KS, Scadden DT, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Shellito PC, Mino-Kenudson M, Lauwers GY. 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(31):8136-9.
91. Willett CG, Boucher Y, di Tomaso E, Duda DG, Munn LL, Tong RT, Chung DC, Sahani DV, Kalva SP, Kozin SV, Mino M, Cohen KS, Scadden DT, Hartford AC, Fischman AJ, Clark JW, Ryan DP, Zhu AX, Blaszkowsky LS, Chen HX, Shellito PC, Lauwers GY, Jain RK. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat Med. 2004;10(2):145-7.
92. Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Long TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RK. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009;27(18):3020-6.
93. Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, Thomas J, Ludwig KA, Mantyh CR, Ashton J, Yu D, Hurwitz HI. Bevacizumab, oxaliplatin, and capecitabine with radiation therapy in rectal cancer: Phase I trial results. Int J Radiat Oncol Biol Phys. 2007;68(2):472-8.
94. Crane CH, Eng C, Feig BW, Das P, Skibber JM, Chang GJ, Wolff RA, Krishnan S, Hamilton S, Janjan NA, Maru DM, Ellis LM, Rodriguez-Bigas MA. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2010;76(3):824-30.
95. Koukourakis MI, Giatromanolaki A, Tsoutsou P, Lyratzopoulos N, Pitiakoudis M, Kouklakis G, Chloropoulou PA, Manolas K, Sivridis E. Bevacizumab, capecitabine, amifostine, and preoperative hypofractionated accelerated radiotherapy (Hypo-Arc) for rectal cancer: a Phase II study. Int J Radiat Oncol Biol Phys. 2011;80(2):492-8.
96. Spigel DR, Bendell JC, McCleod M, Shipley DL, Arrowsmith E, Barnes EK, Infante JR, Burris HA, Greco FA, Hainsworth JD. Phase II Study of Bevacizumab and Chemoradiation in the Preoperative or Adjuvant Treatment of Patients With Stage II/ III Rectal Cancer. Clin Colorectal Cancer. 2012 Mar;11(1):45-52.
97. Velenik V, Ocvirk J, Music M, Bracko M, Anderluh F, Oblak I, Edhemovic I, Brecelj E, Kropivnik M, Omejc M. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study. Radiat Oncol. 2011;6:105.
98. Van Cutsem E, Kohne CH, Lang I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. 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.
99. Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354(6):567-78.
100. Hofheinz RD, Horisberger K, Woernle C, Wenz F, Kraus-Tiefenbacher U, Kahler G, Dinter D, Grobholz R, Heeger S, Post S, Hochhaus A, Willeke F. 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(5):1384-90.
101. Machiels JP, Sempoux C, Scalliet P, Coche JC, Humblet Y, Van Cutsem E, Kerger J, Canon JL, Peeters M, Aydin S, Laurent S, Kartheuser A, Coster B, Roels S, Daisne JF, Honhon B, Duck L, Kirkove C, Bonny MA, Haustermans K. Phase I/II study of preoperative cetuximab, capecitabine, and external beam radiotherapy in patients with rectal cancer. Ann Oncol. 2007;18(4):738-44.
102. Rodel C, Arnold D, Hipp M, Liersch T, Dellas K, Iesalnieks I, Hermann RM, Lordick F, Hinke A, Hohenberger W, Sauer R. Phase I-II trial of cetuximab, capecitabine, oxaliplatin, and radiotherapy as preoperative treatment in rectal cancer. Int J Radiat Oncol Biol Phys. 2008;70(4):1081-6.
103. Bertolini F, Chiara S, Bengala C, Antognoni P, Dealis C, Zironi S, Malavasi N, Scolaro T, Depenni R, Jovic G, Sonaglio C, Rossi A, Luppi G, Conte PF. 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(2):466-72.
104. Velenik V, Ocvirk J, Oblak I, Anderluh F. A phase II study of cetuximab, capecitabine and radiotherapy in neoadjuvant treatment of patients with locally advanced resectable rectal cancer. Eur J Surg Oncol. 2010;36(3):244-50.
105. Kim SY, Hong YS, Kim DY, Kim TW, Kim JH, Im SA, Lee KS, Yun T, Jeong SY, Choi HS, Lim SB, Chang HJ, Jung KH. Preoperative chemoradiation with Cetuximab, Irinotecan, and Capecitabine in patients with locally advanced resectable rectal cancer: a multicenter phase II study. Int J Radiat Oncol Biol Phys. 2011;81(3):677-83.
106. Horisberger K, Treschl A, Mai S, Barreto-Miranda M, Kienle P, Strobel P, Erben P, Woernle C, Dinter D, Kahler G, Hochhaus A, Post S, Willeke F, Wenz F, Hofheinz RD. 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;74(5):1487-93.
107. Bengala C, Bettelli S, Bertolini F, Salvi S, Chiara S, Sonaglio C, Losi L, Bigiani N, Sartori G, Dealis C, Malavasi N, D'Amico R, Luppi G, Gatteschi B, Maiorana A, Conte PF. 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(3):469-74.
108. Erben P, Strobel P, Horisberger K, Popa J, Bohn B, Hanfstein B, Kahler G, Kienle P, Post S, Wenz F, Hochhaus A, Hofheinz RD. KRAS and BRAF mutations and PTEN expression do not predict efficacy of Cetuximab-based chemoradiotherapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):1032-8.