Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer

Radiation Oncology

Volumn 8, Issue 1, 2013, Pages

  Dellas, Kathrin ^a,b   Höhler, Thomas ^c   Reese, Thomas ^d   Würschmidt, Florian ^e   Engel, Erik ^f   Rödel, Claus ^g   Wagner, Wolfgang ^h   Richter, Michael ⁱ   Arnold, Dirk ^j   Dunst, Jürgen ^b  

^a UNIVERSITY OF KIEL   (Germany)

^b UNIVERSITY OF LÜBECK   (Germany)

^c PROSPER HOSPITAL   (Germany)

^d MARTIN LUTHER UNIVERSITY HALLE WITTENBERG   (Germany)

^e Private Practice   (Germany)

^f Private Practice   (Germany)

^g GOETHE UNIVERSITY   (Germany)

^h Department of Radiooncology ^*  (Germany)

ⁱ Biomathematics and Statistics   (Germany)

^j TUMOR BIOLOGY CENTER   (Germany)

more..

Author keywords

Bevacizumab; Capecitabine; Oxaliplatin; Preoperative radiochemotherapy; Rectal cancer

Indexed keywords

BEVACIZUMAB; CAPECITABINE; OXALIPLATIN; ANTINEOPLASTIC AGENT; DEOXYCYTIDINE; FLUOROURACIL; MONOCLONAL ANTIBODY; PLATINUM COMPLEX;

ABDOMINAL PAIN; ABSCESS; ADULT; ADVANCED CANCER; AGED; ANUS FISTULA; ARTICLE; CANCER ADJUVANT THERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER DIAGNOSIS; CANCER LOCALIZATION; CANCER RADIOTHERAPY; CANCER SURGERY; CHEMORADIOTHERAPY; CONSTIPATION; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DISEASE SEVERITY; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG TOLERABILITY; FATIGUE; FEASIBILITY STUDY; FEMALE; HAND FOOT SYNDROME; HUMAN; HYPERTENSION; ILEUS; LEUKOPENIA; LYMPH NODE METASTASIS; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; PAIN; PARESTHESIA; PELVIS ABSCESS; PHASE 2 CLINICAL TRIAL; POSTOPERATIVE COMPLICATION; PREOPERATIVE TREATMENT; PROCTITIS; RADIATION DOSE; RECTUM CANCER; RECTUM RESECTION; SENSORY NEUROPATHY; SOMNOLENCE; THROMBOCYTOPENIA; TREATMENT PLANNING; WOUND COMPLICATION; ADJUVANT THERAPY; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; MIDDLE AGED; PATHOLOGY; PROCEDURES; RADIATION DOSE FRACTIONATION; RECTAL NEOPLASMS; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CHEMORADIOTHERAPY; DEOXYCYTIDINE; DOSE FRACTIONATION; FEMALE; FLUOROURACIL; HUMANS; MALE; MIDDLE AGED; NEOADJUVANT THERAPY; ORGANOPLATINUM COMPOUNDS; RECTAL NEOPLASMS;

EID: 84876158464     PISSN: None     EISSN: 1748717X     Source Type: Journal    
DOI: 10.1186/1748-717X-8-90     Document Type: Article

References (44)

1. Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol 2012, 13(6):579-588.
2. Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC. EORTC Radiotherapy Group Trial 22921, Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006, 355(11):1114-1123.
3. Gérard JP, Conroy T, Bonnetain F, Bouché 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):4620-4625.
4. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. German Rectal Cancer Study Group, Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004, 351(17):1731-1740.
5. Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C. 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 2012, 30(16):1926-1933.
6. Valentini V, van Stiphout RG, Lammering G, Gambacorta MA, Barba MC, Bebenek M, Bonnetain F, Bosset JF, Bujko K, Cionini L, Gerard JP, Rödel C, Sainato A, Sauer R, Minsky BD, Collette L, Lambin P. Nomograms for predicting local recurrence, distant metastases, and overall survival for patients with locally advanced rectal cancer on the basis of European randomized clinical trials. J Clin Oncol 2011, 29(23):3163-3172.
7. Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo LJ, Calvo FA, García-Aguilar J, Glynne-Jones R, Haustermans K, Mohiuddin M, Pucciarelli S, Small W, Suárez 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):835-844.
8. Smith N, Brown G. Preoperative staging of rectal cancer. Acta Oncol 2008, 47(1):20-31.
9. Rödel C, Martus P, Papadoupolos T, Füzesi 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):8688-8696.
10. Vecchio FM, Valentini V, Minsky BD, Padula GD, Venkatraman ES, Balducci M, Miccichè F, Ricci R, Morganti AG, Gambacorta MA, Maurizi F, Coco C. The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 2005, 62(3):752-760.
11. Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, Paty PB, Weiser MR, Klimstra D, Saltz L, Minsky BD, Wong WD. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005, 241(5):829-836.
12. Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O'Connell MJ, Begovic M, Allmer C, Colangelo L, Smalley SR, Haller DG, Martenson JA, Mayer RJ, Rich TA, Ajani JA, MacDonald JS, Willett CG, Goldberg RM. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004, 22(10):1785-1796.
13. García-Aguilar J, Hernandez De Anda E, Sirivongs P, Lee SH, Madoff RD, Rothenberger DA. A pathologic complete response to preoperative chemoradiation is associated with lower local recurrence and improved survival in rectal cancer patients treated by mesorectal excision. Dis Colon Rectum 2003, 46(3):298-304.
14. 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):107-112.
15. Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, on behalf of the German Rectal Cancer Study Group 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 2012, 13(7):679-687. on behalf of the German Rectal Cancer Study Group.
16. 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):2773-2780.
17. Roh MS, Yothers GA, O'Connell MJ, Beart RW, Pitot HC, Shields AF, Parda DS, Sharif S, Allegra CJ, Petrelli NJ, Landry JC, Ryan DP, Arora A, Evans TL, Soori GS, Chu L, Landes RV, Mohiuddin M, Lopa S, Wolmark N. The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. J Clin Oncol 2011, 29:suppl 15; abstr 3503.
18. Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn 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):1638-1644.
19. Ferrara N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist 2004, 9(Suppl 1):2-10.
20. Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol 2002, 20(21):4368-4380.
21. 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):145-147.
22. Ranpura V, Hapani S, Wu S. Treatment-related mortality with bevacizumab in cancer patients: a meta-analysis. JAMA 2011, 305(5):487-494.
23. Rödel 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):1081-1086.
24. Rödel C, Liersch T, Hermann RM, Arnold D, Reese T, Hipp M, Fürst A, Schwella N, Bieker M, Hellmich G, Ewald H, Haier J, Lordick F, Flentje M, Sülberg H, Hohenberger W, Sauer R. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 2007, 25(1):110-117.
25. Rödel C, Grabenbauer GG, Papadopoulos T, Hohenberger W, Schmoll HJ, Sauer R. Phase I/II Trial of Capecitabine, Oxaliplatin, and Radiation for Rectal Cancer. J Clin Oncol 2003, 16(21):3098-3104.
26. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997, 12(1):19-23.
27. 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.
28. Kennecke H, Berry S, Wong R, Zhou C, Tankel K, Easaw J, Rao S, Post J, Hay J. Pre-operative bevacizumab, capecitabine, oxaliplatin and radiation among patients with locally advanced or low rectal cancer: a phase II trial. Eur J Cancer 2012, 48(1):37-45.
29. Dipetrillo T, Pricolo V, Lagares-Garcia J, Vrees M, Klipfel A, Cataldo T, Sikov W, McNulty B, Shipley J, Anderson E, Khurshid H, Oconnor B, Oldenburg NB, Radie-Keane K, Husain S, Safran H. Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer. Int J Radiat Oncol Biol Phys 2012, 82(1):124-129.
30. 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):824-830.
31. Willett CG, Duda DG, Ancukiewicz M, Shah M, Czito BG, Bentley R, Poleski M, Fujita H, Lauwers GY, Carroll M, Tyler D, Mantyh C, Shellito P, Chung DC, Clark JW, Jain RK. A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer. Oncologist 2010, 15(8):845-851.
32. 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, Wong 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):3020-3026.
33. 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):472-478.
34. Winkler J, Zipp L, Knoblich J, Zimmermann F. Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer, Treatment outcome outside clinical trials. Strahlenther Onkol 2012, 188(5):377-382.
35. Ofner D, Devries AF, Schaberl-Moser R, Greil R, Rabl H, Tschmelitsch J, Zitt M, Kapp KS, Fastner G, Keil F, Eisterer W, Jäger R, Offner F, Gnant M, Thaler J. TAKO 05/ABCSG R-02 Trial Investigators. Preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with newly diagnosed, primary operable, cT3NxM0, low rectal cancer: a phase II study. Strahlenther Onkol 2011, 187(2):100-107.
36. Blazer DG, Kishi Y, Maru DM, Kopetz S, Chun YS, Overman MJ, Fogelman D, Eng C, Chang DZ, Wang H, Zorzi D, Ribero D, Ellis LM, Glover KY, Wolff RA, Curley SA, Abdalla EK, Vauthey JN. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol 2008, 26(33):5344-5351.
37. Kishi Y, Zorzi D, Contreras CM, Maru DM, Kopetz S, Ribero D, Motta M, Ravarino N, Risio M, Curley SA, Abdalla EK, Capussotti L, Vauthey JN. Extended preoperative chemotherapy does not improve pathologic response and increases postoperative liver insufficiency after hepatic resection for colorectal liver metastases. Ann Surg Oncol 2010, 17(11):2870-2876.
38. Ribero D, Wang H, Donadon M, Zorzi D, Thomas MB, Eng C, Chang DZ, Curley SA, Abdalla EK, Ellis LM, Vauthey JN. Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases. Cancer 2007, 110(12):2761-2767.
39. Klinger M, Tamandl D, Eipeldauer S, Hacker S, Herberger B, Kaczirek K, Dorfmeister M, Gruenberger B, Gruenberger T. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol 2010, 17(8):2059-2065.
40. Bear HD, Tang G, Rastogi P, Geyer CE, Robidoux A, Atkins JN, Baez L, Brufsky A, Mehta RS, Fehrenbacher L, Pajon ER, Senecal FM, Gaur R, Margolese RG, Adams PT, Gross HM, Swain SM, Mamounas EP, Costantino JP, Wolmark N. The effect on pCR of bevacizumab and/or antimetabolites added to standard neoadjuvant chemotherapy: NSABP protocol B-40. J Clin Oncol 2011, 29:ASCO 2011. suppl; abstr LBA1005.
41. von Minckwitz G, Eidtmann H, Rezai M, Fasching PA, Tesch H, Eggemann H, Schrader I, Kittel K, Hanusch C, Kreienberg R, Solbach C, Gerber B, Jackisch C, Kunz G, Blohmer JU, Huober J, Hauschild M, Fehm T, Müller BM, Denkert C, Loibl S, Nekljudova V, Untch M. German Breast Group; Arbeitsgemeinschaft Gynäkologische Onkologie-Breast Study Groups. Neoadjuvant chemotherapy and bevacizumab for HER2-negative breast cancer. N Engl J Med 2012, 366(4):299-309.
42. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 2011, 29(1):11-16.
43. de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, André T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 2012, 13(12):1225-1233.
44. Dewdney A, Cunningham D, Tabernero J, Capdevila J, Glimelius B, Cervantes A, Tait D, Brown G, Wotherspoon A, Gonzalez De Castro D, Chua YJ, Wong R, Barbachano Y, Oates J, Chau I. Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol 2012, 30(14):1620-1627.