Skip to main content
Erschienen in: Annals of Surgical Oncology 4/2014

01.04.2014 | Colorectal Cancer

Analysis of Bevacizumab-based Preoperative Radiochemotherapy in Patients with Locally Advanced Rectal Cancer on Surgery-associated Spectrum of Complications

verfasst von: Kathrin Dellas, Johannes Buller, Gregor Jürgen Görtz, Michael Richter, Thomas Höhler, Dirk Arnold, Tobias Keck, Jürgen Dunst, Helmut Zühlke

Erschienen in: Annals of Surgical Oncology | Ausgabe 4/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

Preoperative radiochemotherapy (RCT) is a standard of care for patients with locally advanced rectal cancer (LARC; stages II and III). Results of our phase II study (BevXelOx-RT) have shown that this regimen is feasible but without a significant improvement of pathological complete response. Whether preoperatively administered bevacizumab, due to its specific toxicity profile, leads to increased rates of surgical complications is currently a subject for debate. This analysis focusses on the surgery-associated spectrum of complications.

Methods

Data from 62 patients with rectal cancer (uT3-4; N0/1, M0) of the phase II trial were analyzed. Patients received radiotherapy (50.4/1.8 Gy fractions), simultaneous bevacizumab 5 mg/kg (d1, d15, d29), and capecitabine 825 mg/m2 twice daily (d1–14, d22–35), oxaliplatin 50 mg/m2 (d1, d8, d22, d29). Four to six weeks after RCT, surgical resection was performed.

Results

Overall, 69/69 patients underwent surgery, and 66 (95.7 %) patients had R0 resection. Surgery was mainly conducted (in 66 %) by highly experienced surgeons (>20 resections of rectal cancer/year) with differences between the institutions due to the operative procedures but without effects on the rate of R0 resection or complications. The average duration of surgery was 239 min (±10). Frequency of multivisceral resections (11 %), intraoperative (8 %) and postoperative (43 %) complications were all in the expected range. In particular, we did not observe an increased rate of postoperative bleedings (3 %). The postoperative mortality rate was 0 %.

Conclusions

Quantity and the kind of surgery-associated spectrum of complications followed by a preoperative bevacizumab-containing RCT regimen in patients with LARC were in line with comparable trials of bevacizumab-based approaches.
Literatur
1.
Zurück zum Zitat Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13(6):579-88.PubMedCrossRef Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, et al. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13(6):579-88.PubMedCrossRef
2.
Zurück zum Zitat Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-1123.PubMedCrossRef Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, et al. EORTC Radiotherapy Group Trial 22921. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355(11):1114-1123.PubMedCrossRef
3.
Zurück zum Zitat Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. 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.PubMedCrossRef Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, et al. 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.PubMedCrossRef
4.
Zurück zum Zitat Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731-1740.PubMedCrossRef Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, et al. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731-1740.PubMedCrossRef
5.
Zurück zum Zitat Velenik V, Ocvirk J, Music M, Bracko M, Anderluh F, Oblak I, et al. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study. Radiat Oncol. 2011;6:105.PubMedCentralPubMedCrossRef Velenik V, Ocvirk J, Music M, Bracko M, Anderluh F, Oblak I, et al. Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer: results of an open-label phase II study. Radiat Oncol. 2011;6:105.PubMedCentralPubMedCrossRef
6.
Zurück zum Zitat Kennecke H, Berry S, Wong R, Zhou C, Tankel K, Easaw J, et al. 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.PubMedCrossRef Kennecke H, Berry S, Wong R, Zhou C, Tankel K, Easaw J, et al. 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.PubMedCrossRef
7.
Zurück zum Zitat Dipetrillo T, Pricolo V, Lagares-Garcia J, Vrees M, Klipfel A, Cataldo T, et al. Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2012;82(1):124-9.PubMedCrossRef Dipetrillo T, Pricolo V, Lagares-Garcia J, Vrees M, Klipfel A, Cataldo T, et al. Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2012;82(1):124-9.PubMedCrossRef
8.
Zurück zum Zitat Crane CH, Eng C, Feig BW, Das P, Skibber JM, Chang GJ, et al. 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.PubMedCrossRef Crane CH, Eng C, Feig BW, Das P, Skibber JM, Chang GJ, et al. 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.PubMedCrossRef
9.
Zurück zum Zitat Willett CG, Duda DG, Ancukiewicz M, Shah M, Czito BG, Bentley R, et al. 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):845-51.PubMedCentralPubMedCrossRef Willett CG, Duda DG, Ancukiewicz M, Shah M, Czito BG, Bentley R, et al. 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):845-51.PubMedCentralPubMedCrossRef
10.
Zurück zum Zitat Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, et al. 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.PubMedCentralPubMedCrossRef Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, et al. 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.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, et al. 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.PubMedCrossRef Czito BG, Bendell JC, Willett CG, Morse MA, Blobe GC, Tyler DS, et al. 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.PubMedCrossRef
12.
Zurück zum Zitat Dellas K, Höhler T, Reese T, Würschmidt F, Engel E, Rödel C, et al. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer. Radiat Oncol. 2013;8(1):90.PubMedCentralPubMedCrossRef Dellas K, Höhler T, Reese T, Würschmidt F, Engel E, Rödel C, et al. Phase II trial of preoperative radiochemotherapy with concurrent bevacizumab, capecitabine and oxaliplatin in patients with locally advanced rectal cancer. Radiat Oncol. 2013;8(1):90.PubMedCentralPubMedCrossRef
13.
Zurück zum Zitat Arnold D, Seufferlein T. Targeted treatments in colorectal cancer: state of the art and future perspectives: Gut. 2010;59(6):838-58.PubMedCrossRef Arnold D, Seufferlein T. Targeted treatments in colorectal cancer: state of the art and future perspectives: Gut. 2010;59(6):838-58.PubMedCrossRef
14.
Zurück zum Zitat Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91(3):173-80.PubMedCrossRef Scappaticci FA, Fehrenbacher L, Cartwright T, Hainsworth JD, Heim W, Berlin J, et al. Surgical wound healing complications in metastatic colorectal cancer patients treated with bevacizumab. J Surg Oncol. 2005;91(3):173-80.PubMedCrossRef
15.
Zurück zum Zitat Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26(32):5254-60.PubMedCrossRef Kesmodel SB, Ellis LM, Lin E, Chang GJ, Abdalla EK, Kopetz S, et al. Preoperative bevacizumab does not significantly increase postoperative complication rates in patients undergoing hepatic surgery for colorectal cancer liver metastases. J Clin Oncol. 2008;26(32):5254-60.PubMedCrossRef
16.
Zurück zum Zitat Gruenberger T, Arnold D, Rubbia-Brandt L. Pathologic response to bevacizumab-containing chemotherapy in patients with colorectal liver metastases and its correlation with survival. Surg Oncol. 2012;21(4):309-15.PubMedCrossRef Gruenberger T, Arnold D, Rubbia-Brandt L. Pathologic response to bevacizumab-containing chemotherapy in patients with colorectal liver metastases and its correlation with survival. Surg Oncol. 2012;21(4):309-15.PubMedCrossRef
17.
Zurück zum Zitat Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19-23.PubMedCrossRef Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19-23.PubMedCrossRef
18.
Zurück zum Zitat Landry JC, Feng Y, Cohen SJ, Staley CA 3rd, Whittington R, Sigurdson ER, et al. Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204. Cancer. 2013;119(8):1521-27.PubMedCrossRef Landry JC, Feng Y, Cohen SJ, Staley CA 3rd, Whittington R, Sigurdson ER, et al. Phase 2 study of preoperative radiation with concurrent capecitabine, oxaliplatin, and bevacizumab followed by surgery and postoperative 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX), and bevacizumab in patients with locally advanced rectal cancer: ECOG 3204. Cancer. 2013;119(8):1521-27.PubMedCrossRef
19.
Zurück zum Zitat Liang JT, Lai HS, Cheng KW. Technical feasibility of laparoscopic total mesorectal excision for patients with low rectal cancer after concurrent radiation and chemotherapy with bevacizumab plus FOLFOX. Surg Endosc. 2011;25(1):305-8.PubMedCrossRef Liang JT, Lai HS, Cheng KW. Technical feasibility of laparoscopic total mesorectal excision for patients with low rectal cancer after concurrent radiation and chemotherapy with bevacizumab plus FOLFOX. Surg Endosc. 2011;25(1):305-8.PubMedCrossRef
20.
Zurück zum Zitat Marusch F, Gastinger I, Schneider C, Scheidbach H, Konradt J, Bruch HP, et al. Laparoscopic Colorectal Surgery Study Group (LCSSG). Experience as a factor influencing the indications for laparoscopic colorectal surgery and the results. Surg Endosc. 2001;15(2):116-120.PubMedCrossRef Marusch F, Gastinger I, Schneider C, Scheidbach H, Konradt J, Bruch HP, et al. Laparoscopic Colorectal Surgery Study Group (LCSSG). Experience as a factor influencing the indications for laparoscopic colorectal surgery and the results. Surg Endosc. 2001;15(2):116-120.PubMedCrossRef
21.
Zurück zum Zitat Kim JS, Hur H, Kim NK, Kim YW, Cho SY, Kim JY, et al. Oncologic outcomes after radical surgery following preoperative chemoradiotherapy for locally advanced lower rectal cancer: abdominoperineal resection versus sphincter-preserving procedure. Ann Surg Oncol. 2009;(16):1266-1273.PubMedCrossRef Kim JS, Hur H, Kim NK, Kim YW, Cho SY, Kim JY, et al. Oncologic outcomes after radical surgery following preoperative chemoradiotherapy for locally advanced lower rectal cancer: abdominoperineal resection versus sphincter-preserving procedure. Ann Surg Oncol. 2009;(16):1266-1273.PubMedCrossRef
22.
Zurück zum Zitat 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;21(16):3098-3104.PubMedCrossRef 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;21(16):3098-3104.PubMedCrossRef
23.
Zurück zum Zitat Rödel C, Liersch T, Hermann RM, Arnold D, Reese T, Hipp M, et al. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol. 2007;25(1):110-117.PubMedCrossRef Rödel C, Liersch T, Hermann RM, Arnold D, Reese T, Hipp M, et al. Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol. 2007;25(1):110-117.PubMedCrossRef
24.
Zurück zum Zitat Chessin DB, Enker W, Cohen AM, Paty PB, Weiser MR, Saltz L, et al. Complications after preoperative combined modality therapy and radical resection of locally advanced rectal cancer: a 14-year experience from a specialty service. J Am Coll Surg. 2005;200(6):876-882.PubMedCrossRef Chessin DB, Enker W, Cohen AM, Paty PB, Weiser MR, Saltz L, et al. Complications after preoperative combined modality therapy and radical resection of locally advanced rectal cancer: a 14-year experience from a specialty service. J Am Coll Surg. 2005;200(6):876-882.PubMedCrossRef
25.
Zurück zum Zitat Hospers GA, Punt CJA, Tesselaar ME, Cats A, Havenga K, Leer JW, et al. Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer: a phase I–II multicenter sdtudy of the Dutch Colorectal Cancer Group. Ann Surg Oncol. 2007;14(10):2773–2779.PubMedCentralPubMedCrossRef Hospers GA, Punt CJA, Tesselaar ME, Cats A, Havenga K, Leer JW, et al. Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer: a phase I–II multicenter sdtudy of the Dutch Colorectal Cancer Group. Ann Surg Oncol. 2007;14(10):2773–2779.PubMedCentralPubMedCrossRef
26.
Zurück zum Zitat Swellengrebel HA, Marijnen CA, Verwaal VJ, Vincent A, Heuff G, Gerhards MF, et al. Toxicity and complications of preoperative chemoradiotherapy for locally advanced rectal cancer. Br J Surg. 2011;98(3):418-426.PubMedCrossRef Swellengrebel HA, Marijnen CA, Verwaal VJ, Vincent A, Heuff G, Gerhards MF, et al. Toxicity and complications of preoperative chemoradiotherapy for locally advanced rectal cancer. Br J Surg. 2011;98(3):418-426.PubMedCrossRef
Metadaten
Titel
Analysis of Bevacizumab-based Preoperative Radiochemotherapy in Patients with Locally Advanced Rectal Cancer on Surgery-associated Spectrum of Complications
verfasst von
Kathrin Dellas
Johannes Buller
Gregor Jürgen Görtz
Michael Richter
Thomas Höhler
Dirk Arnold
Tobias Keck
Jürgen Dunst
Helmut Zühlke
Publikationsdatum
01.04.2014
Verlag
Springer US
Erschienen in
Annals of Surgical Oncology / Ausgabe 4/2014
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-013-3412-9

Weitere Artikel der Ausgabe 4/2014

Annals of Surgical Oncology 4/2014 Zur Ausgabe

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.