Skip to main content
Top
Published in: World Journal of Surgical Oncology 1/2009

Open Access 01-12-2009 | Research

Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial

Authors: Mostafa Abd Elwanis, Doaa W. Maximous, Mohamed Ibrahim Elsayed, Nabiel N. H. Mikhail

Published in: World Journal of Surgical Oncology | Issue 1/2009

Login to get access

Abstract

Introduction

Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery.

Aim

To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine.

Patients and methods

This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique.

Results

Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively.

Conclusion

In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate.
Appendix
Available only for authorised users
Literature
1.
go back to reference Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wigger T: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001, 345: 638-46. 10.1056/NEJMoa010580.CrossRefPubMed Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wigger T: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001, 345: 638-46. 10.1056/NEJMoa010580.CrossRefPubMed
2.
go back to reference Wiggers T, Velde van de CJ: The circumferential margin in rectal cancer. Recommendations based on the Dutch Total Mesorectal Excision Study. Eur J Cancer. 2002, 38: 973-6. 10.1016/S0959-8049(02)00054-0.CrossRefPubMed Wiggers T, Velde van de CJ: The circumferential margin in rectal cancer. Recommendations based on the Dutch Total Mesorectal Excision Study. Eur J Cancer. 2002, 38: 973-6. 10.1016/S0959-8049(02)00054-0.CrossRefPubMed
3.
go back to reference Dahlberg M, Sternberg A, Pahlman L, Glimelius S: Cost effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial. Int J Radiat Oncol Biol Phys. 2002, 54: 654-60.CrossRefPubMed Dahlberg M, Sternberg A, Pahlman L, Glimelius S: Cost effectiveness of preoperative radiotherapy in rectal cancer: results from the Swedish Rectal Cancer Trial. Int J Radiat Oncol Biol Phys. 2002, 54: 654-60.CrossRefPubMed
4.
go back to reference Glimelius B, Isacsson U, Jung B, Pahlman L: Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose response effect favouring preoperative treatment. Int J Radiat Oncol Biol Phys. 1997, 37: 281-7.CrossRefPubMed Glimelius B, Isacsson U, Jung B, Pahlman L: Radiotherapy in addition to radical surgery in rectal cancer: evidence for a dose response effect favouring preoperative treatment. Int J Radiat Oncol Biol Phys. 1997, 37: 281-7.CrossRefPubMed
5.
go back to reference Valentini V, Glimelius B, Minsky B, Van Cutsem E, Batelink H, Beets-Tan RG, Gerard JP: The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas with support the need for an European consensus. Radiother Oncol. 2005, 76: 241-50. 10.1016/j.radonc.2005.07.001.CrossRefPubMed Valentini V, Glimelius B, Minsky B, Van Cutsem E, Batelink H, Beets-Tan RG, Gerard JP: The multidisciplinary rectal cancer treatment: main convergences, controversial aspects and investigational areas with support the need for an European consensus. Radiother Oncol. 2005, 76: 241-50. 10.1016/j.radonc.2005.07.001.CrossRefPubMed
6.
go back to reference Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely V, Zerbib F: Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule. Ann Surg. 2005, 241: 465-69. 10.1097/01.sla.0000154551.06768.e1.PubMedCentralCrossRefPubMed Rullier E, Laurent C, Bretagnol F, Rullier A, Vendrely V, Zerbib F: Sphincter-saving resection for all rectal carcinomas: the end of the 2-cm distal rule. Ann Surg. 2005, 241: 465-69. 10.1097/01.sla.0000154551.06768.e1.PubMedCentralCrossRefPubMed
7.
go back to reference 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: 291-7. 10.1007/s002800050043.CrossRefPubMed 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: 291-7. 10.1007/s002800050043.CrossRefPubMed
8.
go back to reference Sawada N, Ishikawa T, Sekiguchi F, 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.PubMed Sawada N, Ishikawa T, Sekiguchi F, 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.PubMed
9.
go back to reference Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shim-ma N, Umeda I, Ishitsuka H: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998, 34: 1274-81. 10.1016/S0959-8049(98)00058-6.CrossRefPubMed Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shim-ma N, Umeda I, Ishitsuka H: Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998, 34: 1274-81. 10.1016/S0959-8049(98)00058-6.CrossRefPubMed
10.
go back to reference De Bruin AF, Nuyttens JJ, Ferenschild FT, Planting AS, Verhoef C, De Wilt JH: Preoperative chemoradiation with capecitabine in locally advanced rectal cancer. Netherlands Journal of Medicine. 2008, 66: 71-76.PubMed De Bruin AF, Nuyttens JJ, Ferenschild FT, Planting AS, Verhoef C, De Wilt JH: Preoperative chemoradiation with capecitabine in locally advanced rectal cancer. Netherlands Journal of Medicine. 2008, 66: 71-76.PubMed
11.
go back to reference 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?. Annals of Oncology. 2006, 17: 361-71. 10.1093/annonc/mdj052.CrossRefPubMed 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?. Annals of Oncology. 2006, 17: 361-71. 10.1093/annonc/mdj052.CrossRefPubMed
12.
go back to reference Desai SP, El-Rayes BF, Ben-Josef E, Greenson JK, Knol JA, Huang EH, Griffith KA, Philip PA, McGinn CJ, Zalupski MM: A Phase II Study of Preoperative Capecitabine and Radiation Therapy in Patients With Rectal Cancer. Am J Clin Oncol. 2007, 30: 340-5. 10.1097/COC.0b013e318033ed63.CrossRefPubMed Desai SP, El-Rayes BF, Ben-Josef E, Greenson JK, Knol JA, Huang EH, Griffith KA, Philip PA, McGinn CJ, Zalupski MM: A Phase II Study of Preoperative Capecitabine and Radiation Therapy in Patients With Rectal Cancer. Am J Clin Oncol. 2007, 30: 340-5. 10.1097/COC.0b013e318033ed63.CrossRefPubMed
13.
go back to reference Enker WE, Thaler HT, Cranor ML, Polyak T: Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg. 1995, 181: 335-46.PubMed Enker WE, Thaler HT, Cranor ML, Polyak T: Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg. 1995, 181: 335-46.PubMed
14.
go back to reference Wheeler JM, Dodds E, Warren BF, Cunningham C, George BD, Jones AC, Mortensen NJ: Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: Correlation with rectal cancer regression grade. Dis Colon Rectum. 2004, 47: 2025-31. 10.1007/s10350-004-0713-x.CrossRefPubMed Wheeler JM, Dodds E, Warren BF, Cunningham C, George BD, Jones AC, Mortensen NJ: Preoperative chemoradiotherapy and total mesorectal excision surgery for locally advanced rectal cancer: Correlation with rectal cancer regression grade. Dis Colon Rectum. 2004, 47: 2025-31. 10.1007/s10350-004-0713-x.CrossRefPubMed
15.
go back to reference Lawrence TS, Tepper JE, Blackstok AW: Fluoropyrimidineradiation interactions in cells and tumors. Semin Radiat Oncol. 1997, 7: 260-6. 10.1016/S1053-4296(97)80024-0.CrossRefPubMed Lawrence TS, Tepper JE, Blackstok AW: Fluoropyrimidineradiation interactions in cells and tumors. Semin Radiat Oncol. 1997, 7: 260-6. 10.1016/S1053-4296(97)80024-0.CrossRefPubMed
16.
go back to reference Rich TA: Irradiation Plus 5-Flurouracil: Cellular mechanisms of action and treatment schedules. Semin Radiat Oncol. 1997, 7: 267-73. 10.1016/S1053-4296(97)80025-2.CrossRefPubMed Rich TA: Irradiation Plus 5-Flurouracil: Cellular mechanisms of action and treatment schedules. Semin Radiat Oncol. 1997, 7: 267-73. 10.1016/S1053-4296(97)80025-2.CrossRefPubMed
17.
go back to reference Galmarini CM, Mackey JR, Dumontet C: Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol. 2002, 3: 415-24. 10.1016/S1470-2045(02)00788-X.CrossRefPubMed Galmarini CM, Mackey JR, Dumontet C: Nucleoside analogues and nucleobases in cancer treatment. Lancet Oncol. 2002, 3: 415-24. 10.1016/S1470-2045(02)00788-X.CrossRefPubMed
18.
go back to reference Harewood GC, Wiersema MJ: Cost-effectiveness of endoscopic ultrasonography in the evaluation of proximal rectal cancer. Am J Gastroenterol. 2002, 97: 874-878. 10.1111/j.1572-0241.2002.05603.x.CrossRefPubMed Harewood GC, Wiersema MJ: Cost-effectiveness of endoscopic ultrasonography in the evaluation of proximal rectal cancer. Am J Gastroenterol. 2002, 97: 874-878. 10.1111/j.1572-0241.2002.05603.x.CrossRefPubMed
19.
go back to reference Bianchi PP, Ceriani C, Rottoli M, Torzilli G, Pompili G, Malesci A, Ferraroni M, Montorsi M: Endoscopic ultrasonography and magnetic resonance in preoperative staging of rectal cancer: comparison with histologic findings. J Gastrointest Surg. 2005, 9: 1222-7. 10.1016/j.gassur.2005.07.008.CrossRefPubMed Bianchi PP, Ceriani C, Rottoli M, Torzilli G, Pompili G, Malesci A, Ferraroni M, Montorsi M: Endoscopic ultrasonography and magnetic resonance in preoperative staging of rectal cancer: comparison with histologic findings. J Gastrointest Surg. 2005, 9: 1222-7. 10.1016/j.gassur.2005.07.008.CrossRefPubMed
20.
go back to reference Bianchi P, Ceriani C, Palmisano A, Pompili G, Passoni GR, Rottoli M, Cappellani A, Montorsi M: A prospective comparison of endorectal ultrasound and pelvic magnetic resonance in the preoperative staging of rectal cancer. Ann Ital Chir. 2006, 77: 41-46.PubMed Bianchi P, Ceriani C, Palmisano A, Pompili G, Passoni GR, Rottoli M, Cappellani A, Montorsi M: A prospective comparison of endorectal ultrasound and pelvic magnetic resonance in the preoperative staging of rectal cancer. Ann Ital Chir. 2006, 77: 41-46.PubMed
21.
go back to reference 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: Capcitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol. 2006, 17: 246-51. 10.1093/annonc/mdj041.CrossRefPubMed 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: Capcitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol. 2006, 17: 246-51. 10.1093/annonc/mdj041.CrossRefPubMed
22.
go back to reference Dunst J, Reese T, Debuse J, Hoelscher T, Budach W, Rudat V, Wulf J, Mose S, Hinke A: Phase II study of preoperative chemoradiation with capcitabine in rectal cancer. Proc Am Soc Clin Oncol. 2004, 23: 260- Dunst J, Reese T, Debuse J, Hoelscher T, Budach W, Rudat V, Wulf J, Mose S, Hinke A: Phase II study of preoperative chemoradiation with capcitabine in rectal cancer. Proc Am Soc Clin Oncol. 2004, 23: 260-
23.
go back to reference Dunst J, Debuse J, Rudat V, Wulf J, Budach W, Hoelscher T, Reese T, Mose S, Roedel C, Zuehlke H, Hinke A: Neoadjuvant capcitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: Mature results of a phase II trial. Strahlenther Onkol. 2008, 184 (8): 450-456. 10.1007/s00066-008-1751-4.CrossRefPubMed Dunst J, Debuse J, Rudat V, Wulf J, Budach W, Hoelscher T, Reese T, Mose S, Roedel C, Zuehlke H, Hinke A: Neoadjuvant capcitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: Mature results of a phase II trial. Strahlenther Onkol. 2008, 184 (8): 450-456. 10.1007/s00066-008-1751-4.CrossRefPubMed
24.
go back to reference Dupuis O, Vie B, Liedo G, Hennequin C, Noirclerc M, Bennamoun M, Jacob JH: Preoperative treatment combining cabcitabine with radiation therapy in rectal cancer: A GERCOR phase II study. Oncology. 2007, 73: 169-76. 10.1159/000127383.CrossRefPubMed Dupuis O, Vie B, Liedo G, Hennequin C, Noirclerc M, Bennamoun M, Jacob JH: Preoperative treatment combining cabcitabine with radiation therapy in rectal cancer: A GERCOR phase II study. Oncology. 2007, 73: 169-76. 10.1159/000127383.CrossRefPubMed
25.
go back to reference 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 capcitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Biol phys. 2005, 63: 346-53. 10.1016/j.ijrobp.2005.05.005.CrossRefPubMed 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 capcitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Biol phys. 2005, 63: 346-53. 10.1016/j.ijrobp.2005.05.005.CrossRefPubMed
26.
go back to reference Lin EH, Skibber J, Eng C, Delcos ME, Crane C, Amos CB, Rodriguez M, Brown T, Wolff R, Abbruzzese JL, Janjan N: A Phase II study of capecitabine and concomitant boost radiotherapy (XRT) in patients with locally advanced rectal cancer (LARC). J Clin Oncol. 2005, 23 (Suppl 16S): 269s- Lin EH, Skibber J, Eng C, Delcos ME, Crane C, Amos CB, Rodriguez M, Brown T, Wolff R, Abbruzzese JL, Janjan N: A Phase II study of capecitabine and concomitant boost radiotherapy (XRT) in patients with locally advanced rectal cancer (LARC). J Clin Oncol. 2005, 23 (Suppl 16S): 269s-
27.
go back to reference Velenik K, Anderluh F, Oblak I, Strojan P, Zakotnik B: Capcitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: Prospective phase II trial. Croat Med J. 2006, 47: 693-700.PubMedCentralPubMed Velenik K, Anderluh F, Oblak I, Strojan P, Zakotnik B: Capcitabine as a radiosensitizing agent in neoadjuvant treatment of locally advanced resectable rectal cancer: Prospective phase II trial. Croat Med J. 2006, 47: 693-700.PubMedCentralPubMed
28.
go back to reference Vedetic G, Fisher B, Perera F, Bauman GS, Kocha WI, Taylor M, Vincent MD, Plewes EA, Engel CJ, Stitt LW: Preoperative radiation with concurrent 5-FU continuous infusion for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 1998, 42: 319-324.CrossRef Vedetic G, Fisher B, Perera F, Bauman GS, Kocha WI, Taylor M, Vincent MD, Plewes EA, Engel CJ, Stitt LW: Preoperative radiation with concurrent 5-FU continuous infusion for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 1998, 42: 319-324.CrossRef
29.
go back to reference Glimelius B: Chemoradiotherapy for rectal cancer-is there an optimal combination?. Ann Oncol. 2001, 12: 1039-45. 10.1023/A:1011628524392.CrossRefPubMed Glimelius B: Chemoradiotherapy for rectal cancer-is there an optimal combination?. Ann Oncol. 2001, 12: 1039-45. 10.1023/A:1011628524392.CrossRefPubMed
30.
go back to reference Beddy D, Hyaland JMP, Winter DC, Lim C, White A, Moriarty M, Armstrong J, Fennelly D, Gibbons D, Sheahan K: A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2008, 15: 3471-7. 10.1245/s10434-008-0149-y.CrossRefPubMed Beddy D, Hyaland JMP, Winter DC, Lim C, White A, Moriarty M, Armstrong J, Fennelly D, Gibbons D, Sheahan K: A simplified tumor regression grade correlates with survival in locally advanced rectal carcinoma treated with neoadjuvant chemoradiotherapy. Ann Surg Oncol. 2008, 15: 3471-7. 10.1245/s10434-008-0149-y.CrossRefPubMed
31.
go back to reference Bujko K, Nowacki M, Nasierowska-Guttmejer A, Michalski W, Bbenek M, Pudeko M, Kryj M, Oldzki J, Szmeja J, Suszniak J: Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiotherapy and Oncology. 2004, 72: 15-24. 10.1016/j.radonc.2003.12.006.CrossRefPubMed Bujko K, Nowacki M, Nasierowska-Guttmejer A, Michalski W, Bbenek M, Pudeko M, Kryj M, Oldzki J, Szmeja J, Suszniak J: Sphincter preservation following preoperative radiotherapy for rectal cancer: report of a randomised trial comparing short-term radiotherapy vs. conventionally fractionated radiochemotherapy. Radiotherapy and Oncology. 2004, 72: 15-24. 10.1016/j.radonc.2003.12.006.CrossRefPubMed
32.
go back to reference Kirshnan S, Janjan NA, Skibber JM, Rodrigues-Bigas MA, Wolff RA, Das P, Delclos ME, Chang GJ, Hope PM, Eng C, Brown TD, Crane CH, Feig BW, Morris J, Vadhan-Raj S, Hamilton SR, Lin EH: Phase II study of capciabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006, 66 (3): 762-771.CrossRef Kirshnan S, Janjan NA, Skibber JM, Rodrigues-Bigas MA, Wolff RA, Das P, Delclos ME, Chang GJ, Hope PM, Eng C, Brown TD, Crane CH, Feig BW, Morris J, Vadhan-Raj S, Hamilton SR, Lin EH: Phase II study of capciabine (Xeloda) and concomitant boost radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006, 66 (3): 762-771.CrossRef
Metadata
Title
Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial
Authors
Mostafa Abd Elwanis
Doaa W. Maximous
Mohamed Ibrahim Elsayed
Nabiel N. H. Mikhail
Publication date
01-12-2009
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2009
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-7-52

Other articles of this Issue 1/2009

World Journal of Surgical Oncology 1/2009 Go to the issue