Pre-operative chemoradiotherapy in locally advanced rectal cancer: Capecitabine versus Capox
Abstract
Introduction: Pre-operative chemoradiotherapy is considered a standard approach for TNM stage II-III rectal cancer. The aim of this study was to investigate the effectiveness and toxicity of pre-operative chemoradiation in this setting.
Methods: Between January 2007 and January 2011, patients received 5 weeks of treatment with radiotherapy 50.4/54 Gy/25 or 30 fractions with concurrent capecitabine 850 mg/m2 twice daily 5 days per week (CAP) or radiotherapy 50.4/54 Gy/25 fractions with capecitabine 850 mg/m2 twice daily 5 days per week and oxaliplatin 50 mg/m(2) once weekly (CAPOX). Histopathologic tumor regression (TRG) was determined by the amount of viable tumor versus fibrosis. Toxicity was monitored according to the Common Toxicity Criteria of the National Cancer Institute.
Results: Seventy six patients were included (median age 68.3 years [range 45-88], 67% male). Median tumor distance from anal verge was 7cm (range 2-13). CAP treatment was performed in 67% and CAPOX in 33% of patients. Pathologic complete response was achieved in 13,2%. T- and N- downstaging rates were 52.6%, 65.8%, respectively. Grade 3 toxicity was documented in less than 10% of patients and no grade 4 toxicity was observed.
Conclusions: This study suggests that there is no major benefit from adding oxaliplatin to preoperative chemoradiotherapy with capecitabine.
Keywords: rectal cancer, chemoradiotherapy, downstaging, capecitabine, oxaliplatin
Downloads
Download data is not yet available.
References
Pontes L, Silva M, Matoso F: Registo Oncológico Nacional 2005. Instituto Português de Oncologia de Lisboa 2009
Siegel R, Ward E, Brawley O et al: Cancer Statistics 2011: The impact of eliminating socioeconomic and racial disparities on premature
cancer deaths. CA Cancer J Clin 2011
Cheng L, Eng C, Nieman LZ et al: Trend in Colorectal Cancer Incidence by Anatomic Site and Disease Stage in United States From 1995
and 2005. Am J Clin Oncol 2011
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; 17:361-371
Edge SBB, Compton C, Fritz A, Grenne F, Trotti A: AJCC Cancer Staging Manual (7th Edition). New York, Springer 2010
Velenik V, Ocvirk J, Music M et al: Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer:
results of an open-label phase II study. Radiation Oncology 2011; 6:105
Cecil DT, Sexton R, Moran BJ, Heald RJ: Total mesorectal excision results in low local recurrence rates in lymph node-positive
rectal cancer. Dis Colon Rectum 2004; 47: 1145-1150
Kapiteijn E, Marijnen Cam, Nagtegaal ID et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal
cancer. N Engl J Med 2001; 345: 638-646
Rödel C, Martus P, Papadoupolos T et al: Prognostic Significance of Tumor Regression After Preoperative Chemoradiotherapy for Rectal
Cancer. J Clin Oncol 2005; 23:8688-8696
Sauer R, Becker H, Hohenberger W et al: For the German Rectal Cancer Study Group. Preoperative versus postoperative chemoradio-
therapy for rectal cancer. N Engl J Med 2004; 351: 1731-1740
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?. British Journal of Cancer 2006; 94:363-371
Janjan Na, Khoo Vs, Abbruzzese J et al: Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advan-
ced rectal cancer: The M.D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44:1027-1038
Theodoropoulos G, Wise WE, Padmanabhan A, et al: T-level downstaging and complete pathologic response after preoperative chemora-
diation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum 2002; 45:895-903
Kaminsky-Forrett MC, Conroy T, Luporsi E, et al: Prognostic implications of downstaging following preoperative radiation therapy for
operable T3–T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998; 42:935-941
Glynne-Jones R, Mawdsley S, Pearce T, Buyse M: Alternative clinical end points in rectal cancer – are we getting closer?. Annals of
Oncology 2006; 17:1239-1248
Dworak O, Keilholz L, Hoffmann A: Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis
1997; 12:19-23
Hartley A, Ho KF, Mcconkey C, Geh J: Pathological complete response following pre-operative chemoradiotherapy in rectal cancer:
analysis of phase II/III trials. The British Journal of Radiology 2005; 78:934-938
Glimelius B, Pahlman L, Cervantes A et al: Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Annals of Oncology 2010; 21 (suppl 5)
Roh Ms, Yothers GA, O’Connell M et al: 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):3503
Collette L, Bosset J-F, Den Dulk M et al: Patients with curative resection of cT3-T4 rectal cancer after preoperative radiotherapy or
radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organization for Research
and Treatment of Cancer radiation Oncology Group. J Clin Oncol 2007; 25:4379-4386
Koeberle D, Burkhard R, Von Moos R et al: Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preope-
rative pelvic radiotherapy in patients with locally advanced rectal cancer. British Journal of Cancer 2008; 98: 1204-1209
Machiels JP, Duck L, Honhon B et al: Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients
with rectal cancer: the RadiOxCape study. Ann Oncol 2005; 16: 1898-1905
Rutten H, Sebag-Montefiore D, Glynne-Jones R et al: 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; 24 (18S):
(abstract 3528)
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: 3098-3104
RödeL C, Liersch T, Hermann RM et al: Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer, J Clin Oncol 2007;
25:110-117
Devita V., Lawrence T, Rosenberg S: Cancer, Principles & Practice of Oncology (8th edition), Philadelphia, Lippincott Williams & Wilkins
2008, vol. 1
Valentini V, Coco C, Cellini N et al: Preoperative Chemoradiation with Cisplatin and 5-Fluorouracil for Extraperitoneal T3 Rectal
Cancer: Acute Toxicity, Tumor Response, Sphincter Preservation. Int J Radiation Oncology Biol Phys. 2002; 54:403-408
Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH: Preoperative Chemoradiation Using Oral Capecitabine in Locally Advanced Rectal Cancer.
Int J Radiation Oncology Biol Phys 2002; Vol. 54:403-408
Díaz-Gonzalez J, Calvo F, Cortés J et al: Preoperative Chemoradiation with oral Tegafur within Multidisciplinary Therapeutic Approach in Patients with T3-4 Rectal Cancer. Int J Radiation Oncology Biol Phys. 2002; 61:1378-1384
Haller D, Cassidy J, Clarke S et al: Tolerability od fluoropyrimidines appears to differ by region. Proceedings of 2006 ASCO Meeting Part I. J Clin Oncol 2006; 24 (Suppl.)
Kim G, Colangelo L, Wieand H et al: Prognostic and Predictive Roles of High-Degree Microsatellite Instability in Colon Cancer: A National Cancer Institute–National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 2007; 25:767-772
Meyers M, Wagner MW, Hwang HS, Kinsella T, Boothman D: Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 2001; 61:5193-5201
Carethers JM, Chauhan DP, Fink D et al: Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999; 117:123-131
Siegel R, Ward E, Brawley O et al: Cancer Statistics 2011: The impact of eliminating socioeconomic and racial disparities on premature
cancer deaths. CA Cancer J Clin 2011
Cheng L, Eng C, Nieman LZ et al: Trend in Colorectal Cancer Incidence by Anatomic Site and Disease Stage in United States From 1995
and 2005. Am J Clin Oncol 2011
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; 17:361-371
Edge SBB, Compton C, Fritz A, Grenne F, Trotti A: AJCC Cancer Staging Manual (7th Edition). New York, Springer 2010
Velenik V, Ocvirk J, Music M et al: Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally advanced rectal cancer:
results of an open-label phase II study. Radiation Oncology 2011; 6:105
Cecil DT, Sexton R, Moran BJ, Heald RJ: Total mesorectal excision results in low local recurrence rates in lymph node-positive
rectal cancer. Dis Colon Rectum 2004; 47: 1145-1150
Kapiteijn E, Marijnen Cam, Nagtegaal ID et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal
cancer. N Engl J Med 2001; 345: 638-646
Rödel C, Martus P, Papadoupolos T et al: Prognostic Significance of Tumor Regression After Preoperative Chemoradiotherapy for Rectal
Cancer. J Clin Oncol 2005; 23:8688-8696
Sauer R, Becker H, Hohenberger W et al: For the German Rectal Cancer Study Group. Preoperative versus postoperative chemoradio-
therapy for rectal cancer. N Engl J Med 2004; 351: 1731-1740
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?. British Journal of Cancer 2006; 94:363-371
Janjan Na, Khoo Vs, Abbruzzese J et al: Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advan-
ced rectal cancer: The M.D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999; 44:1027-1038
Theodoropoulos G, Wise WE, Padmanabhan A, et al: T-level downstaging and complete pathologic response after preoperative chemora-
diation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum 2002; 45:895-903
Kaminsky-Forrett MC, Conroy T, Luporsi E, et al: Prognostic implications of downstaging following preoperative radiation therapy for
operable T3–T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998; 42:935-941
Glynne-Jones R, Mawdsley S, Pearce T, Buyse M: Alternative clinical end points in rectal cancer – are we getting closer?. Annals of
Oncology 2006; 17:1239-1248
Dworak O, Keilholz L, Hoffmann A: Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis
1997; 12:19-23
Hartley A, Ho KF, Mcconkey C, Geh J: Pathological complete response following pre-operative chemoradiotherapy in rectal cancer:
analysis of phase II/III trials. The British Journal of Radiology 2005; 78:934-938
Glimelius B, Pahlman L, Cervantes A et al: Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Annals of Oncology 2010; 21 (suppl 5)
Roh Ms, Yothers GA, O’Connell M et al: 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):3503
Collette L, Bosset J-F, Den Dulk M et al: Patients with curative resection of cT3-T4 rectal cancer after preoperative radiotherapy or
radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organization for Research
and Treatment of Cancer radiation Oncology Group. J Clin Oncol 2007; 25:4379-4386
Koeberle D, Burkhard R, Von Moos R et al: Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preope-
rative pelvic radiotherapy in patients with locally advanced rectal cancer. British Journal of Cancer 2008; 98: 1204-1209
Machiels JP, Duck L, Honhon B et al: Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients
with rectal cancer: the RadiOxCape study. Ann Oncol 2005; 16: 1898-1905
Rutten H, Sebag-Montefiore D, Glynne-Jones R et al: 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; 24 (18S):
(abstract 3528)
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: 3098-3104
RödeL C, Liersch T, Hermann RM et al: Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer, J Clin Oncol 2007;
25:110-117
Devita V., Lawrence T, Rosenberg S: Cancer, Principles & Practice of Oncology (8th edition), Philadelphia, Lippincott Williams & Wilkins
2008, vol. 1
Valentini V, Coco C, Cellini N et al: Preoperative Chemoradiation with Cisplatin and 5-Fluorouracil for Extraperitoneal T3 Rectal
Cancer: Acute Toxicity, Tumor Response, Sphincter Preservation. Int J Radiation Oncology Biol Phys. 2002; 54:403-408
Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH: Preoperative Chemoradiation Using Oral Capecitabine in Locally Advanced Rectal Cancer.
Int J Radiation Oncology Biol Phys 2002; Vol. 54:403-408
Díaz-Gonzalez J, Calvo F, Cortés J et al: Preoperative Chemoradiation with oral Tegafur within Multidisciplinary Therapeutic Approach in Patients with T3-4 Rectal Cancer. Int J Radiation Oncology Biol Phys. 2002; 61:1378-1384
Haller D, Cassidy J, Clarke S et al: Tolerability od fluoropyrimidines appears to differ by region. Proceedings of 2006 ASCO Meeting Part I. J Clin Oncol 2006; 24 (Suppl.)
Kim G, Colangelo L, Wieand H et al: Prognostic and Predictive Roles of High-Degree Microsatellite Instability in Colon Cancer: A National Cancer Institute–National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 2007; 25:767-772
Meyers M, Wagner MW, Hwang HS, Kinsella T, Boothman D: Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 2001; 61:5193-5201
Carethers JM, Chauhan DP, Fink D et al: Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 1999; 117:123-131
Published
2014-01-31
How to Cite
BARATA, Pedro C. et al.
Pre-operative chemoradiotherapy in locally advanced rectal cancer: Capecitabine versus Capox.
Revista Portuguesa de Cirurgia, [S.l.], n. 27, p. 11-18, jan. 2014.
ISSN 2183-1165.
Available at: <https://revista.spcir.com/index.php/spcir/article/view/328>. Date accessed: 03 july 2024.
Section
Original Papers
