Journal of Gastrointestinal Cancer

, Volume 43, Issue 4, pp 553–561 | Cite as

Phase II Trial of Concomitant Neoadjuvant Chemotherapy with Oxaliplatin and Capecitabine and Intensity-Modulated Radiotherapy (IMRT) in Rectal Cancer

  • Joan Manel Gasent Blesa
  • Javier Garde Noguera
  • Juan Bautista Laforga Canales
  • Vicent Giner Bosch
  • Antonio Alberola
  • Miguel Soler Tortosa
  • Miguel Peris Godoy
  • Jose Luis Sanchez
  • Mariano Provencio Pulla
  • Vicente Alberola Candel
Original Research


Introduction and Purpose

The purposes of this study are to evaluate the activity and safety of preoperative intensity-modulated radiotherapy and concurrent capecitabine and oxaliplatin (Xelox), the accuracy of preoperative magnetic resonance (MRI) for predicting pathologic results, and the correlation between carcinoembryonic antigen (CEA) and the existence of a pathologic complete response (pCR).

Patients and Methods

Twenty-seven patients (pt) with T3/T4N0/N+ rectal cancer were included. Capecitabine was administered at 825 t.i.d. mg/m2 the days of the radiotherapy (RT), and oxaliplatin was administered weekly at 50 mg/m2. RT was planned to 50.4 Gy. Surgery was scheduled 6 to 8 weeks after completion of Xelox RT. Before the intervention, a pelvic MRI was performed and a CEA level was determined.


After Xelox RT, 7 pt had pCR (26%), 2 pt progression disease, and 18 pt tumor downstaging. Presurgical MRI did not predict the pathological result in 21 pt. Main side effects were diarrhea grade (G) 3 in four pt, hand and foot G1 five Pt and G2 four pt. Paresthesias G1 ten pt, G2 seven pt, and leukopenia six pt G1. Median RT dose was 49.7 Gy (47.5–50.4 Gy). At a mean follow-up of 22.5 months, four pt presented metastatis. Mean pretreatment CEA was 6.8 ng/mL (2.1–17.0). A difference statistically significant when compared pretreatment CEA with presurgical CEA (p < 0.001) was detected. We found a nadir of <5 ng/mL as significantly associated with pCR (p = 0.036).


Preoperative chemoradiotherapy with oxaliplatin and capecitabine is safe and well tolerated, and offers an interesting ratio of pCR and of tumor downstaging. Presurgical CEA level should be studied as predictors of pCR.


Rectal cancer Neoadjuvant Preoperative MRI CEA nadir 


  1. 1.
    Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer Statistics 2009. CA Cancer J Clin. 2009;59:225–49.PubMedCrossRefGoogle Scholar
  2. 2.
    Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006;24:4620–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72:99–107.PubMedCrossRefGoogle Scholar
  4. 4.
    Theodoropoulos G, Wise WE, Padmanabhan A, et al. T-level downstaging and complete pathologic response after preoperative chemoradiation for advanced rectal cancer result in decreased recurrence and improved disease-free survival. Dis Colon Rectum. 2002;45:895–903.PubMedCrossRefGoogle Scholar
  5. 5.
    Kuo LJ, Liu MC, Jian JJ, et al. Is final TNM staging a predictor for survival in locally advanced rectal cancer after preoperative chemoradiation therapy? Ann Surg Oncol. 2007;14:2766–72.PubMedCrossRefGoogle Scholar
  6. 6.
    Capirci C, Velantini V, Cionini L, et al. Prognostic value of complete response after neoadjuvant therapy in locally advanced rectal cancer: long-term analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys. 2008;72:99–107.PubMedCrossRefGoogle Scholar
  7. 7.
    Frykholm GJ, Glimelius B, Pahlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum. 1993;36:564–72.PubMedCrossRefGoogle Scholar
  8. 8.
    Krishnan S, Janjan NA, Skibber JM, et al. 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.PubMedCrossRefGoogle Scholar
  9. 9.
    Bajetta E, Beretta E, Di Bartolomeo M, et al. Capecitabine chemoradiation for rectal cancer after curative surgery. J Chemother. 2006;18:85–9.PubMedGoogle Scholar
  10. 10.
    Ben-Josef E. Capecitabine and radiotherapy as neoadjuvant treatment for rectal cancer. Am J Clin Oncol. 2007;30:649–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Sawada N, Ishikawa T, Sekiguchi F, et al. X-ray irradiation induces thymidinephosphorylase and enhances the efficacy of capecitabine (Xeloda) in human cancer xenografts. Clin Cancer Res. 1999;5:2948–53.PubMedGoogle Scholar
  12. 12.
    Cividalli A, Ceciarelli F, Livdi E, et al. Radiosensitization by oxaliplatin in a mouse adenocarcinoma: influence of treatment schedule. Int J Radiat Oncol Biol Phys. 2002;52:1092–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Rödel C, Grabenbauer GG, Papadopoulos T, et al. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer. J Clin Oncol. 2003;21:3098–104.PubMedCrossRefGoogle Scholar
  14. 14.
    Carlomagno C, Farella A, Bucci L, D’Armiento FP, Pesce G, Pepe S, Cannella L, Pacelli R, De Stefano A, Solla R, D’Armiento MR, De Placido S. Neo-adjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study. Ann Oncol. 2009;20:906–12.PubMedCrossRefGoogle Scholar
  15. 15.
    Gerard JP, Azria D, Gourgou-Bourgade S, et al. Comparision of two neoadjuvant chemoradiotherapy regiments for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige2. J Clin Oncol. 2010;28:1638–44.PubMedCrossRefGoogle Scholar
  16. 16.
    Aschele C, Pinto C, Cordio S, et al. Preoperative fluorouracil (fu)- based choradiation with and without weekly oxaliplatin in locally advanced rectal cancer: pathologic response analysis of the Studio Terapia Adiuvante reto( STAR)-01 randomized phase III trial (abstract #4008). J Clin Oncol. 2009;27:804s.Google Scholar
  17. 17.
    Park IJ, Choi GS, Lim KH, Kang BM, Jun SH. Serum carcinoembryonic antigen monitoring after curative resection for colorectal cancer: clinical significance of the preoperative level. Ann Surg Oncol. 2009;16:3087–93.PubMedCrossRefGoogle Scholar
  18. 18.
    El-Awady S, Lithy R, Morshed M, et al. Utility of serum preoperative carcinoemberyonic antigen in colorectal cancer patients. Hepatogastroenterology. 2009;56:361–6.PubMedGoogle Scholar
  19. 19.
    Nazato DM, Matos LL, Waisberg DR, Souza JR, Martins LC, Waisberg J. Prognostic value of carcinoembryonic antigen distribution in tumor tissue of colorectal carcinoma. J Arq Gastroenterol. 2009;46:26–31.Google Scholar
  20. 20.
    Perez RO, São Julião GP, Habr-Gama A, et al. The role of carcinoembriogenic antigen in predicting response and survival to neoadjuvant chemoradiotherapy for distal rectal cancer. Dis Colon Rectum. 2009;52:1137–43.PubMedCrossRefGoogle Scholar
  21. 21.
    Hiotis SP, Weber SM, Cohen AM, et al. Assesing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients. J Am Coll Surg. 2002;194:131–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Guillem JG, Chessin DB, Shia J, et al. Clinical examination following preoperative chemoradiation for rectal cancer is not a reliable surrogate end point. J Clin Oncol. 2005;23:3475–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Kahn H, Alexander A, Rakinic J, et al. Preoperative staging of irradiated rectal cancers using digital rectal examination, computed tomography, endorectal ultrasound and magnetic resonance imaging, does not accurately predict T0, N0 pathology. Dis Col Rectum. 1997;40:140–4.CrossRefGoogle Scholar
  24. 24.
    Baglan KL, Frazier RC, Yan D, et al. The dose-volumen relationship of acute small bowel toxicity from concurrent 5-Fu-based chemotherapy and radiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2002;52:176–83.PubMedCrossRefGoogle Scholar
  25. 25.
    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;16:1898–905.PubMedCrossRefGoogle Scholar
  26. 26.
    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 (Suppl): (Abstr 3528).Google Scholar
  27. 27.
    Majem M, Navarro M, Losa F et al. Phase II clinical trial of weekly oxaliplatin with concurrent capecitabine plus preoperative radiotherapy in locally advanced respectable rectal cancer. J Clin Oncol. 2008;26 (Suppl): (Abstr 15013).Google Scholar
  28. 28.
    Fakih MG, Bullard Dun K, Yang GY, et al. A phase II study of weekly intravenous oxaliplatin with oral daily capecitabine and radiotherapy with biological correlates in neoadjuvant treatment of rectal adenocarcinoma. Int J Rad Oncol Biol Phys. 2008;72:650–7.CrossRefGoogle Scholar
  29. 29.
    Alonso V, Lambea J, Salud A et al. Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal carcinoma: a phase II trial. J Clin Oncol. 2007;25 (Suppl): (Abstr 4044).Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Joan Manel Gasent Blesa
    • 1
  • Javier Garde Noguera
    • 1
  • Juan Bautista Laforga Canales
    • 1
  • Vicent Giner Bosch
    • 2
  • Antonio Alberola
    • 1
  • Miguel Soler Tortosa
    • 3
  • Miguel Peris Godoy
    • 4
  • Jose Luis Sanchez
    • 5
  • Mariano Provencio Pulla
    • 6
  • Vicente Alberola Candel
    • 1
  1. 1.Hospital de DéniaDéniaSpain
  2. 2.Departament d’Estadística AplicadaUniversitat Politécnica de ValènciaValenciaSpain
  3. 3.Radiotherapy DepartmentHospital de la RiberaAlziraSpain
  4. 4.Internal Hospital de Dénia, MarinaSaludDéniaSpain
  5. 5.Universidad Católica de ValenciaValenciaSpain
  6. 6.Hospital Universitario Puerta de HierroMadridSpain

Personalised recommendations