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Preoperative Radiotherapy Combined with Capecitabine Chemotherapy in Chinese Patients with Locally Advanced Rectal Cancer

  • Original Article
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Journal of Gastrointestinal Surgery

Abstract

Background

This phase II study is performed to evaluate the efficacy and safety of capecitabine combined with preoperative radiotherapy (RT) in Chinese patients with locally advanced rectal cancer (LARC).

Methods

Between February 2007 and December 2008, 62 patients with LARC were treated with capecitabine (825 mg/m2, twice daily) and concurrent RT (50.4 Gy/28 fractions). Patients underwent surgery after 6–8 weeks of combined therapy, followed by 4 cycles of adjuvant capecitabine (1,250 mg/m2, twice daily on days 1–14, every 3 weeks). The primary endpoint was the rate of pathologic complete response (pCR).

Results

Fifty-eight patients (93.5%) completed the preoperative chemoradiation course as initially planned. The most severe hematologic adverse event was leucopenia, which occurred with grade 2 intensity in 12 (19.7%) patients and grade 3 in 2 (3.3%) patients. Grade 3 diarrhea and hand–foot syndrome (HFS) were observed in one (1.6%) and two (3.3%) patients, respectively. However, no grade 4 toxicity was observed. There were no treatment-related deaths during this study. Of the 59 patients treated with surgery, all had radial margins (R0 resections). Among the 29 patients with the primary tumor ≤5 cm from the anal verge, 18 (62.1%) underwent sphincter-preserving surgical resections. pCR was found in eight patients (13.6%). The pathologic stage was lower than the initial clinical stage in 57.6% (34/59), 63.4% (26/41), and 81.4% (48/59) of the resected tumors for the primary tumor (T), lymph node (N), and combined TN categories, respectively. The estimate of disease-free survival and overall survival at 24 months were 80.6% (95% CI, 70.8–90.4%) and 92.5% (95% CI, 85.9–99.1%), respectively.

Conclusion

Preoperative chemoradiotherapy with capecitabine and RT appears to be a safe, well-tolerated, and effective neoadjuvant treatment modality for LARC.

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References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71–96.

    Article  PubMed  Google Scholar 

  2. Bosset JF, Calais G, Daban A, Berger C, Radosevic-Jelic L, Maingon P, et al. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer 2004;40:219–224.

    Article  PubMed  CAS  Google Scholar 

  3. 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;24:4620–4625.

    Article  PubMed  Google Scholar 

  4. Rouanet P, Rivoire M, Lelong B, Rullier E, Dravet F, Mineur L, et al.: Sphincter preserving surgery after preoperative treatment for ultra-low rectal carcinoma. A French multicenter prospective trial: GRECCAR 1. 2006 ASCO Annual Meeting Proceedings. J Clin Oncol 24:18S, 2006 (abstr 3527).

    Google Scholar 

  5. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 2006;93:1215–1223.

    Article  PubMed  CAS  Google Scholar 

  6. Wagner TD, Fakih MG, Yang GY. Management of stage II/III rectal cancer. J Gastrointest Oncol 2010; 1: 112–119.

    CAS  Google Scholar 

  7. Vonk DT, Hazard LJ. Do all locally advanced rectal cancers require radiation? A review of literature in the modern era. J Gastrointest Oncol 2010; 1: 45–54.

    Google Scholar 

  8. Schüller J, Cassidy J, Dumont E, Roos B, Durston S, Banken L, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol 2000;45:291–297.

    Article  PubMed  Google Scholar 

  9. 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;5:2948–2953.

    PubMed  CAS  Google Scholar 

  10. Trotti A, Byhardt R, Stetz J, Gwede C, Corn B, Fu K, et al. Common toxicity criteria: version 2.0. An improved reference for grading the acute effects of cancer treatment: impact on radiotherapy. Int J Radiat Oncol Biol Phys 2000;47:13–47.

    Article  PubMed  CAS  Google Scholar 

  11. Blum JL, Jones SE, Buzdar AU, LoRusso PM, Kuter I, Vogel C, et al. Multicenter phase II study of capecitabine in paclitaxel-refractory metastatic breast cancer. J Clin Oncol 1999;17:485–493.

    PubMed  CAS  Google Scholar 

  12. Hyams DM, Mamounas EP, Petrelli N, Rockette H, Jones J, Wieand HS, et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03. Dis Colon Rectum 1997;40:131–139.

    Article  PubMed  CAS  Google Scholar 

  13. Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004; 21;351:1731–1740.

    Article  Google Scholar 

  14. Kim JS, Kim JS, Cho MJ, Song KS, Yoon WH. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002;54:403–408.

    Article  PubMed  CAS  Google Scholar 

  15. Kocakova I, Spelda S, Svoboda M, Vyzula R, Kocak I, Brancikova D, et al. Combined therapy of locally advanced rectal adenocarcinoma with capecitabine and concurrent radiotherapy [Abstract]. Proc Am Soc Clin Oncol 2003;22:322.

    Google Scholar 

  16. Dunst J, Reese T, Debus J, Hoelscher W, Budach V, Rudat J, et al. Phase II study of preoperative chemoradiation with capecitabine in rectal cancer [Abstract]. Proc Am Soc Clin Oncol 2004;23:260.

    Google Scholar 

  17. Wong SJ, Sadasiwan C, Erickson B, Ota D, Mulkerin D, Thomas J, et al. A phase II trial of pre-operative capecitabine and concurrent radiation for locally advanced rectal cancer [Abstract]. Proc Am Soc Clin Oncol 2004;23:312.

    Google Scholar 

  18. De Paoli A, Chiara S, Luppi G, Friso ML, Beretta G, Delprete S, et al. A phase II study of capecitabine (CAP) and pre-operative radiation therapy (RT) in resectable, locally advanced rectal cancer (LARC) [Abstract]. Proc Am Soc Clin Oncol 2004;23:255.

    Google Scholar 

  19. Dupuis O, Vie B, Lledo G, Hennequin C, Noirclerc M, Bennamoun M, et al. Capecitabine (X) chemoradiation (CRT) in the perioperative treatment of patients (pts) with rectal adenocarcinomas: A phase II GERCOR trial [Abstract]. Proc Am Soc Clin Oncol 2004;23:255.

    Google Scholar 

  20. Chen YJ, Chung V. Challenges toward personalized treatment of localized colorectal cancer. J Gastrointest Oncol 2010; 1: 74–75.

    Google Scholar 

  21. Kim JC, Kim TW, Kim JH, Yu CS, Kim HC, Chang HM, et al. Preoperative concurrent radiotherapy with capcitabine before total mesorectal excision in locally advanced rectal cancer. Int J Radiat Oncol Biol phys 2005; 63:346–353.

    Article  PubMed  CAS  Google Scholar 

  22. De Paoli A, Chiara S, Luppi G, Friso ML, Beretta GD, Del Prete S, et al. Capcitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol 2006; 17:246–251.

    Article  PubMed  Google Scholar 

  23. Krishnan S, Janjan NA, Skibber JM, Rodriguez-Bigas MA, Wolff RA, Das P, 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;66:762–771.

    Article  PubMed  CAS  Google Scholar 

  24. Craven I, Crellin A, Cooper R, Melcher A, Byrne P, Sebag-Montefiore D. Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer. Br J Cancer 2007;97:1333–1337.

    Article  PubMed  CAS  Google Scholar 

  25. 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.

    PubMed  CAS  Google Scholar 

  26. Elwanis MA, Maximous DW, Elsayed MI, Mikhail NN. Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial. World J Surg Oncol 2009;7:52.

    Article  PubMed  Google Scholar 

  27. De Bruin AF, Nuyttens JJ, Ferenschild FT, Planting AS, Verhoef C, De Wilt JH. Preoperative chemoradiation with capecitabine in locally advanced rectal cancer. Neth J Med 2008; 66:71–76.

    PubMed  Google Scholar 

  28. Dunst J, Debuse J, Rudat V, Wulf J, Budach W, Hoelscher T, et al. Neoadjuvant capcitabine combined with standard radiotherapy in patients with locally advanced rectal cancer: Mature results of a phase II trial. Strahlenther Onkol 2008; 184:450–456.

    Article  PubMed  Google Scholar 

  29. 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; 73:169–176.

    Article  PubMed  Google Scholar 

  30. Korkolis DP, Boskos CS, Plataniotis GD, Gontikakis E, Karaitianos IJ, Avgerinos K, et al. Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer. Anticancer Res 2007;27:541–545.

    PubMed  CAS  Google Scholar 

  31. Cancer and Leukemia Group B 89901, Ryan DP, Niedzwiecki D, Hollis D, Mediema BE, Wadler S, Tepper JE, et al. Phase I/II study of preoperative oxaliplatin, fluorouracil, and external-beam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901. J Clin Oncol 2006;24:2557–2562.

    Google Scholar 

  32. Sastre J, Custodio A, Sanchez JC, Ortega L, Rodriguez L, Puente J, et al. Risk-adapted adjuvant chemotherapy after concomitant fluoropyrimidine-radiotherapy neoadjuvant treatment for patients with resectable cT3-4 or N + rectal cancer. Anticancer Drugs 2011;22:185–190.

    Article  PubMed  CAS  Google Scholar 

  33. Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM; on behalf of the Timing of Rectal Cancer Response to Chemoradiation Consortium. Optimal Timing of Surgery After Chemoradiation for Advanced Rectal Cancer: Preliminary Results of a Multicenter, Nonrandomized Phase II Prospective Trial. Ann Surg 2011;254:97–102.

    Google Scholar 

  34. 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 2010 Oct 13. doi:10.1016/j.ijrobp.2010.08.005.

  35. Chen ET, Mohiuddin M, Brodovsky H, Fishbein G, Marks G. Downstaging of advanced rectal cancer following combined preoperative chemotherapy and high dose radiation. Int J Radiat Oncol Biol Phys 1994; 30:169–175.

    PubMed  CAS  Google Scholar 

  36. Janjan NA, Khoo VS, Abbruzzese J, Pazdur R, Dubrow R, Cleary KR, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44:1027–1038.

    Article  PubMed  CAS  Google Scholar 

  37. Guillem JG, Chessin DB, Cohen AM, Shia J, Mazumdar M, Enker W, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005;241:829–836.

    Article  PubMed  Google Scholar 

  38. Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997;15:110–115.

    PubMed  CAS  Google Scholar 

  39. Francois Y, Nemoz CJ, Baulieux J, Vignal J, Grandjean JP, Partensky C, et al. Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial. J Clin Oncol 1999;17:2396.

    PubMed  CAS  Google Scholar 

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Funding

The research was supported in part by the Social Development Foundation of Science Technology Bureau of Wujin District, Changzhou, People's Republic of China (no. ws2009010).

Conflict of Interest

None declared.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Wujin People’s Hospital, Jiangsu University, No. 2, North Yongning Rd, Changzhou, 213002, People’s Republic of China

    Jianhua Jin, Fang Wang, Wenbin Lu, Xianwen Li, Hua Zhang & Jianzhong Deng

  2. Department of Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China

    Hua Meng

  3. Department of Oncology, 163rd Hospital of People’s Liberation Army (PLA), Changsa, People’s Republic of China

    Guanghua Zhou

  4. Department of Gastrointestinal Surgery, Wujin People’s Hospital, Jiangsu University, Changzhou, People’s Republic of China

    Xuezhong Xu

  5. Department of Pathology, Wujin People’s Hospital, Jiangsu University, Changzhou, People’s Republic of China

    Zhixin Xue

  6. Department of Radiation Therapy, Changzhou Cancer Hospital, Soochow University, Changzhou, People’s Republic of China

    Xiyuan Xu

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  1. Jianhua Jin
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  10. Hua Zhang
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Correspondence to Jianhua Jin.

Additional information

Jianhua Jin, Hua Meng, and Guanghua Zhou made equal contribution to this study.

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Jin, J., Meng, H., Zhou, G. et al. Preoperative Radiotherapy Combined with Capecitabine Chemotherapy in Chinese Patients with Locally Advanced Rectal Cancer. J Gastrointest Surg 15, 1858–1865 (2011). https://doi.org/10.1007/s11605-011-1637-0

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  • DOI: https://doi.org/10.1007/s11605-011-1637-0

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