Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Effect of Suboptimal Chemotherapy on Preoperative Chemoradiation in Rectal Cancer

직장암 환자의 수술 전 항암화학방사선치료에서 비적정 항암화학요법의 영향

  • Lee, Ji-Hye (Departments of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kang, Hyun-Cheol (Departments of Radiation Oncology, Seoul National University College of Medicine) ;
  • Chie, Eui-Kyu (Departments of Radiation Oncology, Seoul National University College of Medicine) ;
  • Kang, Gyeong-Hoon (Departments of Pathology, Seoul National University College of Medicine) ;
  • Park, Jae-Gahb (Departments of Surgery, Seoul National University College of Medicine) ;
  • Oh, Do-Youn (Internal Medicine, Seoul National University College of Medicine) ;
  • Im, Seock-Ah (Internal Medicine, Seoul National University College of Medicine) ;
  • Kim, Tae-You (Internal Medicine, Seoul National University College of Medicine) ;
  • Bang, Yung-Jue (Internal Medicine, Seoul National University College of Medicine) ;
  • Ha, Sung-Whan (Departments of Radiation Oncology, Seoul National University College of Medicine)
  • 이지혜 (서울대학교 의과대학 방사선종양학교실) ;
  • 강현철 (서울대학교 의과대학 방사선종양학교실) ;
  • 지의규 (서울대학교 의과대학 방사선종양학교실) ;
  • 강경훈 (서울대학교 의과대학 병리학교실) ;
  • 박재갑 (서울대학교 의과대학 외과학교실) ;
  • 오도연 (서울대학교 의과대학 내과학교실) ;
  • 임석아 (서울대학교 의과대학 내과학교실) ;
  • 김태유 (서울대학교 의과대학 내과학교실) ;
  • 방영주 (서울대학교 의과대학 내과학교실) ;
  • 하성환 (서울대학교 의과대학 방사선종양학교실)
  • Received : 2009.03.31
  • Accepted : 2009.06.04
  • Published : 2009.06.30
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Abstract

Purpose: To examine the effect of suboptimal chemotherapy in patients undergoing preoperative chemoradiotherapy for the treatment of rectal cancer. Materials and Methods: The medical records of 43 patients who received preoperative concurrent chemoradiotherapy, followed by radical surgery for the treatment of pathologically proven adenocarcinoma of the rectum from April 2003 to April 2006 were retrospectively reviewed. The delivered radiation dose ranged from 41.4 to 50.4 Gy. The standard group consisted of patients receiving two cycles of a 5-FU bolus injection for three days on the first and fifth week of radiotherapy or twice daily with capecitabine. The standard group included six patients for each regimen. The non-standard group consisted of patients receiving one cycle of 5-FU bolus injection for three days on the first week of radiotherapy. The non-standard group included 31 patients. Radical surgery was performed at a median of 58 days after the end of radiotherapy. A low anterior resection was performed in 36 patients, whereas an abdominoperineal resection was performed in 7 patients. Results: No significant difference was observed between the groups with respect to pathologic responses ranging from grades 3 to 5 (83.3% vs. 67.7%, p=0.456), downstaging (75.0% vs. 67.7%, p=0.727), and a radial resection margin greater than 2 mm (66.7% vs. 83.9%, p=0.237). The sphincter-saving surgery rate in low-lying rectal cancers was lower in the non-standard group (100% vs. 75%, p=0.068). There was no grade 3 or higher toxicity observed in all patients. Conclusion: Considering that the sphincter-saving surgery rate in low-lying rectal cancer was marginally lower for patients treated with non-standard, suboptimal chemotherapy, and that toxicity higher than grade 2 was not observed in the both groups, suboptimal chemotherapy should be avoided in this setting.

목 적: 직장암에서 수술 전 항암화학방사선치료는 수술 후 항암화학방사선치료에 비하여 치료 성적은 비슷하며 독성은 낮아 최근에 많이 시행되고 있다. 본 연구에서는 수술 전 항암화학방사선치료 시 병행한 항암화학요법 중 적정 요법과 적정 이하의 비적정 요법에 따른 치료 결과를 알아보고자 하였다. 대상 및 방법: 2003년 4월부터 2006년 4월까지 수술 전 항암화학방사선치료와 수술을 시행한 환자 중 수술 병리결과 확보가 가능하고 단일 제제 화학요법을 시행한 환자 43명을 대상으로 하였다. 방사선치료는 전 골반에 41.4~50.4 Gy (중앙값, 45 Gy), 종양에 추가조사 0~5.4 Gy (중앙값, 5.4 Gy), 총 41.4~50.4 Gy (중앙값, 50.4 Gy)를 시행하였다. 적정군은 5-fluorouracil (5-FU) 500 mg/$m^2$/day를 방사선치료 첫 3일 동안과 5주 후 3일 동안에 반복 급속 정주 한 6명과 경구 capecitabine을 방사선 치료일에 사용한 6명으로 총 12명이었다. 비적정군은 동일량의 5-FU를 방사선치료 첫 3일에만 급속 정주한 31명이었다. 수술은 방사선치료가 끝난 뒤 40~71일(중앙값, 58일)에 시행하였고 36명은 하전방절제술을, 7명은 복회음절제술을 시행하였다. 결 과: 적정군과 비적정군 사이에, 치료반응 등급 3 이상의 치료반응(83.3% vs. 67.7%, p=0.456), 수술 전과 비교한 수술 후의 병기하강(75.0% vs. 67.7%, p=0.727), 주변절제연 2 mm 초과의 획득(66.7% vs. 83.9%, p=0.237) 등에서 통계적으로 유의하게 차이를 보이지는 않았으나, 병변의 위치가 항문에서 5 cm 이내에 위치한 경우 비적정군에서 괄약근 보존 수술을 시행한 비율이 적정군에 비하여 더 낮은 경향을 보였다(75% vs. 100%, p=0.068). 모든 환자에서 3도 이상의 독성은 관찰되지 않았다. 결 론: 비적정군에서 치료에 수반되는 독성은 낮았으나 모두 2도 이하였고, 항문에서 5 cm 이내에 위치한 직장암의 수술 시 괄약근 보존 수술률이 더 낮은 경향을 보여 적정 화학요법의 병행을 시행하는 것이 바람직하겠다.

Keywords

References

  1. Korea Central Cancer Registry. 2002 Annual Report of the Korea Central Cancer Registry 2003
  2. NIH Consensus Conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1444-1450 https://doi.org/10.1001/jama.264.11.1444
  3. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740 https://doi.org/10.1056/NEJMoa040694
  4. Kim J, Cho M, Song K, et al. Preoperative chemoradiation using oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2002;54:403-408 https://doi.org/10.1016/S0360-3016(02)02856-0
  5. Twelves C, Wong A, Nowacki M, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352:2696-2704 https://doi.org/10.1056/NEJMoa043116
  6. National Comprehensive Cancer Network. Clinical practice guidelines in oncology V.2. 2009: Rectal cancer. http://www.nccn.org/professionals/physician_gls/PDC/rectal.pdf
  7. Chang HJ, Park CK, Kim WH, et al. A standardized pathology report for colorectal cancer. Korean J Path 2006;40:193-203
  8. Gastrointestinal Tumor Study Group. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312:1465-1472 https://doi.org/10.1056/NEJM198506063122301
  9. Pilipshen S, Heilweil M, Quan S, et al. Patterns of pelvic recurrence following definitive resections of rectal cancer. Cancer 1984;53:1354-1362 https://doi.org/10.1002/1097-0142(19840315)53:6<1354::AID-CNCR2820530623>3.0.CO;2-J
  10. Krook J, Moertel C, Gunderson L, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709-715 https://doi.org/10.1056/NEJM199103143241101
  11. Douglass HJ, Moertel C, Mayer R, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med 1986;315:1294-1295 https://doi.org/10.1056/NEJM198611133152014
  12. Kapiteijn E, Marijnen C, Nagtegaal I, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638-646 https://doi.org/10.1056/NEJMoa010580
  13. De Paoli A, Chiara S, Luppi G, et al. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol 2006;17:246-251 https://doi.org/10.1093/annonc/mdj041
  14. Rullier E, Goffre B, Bonnel C, et al. Preoperative radiochemotherapy and sphincter-saving resection for T3 carcinomas of the lower third of the rectum. Ann Surg 2001;234:633-640 https://doi.org/10.1097/00000658-200111000-00008
  15. Rosenberg R, Nekarda H, Zimmermann F, et al. Histopathological response after preoperative radiochemotherapy in rectal carcinoma is associated with improved overall survival. J Surg Oncol 2008;97:8-13 https://doi.org/10.1002/jso.20844
  16. 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 https://doi.org/10.1016/j.ijrobp.2007.12.019
  17. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12:19-23 https://doi.org/10.1007/s003840050072
  18. Mandard A, Dalibard F, Mandard J, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 1994;73:2680-2686 https://doi.org/10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C
  19. Saif M, Hashmi S, Zelterman D, et al. Capecitabine vs continuous infusion 5-FU in neoadjuvant treatment of rectal cancer. A retrospective review. Int J Colorectal Dis 2008;23: 139-145 https://doi.org/10.1007/s00384-007-0382-z
  20. de Bruin A, Nuyttens J, Ferenschild F, et al. Preoperative chemoradiation with capecitabine in locally advanced rectal cancer. Neth J Med 2008;66:71-76
  21. Das P, Skibber J, Rodriguez-Bigas M, et al. Predictors of tumor response and downstaging in patients who receive preoperative chemoradiation for rectal cancer. Cancer 2007; 109:1750-1755 https://doi.org/10.1002/cncr.22625
  22. O'Connell M, Martenson J, Wieand H, et al. Improving adjuvant therapy for rectal cancer by combining protractedinfusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994;331:502-507 https://doi.org/10.1056/NEJM199408253310803
  23. Smalley S, Benedetti J, Williamson S, et al. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 2006;24:3542-3547 https://doi.org/10.1200/JCO.2005.04.9544
  24. Scheithauer W, McKendrick J, Begbie S, et al. Oral capecitabine as an alternative to i.v. 5-fluorouracil-based adjuvant therapy for colon cancer: safety results of a randomized, phase III trial. Ann Oncol 2003;14:1735-1743 https://doi.org/10.1093/annonc/mdg500
  25. Bazarbashi S, El-Bassiouni M, Abdelsalam M, et al. A modern regimen of pre-operative concurrent chemo-radiation therapy in locally advanced rectal cancer. J Surg Oncol 2008; 98:167-174 https://doi.org/10.1002/jso.21097
  26. Di Costanzo F, Ravasio R, Sobrero A, et al. Capecitabine versus bolus fluorouracil plus leucovorin (folinic acid) as adjuvant chemotherapy for patients with Dukes' C colon cancer: economic evaluation in an Italian NHS setting. Clin Drug Investig 2008;28:645-655 https://doi.org/10.2165/00044011-200828100-00005
  27. Dupuis O, Vie B, Lledo G, et al. Preoperative treatment combining capecitabine with radiation therapy in rectal cancer: a GERCOR Phase II Study. Oncology 2007;73:169-176 https://doi.org/10.1159/000127383
  28. Aschele C, Friso M, Pucciarelli S, et al. A phase I-II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 2005;16:1140-1146 https://doi.org/10.1093/annonc/mdi212
  29. Mehta V, Cho C, Ford J, et al. Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasoundstaged T3 rectal cancer. Int J Radiat Oncol Biol Phys 2003;55: 132-137 https://doi.org/10.1016/S0360-3016(02)03863-4
  30. Glynne-Jones R, Sebag-Montefiore D, Maughan T, et al. A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOX-RT) in patients with locally advanced rectal cancer. Ann Oncol 2006;17:50-56 https://doi.org/10.1093/annonc/mdj031
  31. Choi SG, Bae HS. Results of preoperative concurrent chemoradiotherapy for locally advanced rectal cancer. J Korean Soc Ther Radiol Oncol 2007;25:34-42
  32. Luna-Pérez P, Rodríguez-Ramírez S, Rodriguez-Coria D, et al. Preoperative chemoradiation therapy and anal sphincter preservation with locally advanced rectal adenocarcinoma. World J Surg 2001;25:1006-1011 https://doi.org/10.1007/s00268-001-0071-y
  33. Grann A, Feng C, Wong D, et al. Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2001;49:987-995 https://doi.org/10.1016/S0360-3016(00)01529-7