Impact of Postoperative Oral Administration of UFT for Completely Resected pT2N0 Non-Small Cell Lung Cancer

완전 절제된 비소세포폐암 병기 IB (pT2N0) 환자에서 수술 후 UFT의 효과

  • Lee, Jin-Gu (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Park, In-Kyu (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Kim, Dae-Joon (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Kim, Kil-Dong (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Cho, Sang-Ho (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine) ;
  • Chung, Kyung-Young (Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine)
  • 이진구 (연세대학교 의과대학 흉부외과학교실) ;
  • 박인규 (연세대학교 의과대학 흉부외과학교실) ;
  • 김대준 (연세대학교 의과대학 흉부외과학교실) ;
  • 김길동 (연세대학교 의과대학 흉부외과학교실) ;
  • 조상호 (연세대학교 의과대학 흉부외과학교실) ;
  • 정경영 (연세대학교 의과대학 흉부외과학교실)
  • Published : 2007.06.05

Abstract

Background: Recent studies have suggested that UFT may be an effective adjuvant therapy for completely resected IB (pT2N0) non-small cell lung cancer (NSCLC). We designed this study to clarify the feasibility of performing adjuvant chemotherapy with UFT for completely resected IB nor-small cell lung cancer, Material and Method: We randomly assigned patients suffering with completely resected IB non-small cell lung cancer to receive either UFT 3g for 2 year or they received no treatment. All patients had to be followed until death or the cut-off date (December 31 2006). Result: From June 2002 through December 2004, 64 patients were enrolled. Thirty five patients were assigned to receive UFT (the UFT group) and 29 patients were assigned to observation (the control group). A follow-up surrey on the 3 year survival rate was successfully completed for all the patients. The median follow-up time for all the patients was 32.8 months. In the UFT group, the median time of administration was 98 weeks (range: $2{\sim}129$ weeks). The rate of compliance was 88.2% at 6 months, 87.5% at 12 months, 80.6% at 18 month and 66.7% at 24 months. Seven recurrences (24.1%) occurred in the control group and six (17.1%) occurred in the UFT group (p=0,489). The three-year disease free survival rate was 71.3% for the control group and 82.0% for the UFT group (p=0.331). On the subgroup analysis, the three-year disease free survival rate for the patients with adenocacinoma was 45.0% for the control group and 75.2% for the UFT group (p=0.121). The three-year disease free survival rate for the patients with non-adenocarcinoma was 88.1% for the control group and 88.9% for the UFT group (p=0.964), Conclusion: Postoperative oral administration of UFT was well-tolerated. Adjuvant chemotherapy with UFT for completely resected pT2N0 adenocarcinoma of the lung could be expected to improve the disease free survival, but this failed to achieve statistical significance. A prospective randomized study for a large number of patients will be necessary.

배경: 최근의 연구들에서 완전 절제된 병기 IB (pT2N0) 비소세포폐암 환자에서 수술 후 보조 항암요법으로 UFT의 효과에 대해 보고되고 있다. 이에 본 저자들은 완전 절제된 병기 IB 비소세포폐암에서 보조 항암요법으로 UFT의 가능성을 확인하고자 본 연구를 진행하였다. 대상 및 방법: 완전 절제된 병기 IB 비소세포페암 환자를 대상으로 무작위로 수술 후 2년간 3g의 UFT 사용군(UFT군)과 수술만 시행한 군(비교군)으로 나누었다. 모든 환자는 사망 또는 관찰 완료시점(2006년 12월 31일)까지 추적하였다. 결과: 2002년 6월부터 2004년 12월까지 모두 64명의 환자가 포함되었고 UFT 사용군이 35명, 비교군이 29명이었다 모든 환자의 추적 기간의 중앙값은 32.8개월이었으며 모든 환자에 있어서 관찰종료시점까지 추적이 가능하였다. UFT군에서 UFT 투여된 기간의 중앙값은 98주(범위: $2{\sim}129$주)였다. 약물의 순응도는 6개월에 88.2%, 12개월에 87.5%, 18개월에 80.6%, 24개월에 66.7%였다. 추적중 비교군에서 7명(24.1%), UFT군에서 6명(17.1%)의 환자가 재발하였다(p=0.489). 3년 무병생존율은 비교군에서 71.3%, UFT군에서 82.0%였다(p=0.331). 비소세포폐암 중 선암만을 대상으로 비교 시 3년 무병생존율이 비교군에서 45.0%, UFT군에서 75.2%였고(p=0.121) 비-선암을 대상을 했을 때 3년 무병생존율이 비교군에서 88.1%, UFT군에서 88.9%였다(p=0.964). 결론: 병기 IB 비소세포폐암에서 수술 후 경구 UFT의 보조항암요법은 안전하게 장기간 투여할 수 있었고 비록 통계학적인 의의를 얻지는 못했으나 완전 절제된 IB기 비소세포폐암 환자에서 수술 후 UFT보조항암요법은 생존율의 향상에 기여할 것으로 기대되며 특히 선암 환자에 있어서 생존율의 향상을 기대할 수 있을 것으로 판단된다. 향후 많은 환자를 대상으로 하는 선향적 무작위연구가 필요하리라 여겨진다.

Keywords

References

  1. Jones D, Detterbeck F. Surgery for stage I non-small cell lung cancer. In: Detterbaeck F, Rivera M, Socinski M, Rosenman J. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia: W.B. Saunders Company. 2001;177-90
  2. Martini N, Bains M, Burt M, et al. Incidence of local recurrence and second primoary tumors in resected stage I lung cancer. J Thorac Cardiovasc Surg 1995;109:120-9 https://doi.org/10.1016/S0022-5223(95)70427-2
  3. Martini N, Burt M, Bains M, McCormack P, Rusch V, Ginsberg R. Surgical treatment of non-small cell lung cancer by stage. Semin Surg Oncol 1990;6:248-54 https://doi.org/10.1002/ssu.2980060505
  4. Ihde D, Ball D, Arriagada R, et al. Postoperative adjuvant therapy for non-small cell lung cancer: a consensus report. Lung Cancer 1994;11(Suppl):15-7
  5. Ohta M, Tsuchiya R, Shimoyama M, et al. The Japan Clinical Oncology Group. Adjuvant chemotherapy for completely resected stage III non-small cell lung cancer. J Thorac Cardiovasc Surg 1993;106:703-8
  6. Socinski M, Detterbeck F, Rosenman J. Adjuvant therapy of resected non-small cell lung cancer. In: Detterbaeck F, Rivera M, Socinski M, Rosenman J. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. Philadelphia:W.B. Saunders Company. 2001:206-19
  7. Ichinose Y. A randomized phase III trial of adjuvant treatment for resected non-small cell lung cancer in Japan. Cancer Chemother Pharmacol 2006;58(Suppl):43-8 https://doi.org/10.1007/s00280-006-0315-5
  8. Park I, Chung K, Kim K, Kim D. Prognostic factors for disease-free survival in pT2N0 non-small cell lung cancer. Asian Cardiovasc Thorac Ann 2006;14:139-44 https://doi.org/10.1177/021849230601400212
  9. Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Publish Date: August 9, 2006. Available at: http://ctep.cancer.gov/forms/CTCAEv3.pdf. Accessed January 25, 2007
  10. Feld R, Rubinstein L, Weisenberger T. The Lung Cancer Study Group. Site of recurrence stage I non-small cell lung cancer: a guide for future study. J Clin Oncol 1984; 2:1352-8 https://doi.org/10.1200/JCO.1984.2.12.1352
  11. Ohgami A, Mitudomi T, Sugio K, Oyama T, Yasumoto K. Micrometastatic tumor cells in the bone marrow of patients with non-small cell lung cancer. Ann Thorac Surg 1997; 64:363-7 https://doi.org/10.1016/S0003-4975(97)00543-2
  12. Winton TL, Livingstan R, Johnson D, et al. A prospective randomized trial of adjuvant vinorelbine (VNR) and cisplatin (CIS) in completely resected stage Ib and II non-small cell lung cancer (NSCLC) Intergroup JBR 10. J Clin Oncol 2004;22(Suppl):621s(abstr 7018)
  13. Strauss GM, Hernden J, Maddaus MA, et al. Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage Ib non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) protocol 9633. J Clin Oncol 2004;22(Suppl): 621s(abstr 7019)
  14. Kim K, Chung K, Hong K, Kim D. The surgical results of stage I lung cancer. Korean J Thorac Cardiovasc Surg 1998;31:982-7
  15. Pinedo H, Peter E. Fluorouracil: biochemistry and pharmacology. J Clin Oncol 1988;6:1653-64 https://doi.org/10.1200/JCO.1988.6.10.1653
  16. Keicho N, Sajio N, Shinkai T, et al. Phase II study of UFT in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol 1986;16:143-6 https://doi.org/10.1093/oxfordjournals.jjco.a039130
  17. Endo C, Saito Y, Iwanami H, et al. A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery. Lung Cancer 2003;40:181-6 https://doi.org/10.1016/S0169-5002(03)00032-1
  18. Kato H, Ichinose Y, Ohta M, et al. A randomized trail of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004;350:1713-21 https://doi.org/10.1056/NEJMoa032792
  19. Wada H, Hitomi S, Teramatsu T. Adjuvant chemotherapy after complete resection in non-small cell lung cancer. West Japan study group for lung cancer surgery. J Clin Oncol 1996;14:1048-54 https://doi.org/10.1200/JCO.1996.14.4.1048
  20. Hamada C, Tanaka F, Ohta M, et al. Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non-small-cell lung cancer. J Clin Oncol 2005;23:4999-5006 https://doi.org/10.1200/JCO.2005.09.017