Concurrent Chemoradiation with Weekly Paclitaxel in Locally Advanced Non-small Cell Lung Cancer

국소진행성 비소세포폐암에서 Paclitaxel 매주투여 및 방사선치료 동시요법

  • Bae, Kang Woo (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Song, Tak Ho (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Yang, Joo Yeon (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Kim, Yun Seup (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Park, Jae Seok (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Jee, Young Koo (Department of Internal Medicine, Dankook University College of Medicine) ;
  • Lee, Kye Young (Department of Internal Medicine, Dankook University College of Medicine)
  • 배강우 (단국대학교 의과대학 내과학교실) ;
  • 송탁호 (단국대학교 의과대학 내과학교실) ;
  • 양주연 (단국대학교 의과대학 내과학교실) ;
  • 김윤섭 (단국대학교 의과대학 내과학교실) ;
  • 박재석 (단국대학교 의과대학 내과학교실) ;
  • 지영구 (단국대학교 의과대학 내과학교실) ;
  • 이계영 (단국대학교 의과대학 내과학교실)
  • Received : 2004.06.15
  • Accepted : 2004.07.15
  • Published : 2004.10.30

Abstract

Background : Paclitaxel is highly beneficial anticancer drug for the treatment of non-small cell lung cancer and has shown remarkable radiosensitizing effect in vitro. We evaluated whether concurrent chemoradiation therapy with weekly paclitaxel (60 $mg/m^2$) could be tolerated and effective in the treatment of locally advanced non-small cell lung cancer (NSCLC). Methods : Twenty-two stage III (IIIA:6, IIIB:16) NSCLC patients were treated with weekly administration of paclitaxel (60 $mg/m^2$) on days 1, 8, 15, 22, 29, and 36 in addition to concurrent radiation therapy of 54 Gy. After the initial phase of concurrent chemoradiation, patients received additional two cycles of consolidation chemotherapy with paclitaxel (175 $mg/m^2$)/cisplatin (75 $mg/m^2$) or paclitaxel (175 $mg/m^2$)/carboplatin (6AUC) every 3 weeks. Results : Overall response rate was 81.8% (18/22) with 9.1% (2/22) of complete response and 72.7% (16/22) of partial response rate. Two patients (9.1%) died of chemoradiation-induced pneumonitis after completion of therapy. In total, grade 3 toxicities included pneumonitis (22.7%), esophagitis (22.7%), neuropathy (13.6%), and neutropenia (13.6%). The median survival time was 15 months and 2-year overall survival were 31.8%. Conclusion : Concurrent chemoradiation therapy with weekly paclitaxel in locally advanced NSCLC showed good local response, but survival rate was not completely satisfactory due to potentially fatal chemoradiation-induced pneumonitis.

연구배경 : 최근 항암화학요법과 방사선요법의 병용치료는 국소진행성 비소세포폐암 치료에 있어서 표준치료방법으로 자리잡고 있으며 동시요법이 순차적요법에 비해 치료반응율에 있어서 우수하다고 알려져 있다. 본 연구는 비소세포폐암 치료에 있어서 우수한 효과를 보이고 방사선감작 효과가 있다고 알려진 paclitaxel (60 $mg/m^2$) 매주투여와 동시 방사선요법의 III병기 비소세포폐암 환자에서의 치료효과와 독성을 조사하기 위하여 시행하였다. 방 법 : III병기 비소세포폐암 환자 22명 (IIIA:6, IIIB:16)을 대상으로 paclitaxel (60 $mg/m^2$)을 제 1, 8, 15, 22, 29, and 36일째에 매주 투여하고 동시에 54 Gy의 방사선 치료를 시행하였다. 초기 동시치료를 종료하고 paclitaxel (175 $mg/m^2$)/cisplatin (75 $mg/m^2$) 혹은 paclitaxel (175 $mg/m^2$)/carboplatin (6AUC) regimen 으로 보강화학요법을 3주 간격으로 2주기 시행하였다. 결 과 : 전반적 치료반응율은 81.8% (18/22)로서 완전관해가 9.1% (2/22), 부분관해가 72.7% (16/22)의 결과를 보였다. 두명의 (9.1%) 환자가 치료종료 후 방사선폐장염의 합병증으로 사망하였다. 3도 이상의 독성 반응은 방사선폐장염 (22.7%), 식도염 (22.7%), 신경병증 (13.6%), 및 백혈구감소증 (13.6%)의 결과를 나타내었다. 중앙생존기간은 15개월이었고 1년 및 2년 생존율은 각각 63.6%와 31.8%였다. 결 론 : 국소진행성 비소세포폐암 환자에서 paclitaxel 매주 투여에 의한 동시 방사선요법은 우수한 종양반응율을 나타내지만 치명적인 방사선폐장염의 발생 위험이 있으므로 향후 보완연구가 필요할 것으로 사료된다.

Keywords

References

  1. Petrovich Z, Stanley K, Cox JD, Paig C. Radiotherapy in the management of locally advanced lung cancer of all cell types: final report of randomized trial. Cancer 1981;48:1335-40
  2. Cox JD, Pajak TF, Herskovic A, Urtasun R, Podolsky WJ, Seydel HG. Five-year survival after hyperfractionated radiation therapy for non-small-cell carcinoma of the lung (NSCCL): results of RTOG protocol 81-08. Am J Clin Oncol 1991;14:280-4
  3. Dillman RO, Seagren SL, Propert KJ, Guerra J, Eaton WL, Perry MC et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer. N Engl J Med 1990;323:940-5
  4. Sause WT, Scott C, Taylor S, Johnson D, Livingston R, Komaki R, et al. Radiation Therapy Oncology Group (RTOG) 88-08 and Eastern CooperativeOncology Group (ECOG) 4588: preliminary results of a phase III trial in regionally advanced, unresectable non-small-cell lung cancer. J Natl Cancer Inst 1995;87:198-205
  5. Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999;17:2692-9
  6. Curran WJ, Scott C, Langer C. Phase III comparison of sequential vs. concurrent chemoradiation for patients with unrescted stage III non-small cell lung cancer (NSCLC): initial report of Radiation Therapy Oncology Group (RTOG) 9410. Proc Am Soc Clin Oncol 2000;10:1891
  7. Greco FA. Paclitaxel-based combination chemotherapy in advanced non-small cell lung cancer. Lung Cancer 2001;34(Suppl 4):S53-6
  8. Milas L, Hunter NR, Mason KA, Milross CG, Saito Y, Peters LJ. Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel.Cancer Res 1995;55:3564-8
  9. Milas L, Hunter NR, Mason KA, Kurdoglu B, Peters LJ. Enhancement of tumor radioresponse of a murine mammary carcinoma by paclitaxel. Cancer Res1994;54:3506-10
  10. Caffo O. Radiosensitization with chemotherapeutic agents. Lung Cancer 2001;34 (Suppl 4):S81-90
  11. Zanelli GD, Quaia M, Robieux I, Bujor L, Santarosa M, Favaro D, et al. Paclitaxel as a radiosensitizer: a proposed schedule of administration based on in vitrodata and pharmacokinetic calculations. Eur J Cancer 1997;33:486-92
  12. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer 1981;47: 207-14
  13. Johnson DH. Locally advanced, unresectable nonsmall cell lung cancer: new treatment strategies. Chest 2000; 117(4 Suppl 1):123S-126S
  14. Belani CP. Combined modality therapy for unresectable stage III non-small cell lung cancer: new chemotherapy combinations. Chest 2000; 117 (4 Suppl 1):127S-132S
  15. Jassem J. Combined modality treatment with chemotherapy and radiation in locally advanced non-small cell lung cancer. Lung Cancer 2001;34(Suppl 2):S181-3
  16. Dillman RO, Herndon J, Seagren SL, Eaton WL Jr, Green MR. Improved survival in stage III nonsmall-cell lung cancer: seven-year follow-up of cancer and leukemia group B [CALGB] 8433 trial. J Natl Cancer Inst 1996; 88:1210–5
  17. Sause W, Kolesar P, Taylor S IV, Johnson D, Livingston R, Komaki R, et al. Final results of phase III trial in regionally advanced unresectable nonsmallcell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000;117:358-64
  18. Le Chevalier T, Arriagada R, Tarayre M, Lacombe-Terrier MJ, Laplanche A, Quoix E, et al. Significant effect of adjuvant chemotherapy on survival in locallyadvanced non-small-cell lung carcinoma. J Natl Cancer Inst 1992;84:58
  19. Gaspar LE. Optimizing chemoradiation therapy approaches to unresectable stage III non-small cell lung cnacer. Curr Opin Oncol 2001;13:110-5
  20. Movsas B, Scott C, Curran WJ. A quality-adjusted time without symptoms or toxicity (QTWIST). Analysis of Radiation Therapy Oncology Group [RTOG] 9410. Proc Am Soc Clin Oncol 2001;20:313a.(Abstract)
  21. Jassem J. Combined chemotherapy and radiation in locally advanced non-small cell lung cancer. Lancet Oncol 2001;2:335–42
  22. Vokes EE, Herndon JE 2nd, Crawford J, Leopold KA, Perry MC, Miller AA, et al. Randomized phase II study of cisplatin with gemcitabine or paclitaxel orvinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: cancer and leukemia group B study 9431. J Clin Oncol 2002;20:4191-8
  23. Choy H, Akerley W, Safran H, Clark J, Rege V, Papa A, et al. Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advancednon-small cell lung cancer. J Clin Oncol 1994;12:2682-6
  24. Rowisky EK, Donehower RC. Paclitaxel (taxol). N Engl J Med 1995;332:1004-14
  25. Kirkbride P, Gelmon K, Eisenhauer E. Pacltaxel and concurrent radiotherapy in locally advanced non-small cell lung cancer: the Canadian experience. Semin Radiat Oncol 1999;9:102-7