Phase II Study of Irinotecan Plus Cisplatin as First Line therapy in Extensive Small-Cell Lung Cancer

확장기 소세포폐암에서 1차 치료로서 Irinotecan + Cisplatin 복합요법의 임상적 결과

  • Hwang, Ki Eun (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Kim, So Young (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Jung, Jong Hoon (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Park, Seong Hoon (Department of Radiology, College of Medicine, Wonkwang University) ;
  • Park, Jung Hyun (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Kim, Hwi Jung (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Kim, Hak Ryul (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Yang, Sei Hoon (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Jeong, Eun Taik (Department of Internal Medicine, College of Medicine, Wonkwang University)
  • 황기은 (원광대학교 의과대학 내과학교실) ;
  • 김소영 (원광대학교 의과대학 내과학교실) ;
  • 정종훈 (원광대학교 의과대학 내과학교실) ;
  • 박성훈 (원광대학교 의과대학 진단방사선과학교실) ;
  • 박정현 (원광대학교 의과대학 내과학교실) ;
  • 김휘정 (원광대학교 의과대학 내과학교실) ;
  • 김학렬 (원광대학교 의과대학 내과학교실) ;
  • 양세훈 (원광대학교 의과대학 내과학교실) ;
  • 정은택 (원광대학교 의과대학 내과학교실)
  • Received : 2006.05.25
  • Accepted : 2006.07.12
  • Published : 2006.08.30

Abstract

Background: Irinotecan (topoisomerase I inhibitor) is effective as a monotherapy against small-cell lung cancer(SCLC). Cisplatin is also an important drug against SCLC. A phase II study of irinotecan combined with cisplatin was carried out to evaluate the efficacy and toxicity of this combined regimen as a first line treatment in patients with extensive SCLC. Methods: Thirty-nine patients with previously untreated extensive SCLC were enrolled in this study. Irinotecan $60mg/m^2$ was administered intravenously on days 1, 8 and 15, and in combination with cisplatin $60mg/m^2$ on day 1 and every 28 days thereafter. Four cycles of chemotherapy were given to the patients. Results: The overall response rate was 77% with a complete response (CR) rate of 8%. The median survival time, 1- and 2-year survival rate were 14.8 months, 60.9% and 27.6%, respectively. The median progression free survival time, 6-and 12-month progression free survival rate were 8.4 months, 75% and 18.8%, respectively. The WHO grade 3 or more toxicity encountered were leukopenia (23%), diarrhea (26%). Two patients changed their chemotherapeutic regimen and one patient died from severe diarrhea. Conclusion: The combination of irinotecan and cisplatin is effective as a first line therapy in extensive SCLC is effective, but has severe or fatal diarrhea as toxicity.

연구배경: Toptisomerase I 억제제인 irinotecan 과 소세포폐암 치료의 근간인 cisplatin의 복합화학용법을 확장기 소세포폐암 환자에게 1차 치료법으로 실시하여 반응률, 생존율 및 부작용을 확인하였다. 방 법: 2002년 6월부터 2005년 2월까지 확진된 확장기 소세포폐암 환자 39명에게 irinotecan $60mg/m^2$, 제 1, 8, 15일째 cisplatin $60mg/m^2$ 제1일째에 28일 간격으로 4회 투여하였다. 결 과: 반응률은 77%(완전반응 8%), 중앙생존기간은 14.8개월, 1-및 2-년 생존율은 60.9%, 27.6%였으며, 중앙 무진행생존기간은 8.4개월, 6-및 12-개월 무진행생존율은 75.0%, 18.8%였다. WHO grade 3 이상의 부작용은 백혈구 감소증 23%, 설사 26%였으나, 심한 설사때문에 2명은 치료방법을 바꾸었고, 1명은 사망하였다. 결 론: Irinotecan과 cisplatin 복합화학요법은 확장기 소세포폐암 환자의 1차 치료법으로 유용하며, 부작용으로서 설사에 대해서는 치명적일수 있으므로 심각한 주의가 요망된다.

Acknowledgement

Supported by : 원광대학교

References

  1. Jeong ET. Clinical survey of lung cancer in Korea. Tuberc Respir Dis 2000;49:137-48 https://doi.org/10.4046/trd.2000.49.2.137
  2. Witta SE, Kelly K. Chapter 46, chemotherapy for small cell lung cancer ln;Pass HI, Carbone DP, Johnson DH, Minna JD, Turris AT, editors, Lung cancer, 3rd ed. Philadephia: Lippincott Williams and Wilkins:2005. p657-73
  3. Kunimoto T, Nitta K, Tanaka T, Uehara N, Baba H, Takeuchi M, et al. Antitumor activity of 7-ethyl- 10-(4-(1-piperidino)-1-piperidino)carbonyloxy-camptoth ecin, a novel water-soluble derivative of camptothecin against murine tumors. Cancer Res 1987;47:5944-7
  4. Masuda N, Fukuoka M, Takada M, Kusunoki Y, Negoro S, Matsui K, et al. CPT-11: A new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol 1992;10:1225-9
  5. Kudoh S, Fujiwara Y, Takada Y, Yamamoto H, Kinoshita A, Ariyoshi Y, et al. Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group. J Clin Oncol 1998; 16:1068-74
  6. Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002;346:85-91 https://doi.org/10.1056/NEJMoa003034
  7. WHO handbook for reporting the results of cancer treatment. No. 48. Geneva: World Health Organization, 1979
  8. Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, et al. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol 1992;10:282-91
  9. Chute JP, Chen T, Feigal E, Simon R, Johnson BE. Twenty years of phase III trials for patients with extensive-stage small-cell lung cancer: perceptible progress. J Clin Oncol 1999;17:1794-809 https://doi.org/10.1200/JCO.1999.17.6.1794
  10. Hsiang YH, Hertzberg R, Hecht S, Liu LF. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J Biol Chem 1985;260:14873-8
  11. Negoro S, Fukuoka M, Masuda N, Takada M, Kusunoki Y, Matsui K. Phase I study of weekly intravenous infusions of CPT-11, a new derivative of camptothecin, in the treatment of advanced non-small -cell lung cancer. J Natl Cancer Inst 1991;83:1164-8 https://doi.org/10.1093/jnci/83.16.1164
  12. Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, et al. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol 2006;24:2038-43 https://doi.org/10.1200/JCO.2005.04.8595
  13. Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, et al. Prospective randomized comparison of high dose and standard dose etoposide and cisplatin chemotherapy on patients with extensive stage small cell lung cancer. J Clin Oncol 1994; 12:2022-34 https://doi.org/10.1200/JCO.1994.12.10.2022
  14. Beutler E, Gelbart T, Demina A. Racial variability in the UDP-glucuronosyltransferase 1 (UGT1A1) promoter: a balanced polymorphism for regulation of bilirubin metabolism? Proc Natl Acad Sci USA 1998;95:8170-4
  15. Font A, Taron M, Rosell R. UGT1A1 genotyping correlates with toxicity and survival in non-small cell lung cancer (NSCLC) patients treated with secondline CPT-11/docetaxel. Proc Am Soc Clin Oncol 2001;20:340a
  16. Han JY, Lim HS, Shin ES, Yoo YK, Park YH, Lee JE, et al. Comprehensive analysis of UGT1A polymorphisms predictive for pharmacokinetics and treatment outcome in patients With non-small-cell lung cancer treated with irinotecan and cisplatin. J Clin Oncol 2006;24:2237-44 https://doi.org/10.1200/JCO.2005.03.0239
  17. Jeong HL, Lee SY, Kim JH, Ha ES, Jung JY, Lee KJ, et al. Phase II trial of irinotecan plus cisplatin combinations on first line therapy for patients with small cell lung cancer. Tuberc Respir Dis 2005; 60:57-64 https://doi.org/10.4046/trd.2006.60.1.57