Concurrent Chemoradiation for Unresectable Pancreatic Cancer

절제 불가능한 췌장암의 동시항암화학방사선요법

  • Kim, Yong-Bae (Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Seong, Jin-Sil (Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Song, Si-Young (Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Park, Seung-Woo (Department of Internal Medicine, Brain Korea 21 Project for Medical Science, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Suh, Chang-Ok (Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine)
  • 김용배 (연세대학교 의과대학 연세암센터 방사선종양학교실) ;
  • 성진실 (연세대학교 의과대학 연세암센터 방사선종양학교실) ;
  • 송시영 (연세대학교 의과대학 연세암센터 내과학교실, Brain Korea 21 의과학사업단) ;
  • 박승우 (연세대학교 의과대학 연세암센터 내과학교실, Brain Korea 21 의과학사업단) ;
  • 서창옥 (연세대학교 의과대학 연세암센터 방사선종양학교실)
  • Published : 2002.12.01

Abstract

Purpose : To analyze the treatment results of concurrent chemoradiation with oral 5-FU plus Gemcitabine or Paclitaxel for unresectable pancreatic cancer. Materials & Methods : The patients, who were diagnosed by imaging modalities or by explo-laparotomy, were treated with concurrent chemoradiation. Radiotherapy was delivered to primary tumor and regional lymph nodes, and the total dose was 45 Gy. Patients received Gemcitabine $1,000\;mg/m^2$ or Paclitaxel $50\;mg/m^2$ weekly and oral 5-FU daily The total number of cycles of chemotherapy ranged from 1 to 39 (median, 11 cycles). The follow-up period ranged from 6 to 36 months, Survival was analyzed using the Kaplan-Meier method. Results : Fifty-four patients between Jan. 1999 to Nov. 2001 were included in this study. Forty-two patients who completed the planned treatment were included in this analysis. The patients' age ranged from 37 to 73 years (median, 50 years) and the male to female ratio was 30:12. Treatment was interrupted for 12 patients due to: disease progression for 6 $(50\%)$, poor performance status for 4 $(33.3\%)$, intercurrent disease for 1 $(8.3\%)$, and refusal for 1 $(8.3\%)$. Response evaluation was possible for 40 patients. One patient gained complete remission and 24 patients gained partial remission, hence the response rate was $59\%$. The survival rates were $46.7\%\;and\;17.0\%$ at 1 year and 2 years, respectively with a median survival time of 12 months. Patients treated with Paclitaxel showed superior outcomes compared to those patients treated with Gemcitabine, in terms of both response rate and survival rate although this difference was not statistically significant. Grade III or IV hematologic toxicity was shown in 8 patients $(19\%)$, while grade III or IV non-hematologic toxicity was shown in 5 patients $(12\%)$. Conclusion : Concurrent chemoradiation with oral 5-FU and Gemcitabine or Paclitaxel improves both the response rate and survival rate in patients with unresectable pancreatic cancer. A prospective study should be investigated in order to improve both the patient selection and the treatment outcome as well as to reduce the toxicity.

목적 : 절제 불가능한 췌장암은 예후가 불량하여 효과적인 치료법의 개발이 요망되고 있다. 본 연구에서는 Gemcitabine 또는 Paclitaxel과 5-Fluorouracil (5-FU)을 이용한 동시항암화학방사선요법을 시행하여 치료효과를 분석하고자 하였다. 대상 및 방법: 임상적으로 혹은 개복수술 소견 상 절제 불가능한 췌장암으로 진단받은 환자를 대상으로 Gemcitabine 또는 Paclitaxel과 5-FU을 이용한 동시항암화학방사선요법을 시행하였다. 방사선 치료는 원발병소와 주위 림프절을 포함하여 5주 동안 45 Gy를 조사하였다. 이 기간동안 Gemcitabine $1,000\;mg/m^2$ 또는 Paclitaxel $50\;mg/m^2$의 매주 1회 주사 및 5-FU의 매일 경구 투여를 시행하였다. 추적관찰기간은 6개월에서 36개월이었으며, 생존율은 Kaplan-Meier법을 이용하여 분석하였다. 결과 : 1999년 1월부터 2001년 11월까지 본 치료법이 시행된 경우는 54예였으며, 이중 계획된 치료를 종료한 42예를 분석하였다. 남녀 비는 30 : 12였고 중앙 연령은 60세였다. 총 54예 중 치료 중 원격전이나 암종증(carcinomatosis) 등으로의 진행 6명$(50\%)$, 시작시 불량한 전신수행 상태 4명$(33.3\%)$, 병변과 무관한 병발질환 1명$(8.3\%)$, 치료 거부 1명$(8.3\%)$ 등으로 총 12예에서 치료가 중단되었다. 42명의 환자 중 40예에서 반응 평가가 가능하였으며 완전 관해 1예, 부분 관해 24예로 관해율은 $59\%$로 나타났다. 중앙 생존값은 12개월, 1년 생존율은 $46.7\%$, 2년 생존율은 $17.0\%$였다. Grade III 이상의 치료독성으로는 혈액학적 독성이 8예$(19\%)$, 오심, 구토 등의 비혈액학적 독성이 9예$(20\%)$이었다. 이중 2명은 치료독성에 의한 상부 소화기 출혈로 사망하였다. 결론 : 절제 불가능한 췌장암에서 Gemcitabine 또는 Paclitaxel를 이용한 동시항암화학방사선요법은 관해율과 생존율에 있어서 효과적인 치료로 생각된다. 그러나 독성감소를 위한 연구가 또한 병행되어야 할 것으로 생각된다.

Keywords

References

  1. CentraI Cancer Registry Center, Ministry of HeaIth and WeIfare, Korea. Annnal report of the central cancer registry in Korea. 2000
  2. Merrick III HW, DobeIbower RR. Aggressive therapy for cancer of the pancreas-dose it help? Gastroenterol CIin North Am 1990;19:935-962
  3. Lee SJ, Lee YC, Song SY, et aI. Clinical study on pancreatic cancer and its prognostic factors. Korean J Gastroenterol 1994;26:1010-1020
  4. Whang YW, Chang HJ, Lee JK, et aI. Survival and recurrence pattern after cfter curative resection of pancreatic cancer. Korean J Gastroenterol 2001;38:276-283
  5. MoerteI CG, ChiIds DS, Reitemeier RJ, CoIby MY, HoIbrook MA. Combined 5-fluorouraciI and supervoltage radiation therapy of locally unresectabIe gasrointestinal cancer. Lancet 1969;2:865-867
  6. MoerteI CG, Frytak S, Hahn RG, et aI. Therapy of Iocally unreaectabIe pancreatic carcinoma : A randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads+5-fluorouracil), and high dose radiation+5-fluorouracil : The Gastrointestinal Tumor Study Group. Cancer 1981;48:1705-1710
  7. The GastrointestinaI Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas : Comparison of combined-modaIity therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst 1988;80:751-755 https://doi.org/10.1093/jnci/80.10.751
  8. Lawrence TS, Eisbruch A, Shewach DS. Gemcitabinemediated radiosensitization. Semin Oncol 1997;24(2, S7):24-28
  9. Hak C, Rodriguez FF, Koester S, HiIsenbeck S, Von Hoff D. Investigation of Taxol as a potential radiation sensitizer. Cancer 1993;71:3774-8 https://doi.org/10.1002/1097-0142(19930601)71:11<3774::AID-CNCR2820711147>3.0.CO;2-0
  10. BIackstock AW, Bernard SA, Richards F, et aI. Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer. J Clin Oncol 1999;17:2208-2212
  11. Kudrimoti M, Regine W, John W, et aI. Concurrent infusional gemcitabine and radiation in the treatment of advanced unresectabIe GI maIignancy : A phase I/II study. Proc Am Soc Clin Oncol 1999;28:242a
  12. Wong S, Oza AM, BrierIey J, et aI. Phase I study of gemcitabine and escaIating dose radiation therapy in patients with pancreatic carcinoma. Proc Am Soc CIin Oncol 2000;19:268a
  13. MiIas L, Fujii T, Hunter NR, et aI. Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res 1999;59:107-114
  14. Lawrence TS, Chang EY, HerteI L, et aI. Gemcitabine radiosensitizes human pancreatic cancer cells. Proc Am Assoc Cancer Res 1994;35:647
  15. Huang NJ, HitteIman WN. Transient inhibition of chromosome damage repair after after ionizing radiation by gemcitabine. Proc Am Assoc Cancer Res 1995;36:612
  16. Mason KA, MiIas L, Hunter NR, et aI. Maximizing therapeutic gain with gemcitabine and fractionated radiation. Int J Radiat Oncol Biol Phys 1999;44:1125-1135 https://doi.org/10.1016/S0360-3016(99)00134-0
  17. WoIff R, Janjan N, Lenzi R, et aI. Treatment related toxicities with rapid-fractionation external beam radiation and concomitant gemcitabine for Iocally advanced nonmetastatic adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1998;42:201
  18. EpeIbaum R, RosenbIatt E, NasraIIah S, et aI. Phase II study of gemcitabine pancreatic cancer. Eur J Cancer 1999;35:S148-149
  19. Abad A, AreIIano A, Brunet J, et aI. Gemcitabine plus radiotherapy in stage II-III pancreatic cancer : A phase I trial. Ann Oncol 1998;9:53
  20. McGinn CJ, ZaIupski MM, Shureiqi I, et aI. Phase I Trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J CIin Oncol 2001;19:4102-4208
  21. Hoffman JP, McGinn CJ, Ross E, et aI. A Phase I Trial of preoperative gemcitabine for patients with locaIized,resectabIe pancreatic adenocarcinoma. Cancer Invest 1999;17:30-32 https://doi.org/10.3109/07357909909011714
  22. Safran H, King TP, Choy H, et aI. Paclitaxel and concurrent radiation for Iocally advanced pancreatic and gastric cancer : a phase I study. J CIin Oncol 1997;15:901-907
  23. Safran H, Moore T, Iannitti D, et aI. Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2001;49:1275-1279 https://doi.org/10.1016/S0360-3016(00)01527-3
  24. Rowinsky EK, WindIe JJ, Von Hoff DD. Ras protein farnesyltransferase : a strategic target for anticancer therapeutic development. J CIin Oncol 1999;17:3631