Comparison of the Result of Radiation Alone and Radiation with Daily Low Dose Cisplatin in Management of Locally Advanced Cervical Cancer

국소적으로 진행된 자궁경부암에서 방사선 단독치료와 방사선 및 저용량 Cisplatin 항암화학요법 병용치료의 비교

  • Kim Hun Jung (Departments of Radiation Oncology, Inha University Medical College) ;
  • Kim Woo Chul (Departments of Radiation Oncology, Inha University Medical College) ;
  • Lee Mee Jo (Departments of Radiation Oncology, Inha University Medical College) ;
  • Kim Chul Su (Departments of Hemato-Oncology, Inha University Medical College) ;
  • Song Eun Seop (Departments of Obstetrics and Gynecology, Inha University Medical College) ;
  • Loh John J K. (Departments of Radiation Oncology, Inha University Medical College)
  • 김헌정 (인하대학교 의과대학 방사선종양학과교실) ;
  • 김우철 (인하대학교 의과대학 방사선종양학과교실) ;
  • 이미조 (인하대학교 의과대학 방사선종양학과교실) ;
  • 김철수 (인하대학교 의과대학 혈액종양학과교실) ;
  • 송은섭 (인하대학교 의과대학 산부인학과교실) ;
  • 노준규 (인하대학교 의과대학 방사선종양학과교실)
  • Published : 2004.09.01

Abstract

Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

목적: 국소적으로 진행된 자궁경부암 치료에 있어 방사선 단독치료요법과 방사선 및 방사선 민감제로 저용량 Cisplatin으로 병용요법의 치료 성적을 후향적으로 분석하였다. 대상 및 방법: 1996년 12월부터 2001년 3월까지 근치적 방사선치료를 받은 59명의 국소적으로 진행된 자궁경부암 환자를 대상으로 생존율, 반응, 재발양상, 부작용에 대하여 후향적으로 분석을 하였다. 방사선 단독으로 치료한 환자는 31명이며, 저용량 cisplatin을 방사선치료와 병용치료한 환자는 28명이었다. 대상 환자의 추적조사 기간은 2.5개월에서 73개월로 중앙값은 34개월이었다. 방사선치료는 외부방사선치료로 골반강에 4,500 cGy와 자궁방결합조직에 900$\~$l,000 cGy를 추가로 치료하였고, Ir-192 고선량률 근접 치료기(micro-Selectron HDR)로 6$\~$7회 강내조사(point "A"에 3,000$\~$3,500 cGy, 500 cGy/fx, 주 2회)를 시행하였다. 병용치료 군에서는 방사선치료 첫날부터 20일째 되는 날까지 cisplatin 10 mg을 방사선치료 30분 전에 투여하였다 FIGO 병기별로 IIB가 51명(86.4$\%$), IIIB가 8명(13.6$\%$)이고, 조직병리상 54명(91.5$\%$)이 편평상피세포암, 2명(3.4$\%$)이 선암, 3명(5.1$\%$)이 편평상피선암이었다. 결과: 대상환자 59명에 대한 5년 생존율과 무병생존율은 각각 65.7$\%$와 55.8$\%$였다. 치료방법에 따른 결과로 방사선 단독치료군과 병용치료군에서 5년 생존율은 각각 56.8$\%$와 73.4$\%$ (p=0.180)였고, 무병 생존율은 각각 49.4$\%$와 63.3$\%$ (p=0.053)였다. 그리고 5년 국소제어율은 각각 52.3$\%$와 73.6$\%$ (p=0.013)였으며 , 5년 원격제어율은 각각 59.3$\%$와 81.5$\%$ (p=0.477)였다. 급성합병증 중에서 3등급 이상의 백혈구감소(3.2$\%$ vs 28.5$\%$, p=0.02)와, 3등급 이상의 혈소판감소(0$\%$ vs 7.1$\%$, p=0.04)만 병용치료군에서 통계적으로 증가되어 있었다. 만성합병증은 양 군 간에서 의미 있는 차이를 보이지 않았다. 결론: 본 연구 결과 방사선치료와 방사선 민감제로 저용량 Cisplatin의 병용치료방법은 방사선단독치료 방법에 비하여 무병생존율과 국소제어율에는 영항을 미쳤으나, 생존율을 향상시키지는 못했고, 급성독성으로 골수억제의 빈도가 더 높게 나타났다.

Keywords

References

  1. 2002 Annual Report of the Korea Central Cancer Resistry, Ministry of Health and Welfare Republic of Korea
  2. Perez CA, Camel HM, Kuske RR, Kao MS, Galakatos A, Hederman MA. Powers WE. Radiation therapy alone in the treatment of carcinoma of the uterine cervix: 20-year experience. Gynecol Oncol 1986;23:127-140
  3. Perez CA, Breaux S, Madoc-Jones H, et al. Radiation therapy alone in the treatment of carcinoma of uterine cervix: analysis of tumor recurrence. Cancer 1983;51:1393-1402 https://doi.org/10.1002/1097-0142(19830415)51:8<1393::AID-CNCR2820510812>3.0.CO;2-M
  4. Jampolis S, Andras EJ, Fletcher GH. Analysis of sites and causes of failure of irradiation in invasive squamous cell carcinoma of the intact uterine cervix. Radiology 1975;115 :681-685
  5. Lee KJ. Results of radiation therapy for carcinoma of the uterine cervix. J Korean Soc Ther Radiol 1995;13:359-368
  6. Rose PG. Locally advanced cervical carcinoma: the role of chemoradiation. Semin Oncol 1994;21:47-53
  7. Perez CA, Kurman RJ, Stehman FB, et al. Principles and practice of gynecologic oncology. Philadelphia: J. B Lippincott; 1992;591-662
  8. Souhami L, Gil RA, Allan SE, et al. A randomized trial of chemotherapy followed by pelvic radiation therapy in stage III B carcinoma of the cervix. J Clin Oncol 1991;9:970-977 https://doi.org/10.1200/JCO.1991.9.6.970
  9. Morris M, Eifel PJ, Lu J, et al. Pelvic radiation with concurrent chemotherapy compared with pelvic and paraaoritc radiation for high-risk cervical cancer. N Engl J Med 1999; 340:1137-1143 https://doi.org/10.1056/NEJM199904153401501
  10. Keys HM, Bundy BN, Stehman FB, et al. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 1999;340:1154-61 https://doi.org/10.1056/NEJM199904153401503
  11. Whitney CW, Sause W, Bundy BN, et al. Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjuvant to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: A Gynecologic Oncology Group and Southwest Oncology Group Study. J Clin Oncol 1999:17;1339-1348
  12. Schaake-Koning C, van den Bogaert W, Dalesio O, et al. Effects of concomitant cisplatin and radiotherapy on inoperable nonsmall cell lung cancer. N Engl J Med 1992;326:524-530 https://doi.org/10.1056/NEJM199202203260805
  13. Branislav J, Yuta S, Slobadon M, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide: A randomized study. J Clin Oncol 1996;14(4):1065-1070
  14. Horiot J-C, Pigneux J, Pourquier H, et al. Radiotherapy alone in carcinoma of the intact uterine cervix according to GH Fletcher guidelines: A French Cooperative study of 1383 cases. Int J Radiat Oncol Biol Phys. 1988;14:605-611 https://doi.org/10.1016/0360-3016(88)90080-6
  15. Montana GS, Martz KL, Hanks GE. Patterns and sites of failure in cervix cancer treated in the U.S.A in 1978. Int J Radiat Oncol Biol Phys 1991;20:87-93
  16. Lanciano RM, Martz K, Coia LR, et al. Tumor and treatment factors improving outcome in stage III-B cervix cancer. Int J Radiat Oncol Biol Phys 1991;20:95-100 https://doi.org/10.1016/0360-3016(91)90143-R
  17. Kim RY, Trotti A, Wu CJ, et al. Radiation alone in the treatment of cancer of the uterine cervix: Analysis of pelvic failure and dose response relationship. Int J Radiat Oncol Biol Phys 1989;17:973-978 https://doi.org/10.1016/0360-3016(89)90144-2
  18. Kraiphibul P, Srisupundit S, Pairachvet, V, et al. Results of treatment in stage IIB squamous cell carcinoma of the uterine cervix: Comparison between two and one intracavitary insertion. Gynecol Oncol 1992;45:160-163 https://doi.org/10.1016/0090-8258(92)90279-R
  19. Heller PB, Maletano JH, Bundy BN, et al. Clinicalpathologic study of stage IIB, III, and IVA carcinoma of the cervix: Extended diagnostic evaluation for paraaortic node metastasis-a Gynecologic Oncology Group study, Gynecol Oncol 1990;38:425-430
  20. Kovalic JJ, Perez CA, Grigsby PW, et al. The effect of volume of disease in patients with carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 1991;21:905-910 https://doi.org/10.1016/0360-3016(91)90728-M
  21. Fowler JF, Lindstrom MJ. Loss of local control with pro longation in radiotherapy. Int J Radiat Oncol Biol Phys1992;23:457-467 https://doi.org/10.1016/0360-3016(92)90768-D
  22. Denkamp J. Changes in the rate of repopulation during multifraction irradiation of mouse skin. Br J Radiol 1973;46:381-387 https://doi.org/10.1259/0007-1285-46-545-381
  23. Withers HR, Taylor MG, Maciejewski B. The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 1988;27:131-146 https://doi.org/10.3109/02841868809090333
  24. Leibel S, Bauer M, Wasserman T, et al. Radiotherapy with or without misonidazole for patients with stage IIIB or stage IV squamous cell carcinoma of the uterine cervix: Preliminary report of a Radiation Therapy Oncology Group randomized trial. Int J Radiat Oncol Biol Phys 1987;13: 541-549 https://doi.org/10.1016/0360-3016(87)90069-1
  25. Stehman FB, Bundy BN, Thomas G, et al. Hydroxyurea versus misonidazole with radiation in cervix carcinoma: longterm follow-up of a Gynecologic Oncology Group trial. J Clin Oncol 1993;11:1523-1528 https://doi.org/10.1200/JCO.1993.11.8.1523
  26. Piver MS, Barlow JJ, Vongtama V, et al. Hydroxyurea: a radiation potentiator in carcinoma of the uterine cervix. A randomized double-blind study. Am J Obstet Gynecol 1983;147:803-808
  27. Johnson RJ, Walton RJ. Sequential study on the effect of the addition of hyperbaric oxygen on the 5 year survival rates of carcinoma fo the cervix treated with conventional fractional irradiations. AJR 1974;120:111-117 https://doi.org/10.2214/ajr.120.1.111
  28. Ward AJ, Dixon B. Carcinoma of the cervix: results of a hyperbaric oxygen trial associated with the use of the cathetron. Clin Radiol 1979;30:383-387 https://doi.org/10.1016/S0009-9260(79)80213-5
  29. Heaton D, Yordan E, Reddy S, et al. Treatment of 29 patients with bulky squamous cell carcinoma of the cervix with simultaneous cisplatin, 5-fluorouracil, and split-course hyperfractionated radiation therapy. Gynecol Oncol 1990;38:323-327 https://doi.org/10.1016/0090-8258(90)90066-T
  30. Komaki R, Pajak TF, Marcial VA, et al. Twice-daily fractionation of external irradiation with brachytherapy in buky carcinoma of the cervix: Phase I/II study of the RadiationTherapy Oncology Group 88-05. Cancer 1994;73:2619-2625 https://doi.org/10.1002/1097-0142(19940515)73:10<2619::AID-CNCR2820731025>3.0.CO;2-P
  31. Resbeut M, Cowen D, Viens P, et al. Concomitant chemoradiation prior to surgery in the treatment of advanced cervical carcinoma. Gynecol Oncol 1994;54:68-75 https://doi.org/10.1006/gyno.1994.1168
  32. Prempree T. Parametrial implant in stage IIIB cancer of the cervix. A five-year study. Cancer 1983;52:748-750 https://doi.org/10.1002/1097-0142(19830815)52:4<748::AID-CNCR2820520431>3.0.CO;2-O
  33. Zak M, Drobnik J. Effects of cis-dichlorodiamine-platinum on the post-irradiation lethality in mice after irradiation with X-rays. Strahlentherapie 1971;142:112-115
  34. Douple EB, Richmond RC. A review of platinum complex biochemistry suggests a rationale for combined platinumradiotherapy. Int J Radiat Oncol Biol Phys 1979;5:1335-1339 https://doi.org/10.1016/0360-3016(79)90665-5
  35. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al. Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 2000:18;1606-1613
  36. Rose PG, Bundy BN, Watkins EB, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cacner. N Engl J Med 1999;340:1144-1153 https://doi.org/10.1056/NEJM199904153401502
  37. Perez CA, Kao MS. Radiation therapy alone or combined with surgery in the treatment of barrel-shaped carcinoma of the uterine cervix stage IB, IIA, IIB. Int J Radiat Oncol Biol Phys 1985;11:1903-1909 https://doi.org/10.1016/0360-3016(85)90270-6
  38. Eifel PJ. Thoms WW, Smith TL, et al. The relationship between brachytherapy dose and outcome in patinets with bulky endocervical tumors treated with radiation dose. Int J Radiat Oncol Biol Phys 1994;28:113-118 https://doi.org/10.1016/0360-3016(94)90148-1
  39. Ohara K, Tanaka YO, Tsunoda, et al. Nonoperative assessment of nodal status for locally advanced cervical squamous cell carcinoma treated by radiotherapy with regard to patternns of treatment failure. Int J Radiat Oncol Biol Phys 2003;55:354-361 https://doi.org/10.1016/S0360-3016(02)03930-5