Rektum Kanseri Tanısıyla Radyoterapi ile Eş Zamanlı 5-Florourasil/Kapesitabin Uygulanan Hastaların 10 Yıllık Sağkalımına Etki Eden Faktörlerin Retrospektif Değerlendirilmesi

Abstract

Lokal ileri evre rektum kanseri tanısıyla, radyoterapi (RT) ile eş zamanlı 5-florourasil (5-FU) /kapesitabin uygulanan hastaların 10 yıllık sağkalım sonuçlarını ve sağkalıma etki eden faktörleri incelemeyi amaçladık. Mart 2004-Ocak 2007 arasında Radyoterapi Merkezi’nde radyoterapi ile eş zamanlı 5-florourasil/kapesitabin uygulanan lokal ileri evre rektum adenokarsinomu tanılı 81 hasta (55 5-FU, 26 kapesitabin) retrospektif değerlendirildi. Hastaların nüks ve metastaz durumu ve yaş, T evresi, N evresi, patoloji, müsin komponent varlığı, vasküler invazyon, perinöral invazyon, lenfatik invazyon, lenfositik infiltrasyon, extrakapsüler invazyon, RT tipi, RT dozunun hastalıksız sağkalım (HSK) ve genel sağkalıma (GSK) etkisi araştırıldı. Medyan 35 aylık izlem süresi sonunda, kapesitabin uygulanan 26 hastada lokal nüks gelişmezken, üç hastada (%11) metastaz, 16 hastada (%61) ölüm olmuştur. 5-FU kolunda 55 hastanın 11'inde (%20) lokal nüks saptanmış, 13 hastada (%23) metastaz gelişmiş, 42 hasta (%76) ölmüştür. Kapesitabin için genel sağkalım medyan 24 ay (1-229), hastalıksız sağkalım medyan 36 aydır (1-229). İstatistiksel analizde N evresi (p=0.034), müsin komponent varlığı (p=0.039), vasküler invazyon varlığı (p=0.02) ve radyoterapi dozu (p=0.025) GSK ile ilişkili; yaş (p=0.041), lenfositik infiltrasyon varlığı (p=0.032) ve RT dozu (p=0.04) HSK ile ilişkili saptanmıştır. Literatürle uyumlu olarak çalışmamızda olarak vasküler invazyon ve lenf nodu evresinin (N) GSK'ya istatistiksel anlamlı olarak etkili olduğunu saptadık. Lokal ileri evre rektum kanseri tedavisinde kapesitabinin iyi tolere edilmesi, tedaviye hasta uyumunun yüksek olması, 10 yıllık sağkalım sonuçlarının iyi olması; kemoradyoterapide günümüzde öncelikli olarak tercih edilmesini açıklamaktadır.

Keywords

• rektum kanseri
• kemoradyoterapi
• 5-florourasil
• kapesitabin

Retrospective Evaluation of Factors Affecting 10-Year Survival in Patients with Rectal Cancer Treated with 5-Fluorouracil/Capecitabine Concomitant to Radiotherapy

Abstract

We evaluated the 10-year survival results and factors affecting the survival of patients with locally advanced rectal cancer, who received 5-fluorouracil (5-FU) / capecitabine chemoradiotherapy. Between March 2004 and January 2007, 81 patients administered 5-FU/capecitabine (55 5-FU, 26 capecitabine) concurrently with radiotherapy (RT) at Radiotherapy Center, were evaluated retrospectively. The presence of recurrence and metastasis, and the effects of age, T stage, N stage, pathology, vascular invasion, perineural invasion, lymphatic invasion, lymphocytic infiltration, extracapsular invasion, presence of mucin component, RT type, the dose of RT on disease-free survival (DFS) and overall survival (OS) were analyzed. At the end of a median follow-up period of 35 months, in the capecitabine arm none of 26 patients had a recurrence, three (%11) had metastases, 16 (%61) died. In the 5-FU arm, 11 patients (%20) had a recurrence, 13 (%23) had metastases, 42 (%76) died. For capecitabine, the median OS is 24 months (1-229), and DFS is 36 months (1-229). In statistical analysis, N stage (p=0.034), presence of vascular invasion (p=0.02), presence of mucin component (p=0.039) and radiotherapy dose (p=0.025) were associated with OS; age (p=0.041), presence of lymphocytic infiltration (p=0.032), and the dose of RT (p=0.04) were found to be associated with PFS. Consistent with the literature, we found that lymph node stage (N) and vascular invasion had a statistically significant effect on OS. Better patient compliance with capecitabine, and good 10-year survival results; explain to us why it is the first choice in rectal cancer chemoradiotherapy today.

Keywords

• rectal cancer
• chemoradiotherapy
• 5-fluorouracil
• capecitabine

References

1. Leslie A1, Carey FA, Pratt NR, Steele RJ . The colorectal adenoma-carcinoma sequence. Br J Surg. 2002 ; 89(7): 845.
2. Gatta G, Ciccolallo L, Capocaccia R. EUROCARE Working Group. Differences in colorectal cancer survival between Europian and US populations: The importance of subsite and morphyology. Eur J Cancer 2003; 39(15):2214–22.
3. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990; 264(11):1444–50.
4. Martling AL, Holm T, Rutqvist LE, Johansson H, Moran BJ, Heald RJ, Cedermark B. Impact of a surgical training programme on outcome of rectal cancer in County of Stockholm. Stockholm Colorectal Cancer Study Group. Basingstoke Bowel Cancer Research Project Lancet 2000;356:93-6.
5. Wibe A, Moller B, Norstein J, Carlsen E, Wiig JN, Heald RJ, Landmark F, Myrvold HE, Soreide O. A national strategic change in treatment policy for rectal cancer-implementation of total mesorectal excision as routine treatment in Norway. A national audit. Dis Colon Rectum 2002;45:857-66.
6. Kapiteijn E, Putter H, Van de Velde CJ. Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in The Netherlands. Br J Surg 2002;89:1142-9.
7. Quirke P, Training and Quality assurance for rectal cancer: 20 years of data is enough. Lancet Oncology 2003; 4(11): 695-702.
8. Heald RJ, Husband EM, Ryall RDH. The mesorectum in rectal cancer surgey-the clue to pelvic recurrence. British Journal of Surgey 1982, 69(10): 613-6 (:0007-1323).

9. Heald RJ, Moran BJ, Rayall RDH, Sexton R, Mac Farlane JK. Rectal cancer-The Basingstoke experince of total mesorectal excision, 1978-1997. Archieves of surgery 1998; 133(8): 894-8.
10. Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1986;1:1479-82
11. Stockholm Colorectal Cancer Study Group. Randomised study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncol 1996; 3:423–30.
12. Dahl O, Horn A, Morild I Halvorsen JF, Odland G, Reinertsen S, Reisaeter A, Kavli H and Thunold J. Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway. Cancer 1990;66:2286-94.
13. Goldberg PA, Nicholls RJ, Porter NH, Love S, Grimsey JE, Long-term results of a randomised trial of short-course low-dose adjuvant preoperative radiotherapy for rectal cancer: reduction in local treatment failure. Eur J Cancer 1994;30A:1602-6.
14. Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomised trial. Stockholm Colorectal Cancer Study Group. Cancer 1995; 75:2269-75.
15. Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med 1997;336:980-7.
16. Medical Research Council Rectal Cancer working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet 1996;348:1605-10.
17. Marsh PJ, James RD, Schofield PF. Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective randomised trial. Dis Colon Rectum 1994;37:1205-14.
18. Thomas PR, Lindblad AS. Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a rewiev of the Gastrointestinal Tumor Study Group experience. Radiother and oncol 1988;13:245-52.
19. Fisher B, Wolmark N, Rockette H, Redmond C,Deutsch M, Wickerham DL et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer:results from NSABP protocol R-01. J Natl Cancer Inst 1988;80:21-9.
20. Buyse M, Zeleniuch-Jacquotte A, Chalmers TC. Adjuvant therapy of colorectal cancer. Why we stil don’t know. JAMA 1988;259:3571-8.
21. Krook JE, Moertel GG, Gunderson LL, Wieand HS, Collins RT, Beart RW et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709-15.
22. Gray R, Hills R, Stowe R, Clarke M, Petro R, Buyse M, Piedbors p. Adjuvan radiotherapyfor rectal cancer: A systemic overwiev of 8507 patients from 22 randomised trials. Lancet 2001; 358 (9290): 1291-304.
23. Gray R, Hills R, Stowe R, Clarke M, Petro R, Buyse M, Piedbors p. Adjuvan radiotherapyfor rectal cancer: A systemic overwiev of 8507 patients from 22 randomised trials. Lancet 2001; 358 (9290): 1291-304.
24. Tveit KM, Guldvog I, Hagen S, Trondsen E, Harbitz T, Nygaard K, Nilsen JB and Wist E. Randomised controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer. Norwegian Adjuvant Rectal Cancer Project Group. B J Surg 1997;84:1130-5.
25. Grem JL. Systemic treatment options in advanced colorectal cancer: Perspectives on combination 5-fluorouracil plus leucovorin. Semin Oncol 1997; 24 (Suppl.18): 8-18.
26. Payne SA. A study of quality of life in cancer patients receiving palliative chemotherapy. Soc Sci Med 1992; 35: 1505-9.
27. Miwa M, Ura M, Nishida M, et al. Design of a novel oral fluoropyrimidine capecitabine, wich generates 5-Fluorouracil selectivly in tumours by enzyms concentreated in human liver and cancer tissue . Eur J Cancer 1998; 34: 1274-81.
28. Hoff PM, Ansari R, Batist G, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: Results of a randomized phase III study. J Clin Oncol 2001; 19: 2282-92. 15. Cutsem EV, Twelves C, Cassidy J, et al. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: Results of a large phase III study. J Clin Oncol 2001; 19: 4097-4106.
29. Cutsem EV, Hoff PM, Harper P, et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: Integrated efficacy data and novel analyses from two large, randomized, phase III trials. Br J Cancer 2004; 90: 1190-7.
30. Dunst J, Reese T, Sutter T, et al. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol 2002; 20: 3983-91.
31. Kim JS, Cho MJ, Song KS, et al. Preoperative chemoradiation using oral capecitabine in LARC. Int J Radiat Oncol Biol Phys 2002; 54: 403-8.
32. Kim JC, Kim TW, Kim JH, et al. Preoperative concurrent radiotherapy with capecitabine before total mesorectal excision in LARC. Int J Radiat Oncol Biol Phys 2005; 63: 346-53.
33. De Paoli A, Chiara S, Luppi G, et al. Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: A multicentric phase II study. Ann Oncol 2006; 17: 246-51. 34. Souglakos J, Androulakis N, Kakolyris S, et al. Multicenter dose-finding study of concurrent capecitabine and radiotherapy as adjuvant treatment for operative rectal cancer. Int J Radiat Oncol Biol Phys 2003; 56: 1284-7.
34. Jin J, Lin YX, Liu YP, et al. A phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer. Int J Radiat Oncol Biol Phys 2006; 64: 725-9.
35. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer statistics, 2002. CA J Clin 2005; 55: 74-108.
36. Thrall MM, Wood P, King V, Rivera W, Hrushesky W. Investigation of the comparative toxicity of 5-FU bolus versus 5-FU continuous infusion circadian chemotherapy with concurrent radiation therapy in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2000; 46: 873-81.
37. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol 2001; 19: 2282-92
38. Chiara S, Nobile MT, Barzacchi C, Sanguineti O, Vincenti M, Di Somma C, Meszaros P, Rosso R. Hand-foot syndrome induced by high-dose, short-term, continuous 5-fluorouracil infusion. Eur J Cancer 1997; 33: 967-9.
39. Van Cutsem E, Hoff PM, Harper P et al. Oral capecitabine vs intravenous 5-fluorouracil and leucovorin: integrated efficacy data and novel analyses from twolarge, randomized, phase III trials. Br J Cancer 2004; 90: 1190–1197.
40. Twelves C, Wong A, Nowacki MP et al. Capecitabine as adjuvant treatment forstage III colon cancer. N Engl J Med 2005; 352: 2696–2704.
41. Dunst J, Reese T, Sutter T et al. Phase I trial evaluating the concurrentcombination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol2002; 20: 983–991
42. Lin E, Skibber J, Delcos M et al. A phase II study of capecitabine andradiotherapy plus concomitant boost in patients with locally advanced rectalcancer (LARC): Preliminary safety analysis. Proc Am Soc Clin Oncol 2003; 22:287 (Abstr 1152).
43. Dunst J, Reese T, Hoelscher T et al. Capecitabine combined with radiotherapyas neoadjuvant treatment of locally advanced rectal cancer. Proc Am Soc ClinOncol 2003; 22: 277 (Abstr 1113).
44. Wong SJ, Sadasiwan C, Erickson B et al. A phase II trial of pre-operativecapecitabine and concurrent radiation for locally advanced rectal cancer. ASCOAnnual Meeting Proceedings (Post-Meeting Edition) 2004. J Clin Oncol 2004; 22:(Abstr 3771) 312.
45. De Paoli A, Chiara S, Luppi G et al. A phase II study of capecitabine (CAP)and pre-operative radiation therapy (RT) in resectable, locally advanced rectalcancer (LARC). ASCO Annual Meeting Proceedings (Post-Meeting Edition) 2004.J Clin Oncol 2004; 22: (Abstr 3540) 255.