Kerim CAYIR, Mehmet BİLİCİ, Salim Başol TEKİN, Habip EMRE, YUSUF BİLEN

Evre II-III kolon kanserli hastalarda adjuvan tedavinin yan etki proflinin değerlendirilmesi

Amaç: Bu çalışmada operasyon sonrası adjuvan kemoterapi uygulanan evre II-III kolon kanserli hastaların sonuçlarının toksisite ve tedaviye uyum açısından değerlendirilmesi amaçlanmıştır. Gereç ve Yöntem: Bu çalışmaya İç Hastalıkları Ana Bilim Dalı Medikal Onkoloji Bilim Dalı’nda takip ve tedavileri yapılan ve Aralık 2000-Aralık 2007 tarihleri arasında opere edilen evre II ve III kolon kanserli hastalar dâhil edildi. Rektum kanseri olup, tanı anında metastatik evrede olan hastalar çalışma dışı bırakıldı. Çalışmaya alınan toplam 51 hastanın 11 tanesi (%21.6) herhangi bir kemoterapi almadı ve/veya kendilerine kemoterapi önerilmedi. 30 hasta (%58.8) FUFA (5 Fluoro-urasil/leucoverin) kemoterapi rejimini almış olup, geriye kalan 10 hasta (%19.6) FOLFOX (Oxaliplatin/5 Fluoro-urasil/leucoverin) tedavi rejimini aldı. Tedavi sonrası ortaya çıkan toksisiteler ve hastaların tedaviye uyumları değerlendirildi. Bulgular: FUFA tedavisi alan hastalar yan etki bakımından değerlendirildiğinde; nötropeni ve nötropenik ateş dışında, planlanan tedavileri tamamlama, mukozit ve ishal oranları açısından tedaviye daha iyi uyum sağladıkları ve daha az yan etki ile karşılaştıkları görüldü. Oksaliplatin içeren FOLFOX rejimi ile tedavi edilen hastaların sonuçları yan etki açısından incelendiğinde; başlangıçta planlanan tedaviyi alma oranları, tedavi ile ilişkili diare oranları olağan sıklıkta olup tedavi ile ilişkili nötropeni, nötropenik ateş ve nöropati açısından ise literatür bilgileriyle farklılıklar bulunmaktadır. Sonuç: Opere kolon kanserli gerek evre II gerek evre III hastalarımızda adjuvan kemoterapi uygulamaları sırasında daha az sıklıkta yan etki ile karşılaşmışlardır.

Evaluation of the adverse effect profle of the adjuvant treatment in patients with stage II-III colon cancer

Objectives: The aim of this study was to evaluate compliance of the stage II-III colon cancer patients to the adjuvant chemotherapy and to investigate the results of adjuvant chemotherapy in terms of toxicity in the same group of patients. Materials and Methods: Operated, stage II and III colorectal cancer patients post-operatively followed in Department of Internal Medicine, Division of Medical Oncology between December 2000 and December 2007 were enrolled into this study. Patients who were diagnosed as rectal cancer or who had metastases were excluded. Eleven (21.6%) of the 51 patients either did not accept chemotherapy or adjuvant chemotherapy was not offered. Thirty (58.8%) patients treated with FUFA (5 Fluoro-urasil/leucoverin) chemotherapy regimen and the resting 10 (19.9%) patients were treated with FOLFOX (Oxaliplatin/5 Fluoro-urasil/leucoverin) chemotherapy regimen. Toxicities that emerged after treatment and patient adherence to treatment was evaluated. Results: Patients who were treated with FUFA chemotherapy regimen had better percentages of chemotherapy regimen completion, lesser mucositis and diarrhea rates, except neutropenia and neutropenic fever. Evaluation of patients who were treated with FOLFOX chemotherapy regimen that includes oxaliplatin revealed that completion of chemotherapy regimen rate and chemotherapy-associated diarrhea rates were similar with the literature. There were differences between our results and literature in rates of neutropenia, neutropenic fever and neuropathy. Conclusions: Less adverse effects were seen in adjuvant chemotherapy application of operated colorectal cancer patients with either stage II or stage III.

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1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71–96
2. http://www.nccn.org/professionals/physican_gls/PDF/colon. pdf.
3. Çelik İ, Güllü İ, Barışta İ. Kanser Tedavi Prensipleri ve İlaçlar. İçinde İliçin G, Biberoğlu K, Süleymanlar G, Ünal S(editörler):İç Hastalıkları, 2.baskı. Ankara: Güneş Kitabevi, 2003:2052-2074.
4. Laurie JA, Moertel CG, Fleming TR, et al.Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and combination of levamisole and fuorouracil. The North Central Cancer Treatment Group and the Mayo Clinic. J Clin Oncol 1989;1447-56.
5. O’ Connell MJ, Mailliard JA, Kahn MJ, et al. Controlled trial of fuorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 1997;15:246-50.
6. Andre T, Boni C, Mounedji-Boudiaf L, et al. Multicenter international study of oxaliplatin/ 5-fuorouracil/leucovorinin adjuvant treatment of colon cancer (MOSAIC) investi-
gators. Oxaliplatin, fuorouracil, and leucovorinas adjuvant treatment for colon cancer. N Eng J Med 2004;350:2343-51.
7. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.html #ctc_archive.
8. de Gramont A, Boni C, Navarro M et al. Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and III colon cancer: effcacy results with a median follow-up of 4 years. J Clin Oncol. 2005;23:16S(June 1 suppl).
9. International Multicentre Pooled Analysis of Colon Cancer Trials(IMPACT). Effcacy of adjuvant fuorouracil and folinic acid in colon cancer. Lancet 1995;345:939-44.
10. Wolmark N, Rockette H, Mamounas E, et al. Clinical trials to assess the relative effcacy of fuorouracil and leucovorin, fuorouracil and levamisole, and fuorouracil, leucovorin, and levamisole in patients with Dukes’B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C–04. J Clin Oncol 1999;17:3553–59.
11. Schrag D, Rifas-Shiman S, Saltz L, et al. Adjuvant chemotherapy use for Medicare benefciaries with stage II colon cancer. J Clin Oncol 2002;20:3999-4005.
12. Benson AB, Schrag D, Somerfeld MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408-19.
13. Kuebler JP, Wieand HS, O’ Connel MJ, et al. Oxaliplatin combined with weekly bolus fuorouracil and leucovorin as surgical adjuvant chemotherapy for satge II an stage III colon cancer results from NSABP C-07. J Clin Oncol 2007;25:2156-58.
14. Casidy J, Scheithauer, McKendrick H, et al. Capecitabine (X) vs bolus 5FU/leucovorin (LV) as adjuvant therapy for colon cancer (the X-ACT study): effcacy results of a phase III trilal. Proc Am Soc Clin Oncol 2004;23:3509-13.
15. Wolmark N, Bryant J, Smith R, et al. Adjuvant 5 fuorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project Protocol C-05. J Natl Cancer Ins. 1998;90:1810-16.
16. Petrioli R, Pascucci A, Francini E, et al. Neurotoxicity of FOLFOX- 4 as adjuvant treatment for patients with colon and gastric cancer: a randomised study of two different schedules of oxaliplatin. Cancer Chemother Pharmacol 2008;61:105-11.
17. Gamelin L, Boisdron-Celle, Delva R, et al. Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-fuorourocil and leucovorin for advanced colorectal cancer. Clin Cancer Res 2004;10:4055-61
18. Muto O, Ando H, Ono T, et al. Reduction of oxaliplatinrelated neurotoxicity by calcium and magnesium infusions. Gan To Kagaku Ryoho 2007;34:579-81.
19. Kummar S, Norohna V, Chu E. Antimetabolites. In: DeVita VT, Hellman S, Rosenberg AS, eds. Cancer Principles&Practice of Oncology, 7th edn. Philadelphia: Lippincott Williams&Wilkins, 2005:358-374.