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Metastatik Kolorektal Kanserde Kurtarma Tedavisi:Regorafenib

Giriş: Kolorektal kanser (KRK), kanser ilişkili ölümlerin önemli nedenlerinden biridir. Bu çalışmanın amacı, metastatik KRK hastalarında regorafenib tedavisinin etkinlik ve toksisite profilini değerlendirmektir. Method: Bu çalışmada tek merkezde takip edilen 25 mKRK hastasının retrospektif verileri incelenmiştir. Tüm hastalarda biyolojik ajanlar olan anti-epidermal büyüme faktörü reseptörü (anti-EGFR) ve anti-vasküler endotelyal büyüme faktörü (anti-VEGF) ile kombine olarak veya olmaksızın 5-fluorourasil, irinotekan ve okzaliplatin ile progresyon saptanmıştı. Bulgular: Ortanca yaş 58 (dağılım 27-84) idi, ve 14 erkek ve 11 kadın vardı. Hastalar regorafenib başlangıcından önce ortanca 3 sıra sistemik tedavi aldılar. En sık görülen derece 3. veya 4. derece toksisiteler yorgunluk %20, daire %16 ve mukozit %16 idi. Ortanca PFS 2.07 ay (0.43-5.13) ve ortanca OS 4.14 ay (0.62-19.88) idi. Tek değişkenli analizde hiçbir faktör PFS ve OS ile ilişkili bulunmadı. Sonuç: Regorafenib, standart tedavilerdeki başarısızlıktan sonra başka tedavi seçeneği bulunmayan metastatik KRK hastalarında küçük fakat önemli bir sağkalım yararı göstermektedir. Prediktif faktörlerin olmamasıyla birlikte toksisite profili klinik uygulamada kullanılmadan önce dikkatli bir değerlendirme yapılmasını önerir.

Anahtar Kelimeler:

kolorektal kanser, regorafenib, yan etki

Salvage Treatment Option for Metastatic Colorectal Cancer:Regorafenib

Introduction: Colorectal cancer (CRC) is an important cause of cancer-related deaths. The aim of this study was to evaluate the efficacy and toxicity profile of regorafenib treatment in metastatic CRC patients.Methods: This was a retrospective study of 25 mCRC patients from a single center. All patients had previously progressed fluorouracil, irinotecan, and oxaliplatin with or without biologic agents such as epidermal growth factor receptör (anti-EGFR) or vascular endothelial growth factor receptor (anti-VEGF).Results: The median age was 58 years (range, 27 to 84 years), and there were 14 males and 11 females. Patients had received a median of 3 lines of systemic therapy before regorafenib initiation. The most common grade 3 or 4 toxicities were fatigue 20%, daire 16% and mucositis 16%. Median PFS was 2.07 months (0.43-5.13) and median OS was 4.14 months (0.62-19.88). No factors were significantly associated with PFS and OS in the univariate analysis. Conclusion: Regorafenib shows a small but significant survival benefit in patients with metastatic CRC who do not have any further treatment options after the failure over standard therapies. Its toxicity profile along with the absence of predictive factors suggest a careful evaluation before its use in clinical practice

Keywords:

colorectal cancer, regorafenib, toxicity,

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Referans1.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016.CA Cancer J Clin 2016;66(1):7-30
Referans2. Abrahao ABK, Ko YJ, Berry S, Chan KKW. A Comparison of regorafenib and TAS-102 for metastatic colorectal cancer: a systematic review and network meta-analysis. Clin Colorectal Cancer 2018; 17: 113-20
Referans3. Garcia-Alfonso P, Feliu J, Garcia-Carbonero R, Gravalos C, Guillen-Ponce C, Sastre J, et al. Is regorafenib providing clinically meaningful benefits to pretreated patients with metastatic colorectal cancer? Clin Transl Oncol 2016; 18: 1072-81
Referans4. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381: 303-12
Referans5. Kim ST, Kim TW, Kim KP, Kim TY, Han SW, Lee SH et al. Regorafenib as Salvage Treatment in Korean Patients with Refractory Metastatic Colorectal Cancer. Cancer Res Treat. 2015 Oct; 47(4): 790–795
Referans6. Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, et al. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2015; 16: 619-29
Referans7. Sartore-Bianchi A, Zeppellini A, Amatu A, Ricotta R, Bencardino K, Siena S. Regorafenib in metastatic colorectal cancer. Expert Rev Anticancer Ther 2014;14:255–65
Referans8. Ganesan P, Sagar TG, Dubashi B, Rajendranath R, Kannan K, Cyriac S, et al. Nonadherence to imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia. Am J Hematol 2011;86:471-4
Referans9. Hershman DL, Shao T, Kushi LH, Buono D, Tsai WY, Fehrenbacher L, et al. Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat 2011;126:529-37
Referans10. Seal BS, Anderson S, Shermock KM. Factors associated with adherence rates for oral and intravenous anticancer therapy in commercially insured patients with metastatic colon cancer. J Manag Care Spec Pharm 2016;22:227-35
Referans11. Liu G, Franssen E, Fitch M, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol 1997;15:110-5
Referans12. Shitara K, Yamanaka T, Denda T, Tsuji Y, Shinozaki K, Komatsu Y, et al. REVERCE: a randomized phase II study of regorafenib followed by cetuximab versus the reverse sequence for previously treated metastatic colorectal cancer patients. Ann Oncol 2019;30(2):259-265
Referans13. De Wit M, Boers-Doets CB, Saettini A, Vermeersch K, de Juan CR, Ouwerkerk J, et al. Prevention and management of adverse events related to regorafenib. Supportive Care Cancer 22(3), 837–846 (2014)
Referans14. Grothey A, George S, van Cutsem E, Blay JY, Sobrero A, Demetri GD. Optimizing treatment outcomes with regorafenib: personalized dosing and other strategies to support patient care. Oncologist 2014:19(6), 669–680
Referans15. Khan G, Moss RA, Braiteh F, Saltzman M. Proactive strategies for regorafenib in metastatic colorectal cancer: implications for optimal patient management. Cancer Manag Res 2014. 6, 93–103
Referans16. Adenis A, de la Fouchardiere C, Paule B, Burtin P, Tougeron D, Wallet J, et al. Survival, safety, and prognostic factors for outcome with Regorafenib in patients with metastatic colorectal cancer refractory to standard therapies: results from a multicenter study (REBECCA) nested within a compassionate use program. BMC Cancer 2016; 16: 412