Metastatik kolorektal kanserlerde uzun infüzyon 5-fu/fa ile ıv bolus 5-fu/fa/irinotekanın etkinlik ve yan etkilerinin gözlemlenmesi
Observation of the effects and adverse effects of infusional 5-fu/fa and ıv bolus 5-fu/fa/irinotecan in metastic colorectal cancer
Yazar: ÖZLEM ÇOBAN YÜKSEL
Danışman: PROF.DR. MUSTAFA ALTINBAŞ
Erciyes Üniversitesi / Tıp Fakültesi / İç Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2005
Konu: Onkoloji = Oncology

Özet:
ÖZETAmaç: Metastatik kolorektal kanser tedavisinde klasik ilaç olan 5-fluorourasil/folinik asit (5-FU/FA)' e eklendiğinde sağ kalım avantajı sağlayan ilkilaç irinotekandır. Bu çalışmada intravenöz (iv) uzun infüzyon (22 saat) şeklindeverilen 5-FU/FA kombinasyonu ile iv bolus şeklinde verilen 5-FU/FA'e eklenenirinotekan kombinasyonunun etkinlik ve yan etkisinin gözlemlenmesi planlandı.Amacımız, uzun infüzyon 5-FU/FA ile bolus 5-FU/FA+irinotekan kombinasyonunuetkinlik ve yan etkiler yönünden karşılaştırmaktır.Hastalar ve Yöntem: Otuz metastatik kolorektal kanserli hasta çalışmaya alındı.Hastaların tümünde histopatolojik olarak ispatlanmış kolon ya da rektum kanseri vegörüntüleme yöntemleri ile gösterilmiş en az bir metastaz odağı vardı. Hastalarmetastatik hastalık için birinci sıra olarak tedavi edildi. 30 hasta iki kola ayrıldı.Birinci (A) kola 5-FU 425 mg/m2 /gün beş gün iv bolus, FA 20 mg/m2/gün beş güniv bolus, irinotekan (CPT-11) 180 mg/m2 1.gün 90 dakika iv infüzyon şeklinde 28gün ara ile uygulandı. kinci (B) kola 5-FU 1000 mg/m2/gün beş gün 22 saat ivinfüzyon, FA 100 mg/m2/gün beş gün 2 saat iv infüzyon şeklinde 28 gün ara ileuygulandı. Objektif cevap oranı, tedavi yararlanımı, yaşam süreleri ve yan etkilerdeğerlendirildi.Bulgular: Çalışmada 17'si (%56.7) kadın, 13'ü (%43.3) erkek toplam 30 hastadeğerlendirildi. Hastaların 14'ü 1.grupta (A), 16'sı 2.grupta (B) kemoterapi aldı.Hasta sayısı, cinsiyet, yaş, performans durumu ve uygulanan kür sayısı açısındangruplar arasında fark yoktu. Otuz hastaya toplam 145 kür kemoterapi uygulandı.A kolunda medyan 5.5 (2-6) , B kolunda medyan 6 (3-6) kür kemoterapi verildi. Agrubunda 1 hasta (%7.1) tedaviye tam cevap, 1 hasta (%7.1) kısmi cevap verirken(objektif cevap oranı %14.3), 4 hasta (%28.6) stabil olarak kabul edildi (tedaviyararlanımı %42.9). B grubunda ise 1 hasta (%6.3) tedaviye tam cevap, 3 (%18.8)hasta kısmi cevap verirken (objektif cevap oranı %25), 4 hasta (%25) stabil hastalıkolarak kabul edildi (tedavi yararlanımı %50). Progresyonsuz sağ kalım A grubundamedyan 9Â±2.0 ay (%95 GA 5-13), B grubunda medyan 7Â±2.0 aydı (%95 GA 3-11).vGenel sağ kalım (OS) A grubunda medyan 16Â±3.0 (%95 GA 10-22) ay, B grubundamedyan 15Â±5.0 (%95 GA 5-25) aydı. Gruplar arasında progresyonsuz sağ kalım vegenel sağ kalım açısından istatistiksel olarak anlamlı fark yoktu. Grade 3-4 yan etkiaçısından değerlendirildiğinde A grubunda diyare 7 hastada (%50), mukozit 4hastada (%28.6) ve nötropeni 6 hastada (%42.9) görülürken, B grubunda diyare 4hastada (%25), mukozit 5 hastada (%31) görüldü. B grubunda grade 3-4 nötropenigözlenmedi. Tedaviye bağlı ölüm görülmedi.Sonuç: Her iki tedavi protokolü metastatik kolorektal kanserli hastalarda birinci sıratedavide etkili bulundu. Cevap oranı infüzyon 5-FU/FA grubunda daha yüksekti,ancak istatistiksel fark yoktu. Sağ kalım süreleri her iki grupta benzerdi. Buçalışmada metastatik kolorektal kanserli hastalarda birinci sıra tedavide uzuninfüzyon 5-FU/FA, iv bolus verilen 5-FU/FA'e eklenen irinotekan kadar etkilibulunmuştur. ki protokol de iyi tolere edildi. Tedaviye bağlı ölüm görülmedi.Nötropeni ve diyare irinotekan grubunda daha sıktı; bu protokol literatürle uyumluolarak daha toksik bulundu. Yan etkilerinden dolayı irinotekanın infüzyonel 5-FU/FA protokolleri ile birlikte kullanılması tercih edilebilir. nfüzyonel 5-FU/FAtoksisitesi düşük ve irinotekanlı bolus 5-FU/FA'ya eş değer etkinlikte ve düşükmaliyetli bir rejimdir.Anahtar Kelimeler: Metastatik kolorektal kanser, 5-fluorourasil, folinik asit,irinotekan.vi

Abstract:
ABSTRACTAim: Irinotecan is the first agent that makes survival advantage when added to 5-fluorouracil/folinic acid (5-FU/FA); which is the clasical treatment choice inmetastatic colorectal cancer. In this study we aimed to compare the effectivenes andside effects continuous infusion (22 hours) of 5-FU/FA with intravenous (IV) bolusinjection of 5-FU/FA plus irinotecan therapy. We wanted to demostrate thatcontinuous infusion of 5-FU/FA is more effective and has less toxic effects than 5-FU/FA plus irinotecan treatment.Patients And Methods: Thirty patients with metastatic colorectal cancer wereincluded in this study. In all patients colon or rectal cancer was showhistopathological and at least one metastatic lesion was shown by imaging methods.All patients were treated as first line for metastatic colorectal cancer. Thirty patientswere diveded in two groups. In first group (A) 5-FU 425 mg/m2/day for fiveconsecutive days as IV bolus, FA 20 mg/m2/day for five consecutive days as IVbolus and irinotecan (CPT-11) 180 mg/m2 first day as 90 minutes administrated inperiods of 28 days. In the second group (B) 5-FU 1000 mg/m2/day for fiveconsecutive days as 22 hours IV infusion and FA 100 mg/m2/day for five consecutivedays as 2 hours IV infusion in periods of 28 days. Response rate, benefit from thetreatment, survival rate and adverse effects were evaluated.Results: In this study 17 female (%56.7), 13 male (%43.3) totally 30 patients wereevaluated. Of 30 patients, 14 were recieved chemotherapy in the firs group (A) and16 patients in the second group (B). There were no difference between two groupsaccording to age, sex, performans status, patient?s number and count of appliedchemotherapy number. Totally 145 times chemotherapy was administered to 30patients. In the first group (A) median 5.5 (2-6) in the second group (B) median 6 (3-6) cure chemotherapy were given. In the first group complete response was in onepatient (%7.1), partial response was in one patient (%7.1) (objective response ratewas 14.3%), 4 patients (%28.6) were accepted as stable disease (benefit fromtreatment was %42.9). In the second group complete response was seen only in onepatient (%6.3), while 3 patients (%18.3) had partial reponses (objective response ratewas %25) 4 patients (%25) were accepted as stable disease (benefit from treatmentviiwas %50). Survival without progression was median 9Â±2 months (%95 CI 5-13) inthe first group (A), median 7Â±2 months (%95 CI 3-11) in the second group (B).Overall survival rate was median 16Â±3 (%95 CI 10-22) months in the first group (A),median 15Â±5 (%95 CI 5-25) months in the second group (B). There were nostatistical differences between two groups according to survival rate withoutprogression and overall survival rate. When assessed about grade 3-4 adverse effects,while diarrhea was seen in 7 patients (%50), mucositis was seen in 4 patients(%28.6) and neutropenia was seen in 6 patients (%42.9) in the first group (A), in thesecond group diarrhea was seen in 4 patients (%25), mucositis was seen in 5 patients(%31) . There wasn?t seen grade 3-4 neutropenia in the second group. There wasn?tany mortality due to treatment.Conclusion: Both chemotherapy protocoles were effective in the first line treatmentof metastatic colorectal cancer. Response rate was higher in the second group (5-FU/FA group) but there was no statistical significans difference between two groups.Survival rates were similar in both groups. In this study it was demostrated that IVcontinuous infusion of 5-FU/FA was as effective as IV bolus injection of 5-FU/FAplus irinotecan as the first line treatment in patients with metastatic colorectal cancer.Both two protocoles were well tolerated. There was no mortality due to treatment.Neutropenia and diarrhea were higher in the first group; this protocole was foundmuch toxic as it was reported in the literature. Because of the irinotecan should beadministrated with 5-FU/FA infusional chemotherapy. Infusional 5-FU/FA is costeffective, less toxic and as effective as irinotecan plus IV bolus 5-FU/FA therapy.Key Words: Metastatic colorectal cancer, 5-fluorouracil, folinic acid, irinotecan.viii