Yaşlı metastatik mide kanserli hastalarda tek başına oral kapesitabin ile platin kombinasyonlarının karşılaştırılması

Öz

Amaç: Mide kanseri, kanser kaynaklı ölümlerin önemli bir kısmını oluşturmaktadır. Tüm mide kanseri olgularının yarısından fazlası 70 yaş üzerinde olmasına rağmen yaşlı kanser hastalar kemoterapi etkinliğinin değerlendirildiği prospektif çalışmalarda kendilerine yer bulamamaktadırlar. Biz bu çalışmada iki onkoloji merkezindeki geriyatrik gastrik kanserli hastalarda kapesitabin bazlı kemoterapilerin etkinliğini ve uygulanabilirliğini araştırmayı amaçladık.

Materyal-metod:   Çalışmaya iki merkezden metastatik mide kanseri tanısı ile 2012- 2017 yılları arasında kemoterapi alan 65 yaş üzeri hastalar alındı. Hasta dosyaları retrospektif olarak değerlendirildi. Hastalar Amerikan Kanser Komitesi evrelendirme sistemi ve performans statusu Dünya Sağlık Örgütü skalasına göre değerlendirildi.

Bulgular: Çalışmaya alınan 81 hastada ortalama yaş 74 idi. Erkek cinsiyet ve adenokarsinom histolojik tip daha yüksek orandaydı. Hastaların çoğunluğuna kapesitabin-sisplatin kemoterapisi verilmişti. Hastaların ortalama takip süresi 42 aydır. Kapesitabin-sisplatin, kapesitabin-okzaliplatin, kapesitabin  kemoterapisi alan grupların median tüm sağ kalım sırasıyla 8 ay, 10,7 ay ve 8,9 ay olarak saptandı, arada istatistiksel fark bulunmadı (p=0,467). Tüm hastaların median tüm sağ kalım 8,7 bulundu. Kemoterapi alt grupları aralarındaki progresyonsuz sağ kalım farkı istatistiksel olarak anlamlı değildir (p=0,59). En sık yan etki anemi olarak saptandı. Grad 3-4 yan etkiler kollar arası benzerdi (p=0,725). Çok değişkenli analizde metastatik bölge sayısı ile mortalite riski istatistiksel anlamlı artış göstermiştir (p=0,001). Kemoterapi protokolleri ile mortalite riski arası ilişki yoktur (p=0,472). Kemoterapiden bağımsız olarak stomatit, bulantı-kusma, nöropati, nötropenik ateş ve nefrotoksisite yan etkileri mortalite riski ile istatistiksel anlamlı ilişki içindedir (sırasıyla p=0,045, p=0,047, p=0,036, p=0,02 ve p=0,049).

Sonuç: Çalışmamızda evre IV mide kanserli olgularda 8,7 ay tüm sağ kalıma ulaşılmıştır. Kemoterapi alt gruplarında ise hem yan etki hem de sağ kalımlar açısından anlamlı fark yoktur.  Stomatit, bulantı-kusma, nötropenik ateş, nefrotoksisite ve nöropati yan etkilerinin mortalite riskini arttırması, geriyatrik olgularda özellikle ağız bakımı, uygun antiemetik tedavi uygulanması, böbrek fonksiyon testlerininin sıkı takibi ve yeterli hidrasyon, enfeksiyon açısından koruyucu bariyer tedbirler ve nöropati ilişkili kronik hastalıkların etkin tedavisinin en az kemoterapi uygulanması kadar önem taşıdığını göstermiştir.  

Anahtar Kelimeler

• Mide kanseri,kapesitabin,yaşlı

Comparison of oral capecitabine alone versus platinum combinations in elderly metastatic gastric cancer patients

Öz

Background: Gastric cancer is responsible for a considerable proportion of all cancer-related deaths. Elderly cancer patients are often ignored in prospective studies in which the efficacy of chemotherapy is evaluated, although more than half of all gastric cancer cases are over the age of 70 years. The present study aims to evaluate the efficacy and feasibility of capecitabine-based chemotherapies in geriatric patients with gastric cancer.

Methods: A total of 81 patients over the age of 65 years who received chemotherapy for metastatic gastric cancer at two oncology centers between 2012 and 2017 were included in the study. The medical records of the patients were evaluated retrospectively, and the patients and their performance status were evaluated using the American Joint Committee on Cancer staging system and the World Health Organisation scale, respectively.

Results: The mean age was 74 years. The male gender and the adenocarcinoma histological type were seen in higher rates. Most of the patients underwent capecitabine-cisplatin chemotherapy, and the mean follow-up was 42 months. The median overall survival of the groups of patients receiving capecitabine-cisplatin, capecitabine-oxaliplatin and capecitabine was 8 months, 10.7 months and 8.9 months, respectively, indicating no statistically significant differences between the groups (p=0.467). The median overall survival of all patients was found to be 8.7. The progression-free survival between the different chemotherapy subgroups was not statistically significant (p=0.59). The most common side effect was found to be anemia. Grade 3–4 adverse effects were similar between the arms of the study (p=0.725). A statistically significant increase was found in the mortality risk with an increased number of metastatic sites in a multivariate analysis (p=0.001). No correlation was found between the chemotherapy protocols and mortality risk (p=0.472). Adverse effects such as stomatitis, nausea/vomiting, neuropathy, neutropenic fever and nephrotoxicity, independent of chemotherapy, were statistically and significantly associated with the mortality risk (p=0.045, p=0.047, p=0.036, p=0.02 and p=0.049, respectively).

Conclusions: Our study results show that adverse effects such as stomatitis, nausea/vomiting, neutropenic fever, nephrotoxicity and neuropathy increase the mortality risk which suggest that particularly oral health care, the application of appropriate antiemetic treatments, the close follow-up of kidney function tests and adequate hydration, protective infection barrier measures and effective treatment of neuropathy associated with chronic diseases are as important as chemotherapy in geriatric cases.

Anahtar Kelimeler

• Gastric cancer,capecitabine,elderly

Kaynakça

1. 1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30.
2. 2. Wils JA, Klein HO, Wagener DJ, Bleiberg H, Reis H, Korsten F, et al. Sequential high-dose methotrexate and fluorouracil combined with doxorubicin—a step ahead in the treatment of advanced gastric cancer: a trial of the European Organization for Research and Treatment of Cancer Gastrointestinal Tract Cooperative Group. J Clin Oncol. 1991 May;9(5):827-831.
3. 3. Kim NK, Park YS, Heo DS, Suh C, Kim SY, Park KC, et al. A phase III randomized study of 5-fluorouracil and cisplatin versus 5-fluorouracil, doxorubicin, and mitomycin C versus 5-fluorouracil alone in the treatment of advanced gastric cancer. Cancer. 1993 Jun 15;71(12):3813-3818.
4. 4. Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, et al. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-244.
5. 5. Kaufman PA, Awada A, Twelves C. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol 2015;33:594–601.
6. 6. Ishikawa T, Utoh M, Sawada N. Tumor selective delivery of 5-fluorouracil by capecitabine, a new oral fluoropyrimidine carbamate, in human cancer xenografts. Biochem Pharmacol 1998;55:1091–1097.
7. 7. Kim TY, Oh DY, Bang YJ. Capecitabine for the treatment of gastric cancer. Expert Rev Gastroenterol Hepatol. 2015;9(12):1471-1481.
8. 8. Ina K, Ina H, Yoneda M, Kabeya M, Yuasa S, Tomomatsu Y, et al. A retrospective analysis of chemotherapy for gastric cancer in later-stage elderly patients. Nihon Ronen Igakkai Zasshi. 2018;55(2):244-250.

9. 9. Trumper M, Ross PJ, Cunningham D, Norman AR, Hawkins R, Seymour M. Efficacy and tolerability of chemotherapy in elderly patients with advanced oesophago-gastric cancer: A pooled analysis of three clinical trials. Eur J Cancer. 2006; 42 : 827–834.
10. 10.Jatoi A, Foster NR, Egner JR, Burch PA, Stella PJ, Rubin J. Older versus younger patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and stomach: a pooled analysis of eight consecutive North Central Cancer Treatment Group (NCCTG) trials.. Int J Oncol. 2010; 36 : 601-606.
11. 11. Tan HL, Chia CS, Tan GHC, Choo SP, Tai DW, Chua CWL, et al. Metastatic gastric cancer: Does the site of metastasis make a difference? Asia Pac J Clin Oncol. 2019 Feb;15(1):10-17.
12. 12. Gasparini G, Inelmen EM, Enzi G, Santoro C, Sergi G, Cardin F, et al. Clinical and prognostic aspects of gastric carcinoma in the elderly. J Gastrointest Surg. 2006;10(3):395–401.
13. 13. Deans C, Yeo MS, Soe MY, Shabbir A, Ti TK, So JB. Cancer of the gastric cardia is rising in incidence in an Asian population and is associated with adverse outcome. World J Surg. 2011;35(3):617–624.