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Öğe The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?(2020) Kaplan, Muhammet Ali; Araz, Murat; Artaç, Mehmet; Sezgin, Yasin; Eryılmaz, Melek Karakurt; Karaağaç, MustafaObjectives: Pazopanib is an orally administered drug and has approval for the treatment of advanced Soft TissueSarcomas (aSTS). The absorption of pazopanib is pH-dependent. Acid-Reducing drugs such as proton pump inhibitors(PPI) may reduce the bioavailability of pazopanib. The primary purpose of this study was to assess whether the use ofconcomitant PPI and pazopanib had negative effects on survival outcomes.Methods: In this retrospective cross-sectional study, age ?18 years, having histologically proven STS, receiving pazopanibat least one day, and availability of information about the use of PPI during pazopanib treatment were the inclusioncriteria. Patients with adipocytic sarcoma were excluded.Results: A total of 46 eligible patients were assessed in this study. Thirty-one patients used concomitant PPI andpazopanib, 17 of them frequently used PPI, and the others occasionally. Fifteen patients never used concomitant PPI andpazopanib. The median progression-free survival (PFS) was 2.76 months, and the median overall survival (OS) was7.39?months for patients who never used concomitant PPI and pazopanib. Also, the median PFS was 5.22 months, and themedian OS was 14.52?months for patients who used concomitant PPI and pazopanib. In univariate analysis; usingconcomitant PPI (p=0.049) and primarily uterine located tumors (p=0.038) were significant parameters for PFS. Inmultivariate logistic regression analysis; both of using concomitant PPI (Wald=6.02; p=0.014) and primarily uterinelocated tumors (Wald=5.69; p=0.017) retained their association with longer PFS. No parameter was significant for OS.Conclusions: We showed that the use of concomitant PPI and pazopanib was associated with improved PFS. These resultsmay help guide clinicians and researchers for allowing patients co-administrating PPI and pazopanib, especially whentreating or investigating patients with dyspeptic symptoms.Öğe The prognostic role of HIF-1? and NF-?B expression in RAS wild-type metastatic colorectal cancer: A Turkish Oncology Group (TOG) study(Springer, 2023) Demirkiran, Aykut; Kilinc, Fahriye; Kocak, Mehmet Zahid; Demirkiran, Deniz; Korkmaz, Mustafa; Eryilmaz, Melek Karakurt; Araz, MuratBackground Not all RAS wild-type metastatic colorectal cancer (mCRC) patients experience the same benefit from anti-epidermal growth factor receptor (EGFR) treatments. Studies have shown that nuclear factor-kappa B (NF-kappa B), hypoxia-inducible factor-1 alpha (HIF-1 alpha), interleukin 8 (IL-8) and transforming growth factor beta (TGF-beta) may be therapeutic targets for mCRC. The aim of this study was to clarify the prognostic value of NF-kappa B, HIF-1 alpha, IL-8, and TGF-beta expression in patients with left-sided mCRC receiving EGFR inhibitors. Methods Patients with RAS wild-type, left-sided mCRC treated with anti-EGFR on the first line between September 2013 and April 2022 were included. Immunohistochemical staining for NF-kappa B, HIF-1 alpha, IL-8 and TGF-beta was performed from tumor tissues of 88 patients. Patients were divided into NF-kappa B, HIF-1 alpha, IL-8 and TGF-beta expression positive and negative group, moreover, expression positive group were also divided into two group as expression intensity low and high group. The median follow-up was 25.2 months. Results Median progression-free survival (PFS) was 8.1 (6-10.2) months in the cetuximab group, 11.3 (8.5-14) months in the panitumumab group (p = 0.09). Median overall survival (OS) was 23.9 (4.3-43.4) months in the cetuximab group, 26.9 (15.9-31.9) months in the panitumumab group (p = 0.8). Cytoplasmic NF-kappa B expression was present in all patients. The mOS was 19.8 (11-28.6) months in NF-kappa B expression intensity low group and 36.5 (20.1-52.8) months in high group (p = 0.03). The mOS of the HIF-1 alpha expression negative group was significantly longer compared with expression positive group (p = 0.014). There was no significant difference in IL-8 and TGF-beta expression status on mOS and mPFS (for all, p > 0.05). Positive expression of HIF-1 alpha was poor prognostic for mOS in the univariate analysis (HR:2.7, 95% CI 1.18-6.52, p = 0.02) and in multivariate analysis (HR 3.69, 95% CI 1.41-9.6, p = 0.008). High cytoplasmic expression intensity of NF-kappa B was found to have a good prognostic value for mOS (HR 0.47, 95% CI 0.26-0.85, p = 0.01). Conclusion High cytoplasmic expression intensity of NF-kappa B and negative expression of HIF-1 alpha could be a good prognostic marker for mOS in RAS wild-type left-sided mCRC.Öğe The prognostic value of lymph node ratio in patients with curatively resected pancreatic adenocarcinoma.(Amer Soc Clinical Oncology, 2015) Turan, Nedim; Araz, Murat; Algin, Efnan; Unal, Olcun Umit; Benekli, Mustafa; Tastekin, Didem; Dane, Faysal[Abstract Not Available]Öğe The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: A retrospective cross-sectional study of a Turkish cohort(Sage Publications Ltd, 2020) Karaagac, Mustafa; Sezgin, Yasin; Eryilmaz, Melek Karakurt; Araz, Murat; Kaplan, Muhammet Ali; Artac, MehmetIntroduction Soft tissue sarcomas are a heterogeneous and rare group of cancers with a short median overall survival despite the chemotherapy. Pazopanib has approval for the treatment of advanced soft tissue sarcoma. We aimed to investigate the clinical outcomes of Turkish patients with advanced soft tissue sarcoma who received pazopanib. Patients and methods This was a retrospective study. The inclusion criteria were: >= 18 years of age, having histologically proven advanced soft tissue sarcoma and receiving pazopanib at least one day. Results A total of 79 patients were assessed in this study. The median age was 49.6 years. The average dose intensity of pazopanib was 767 mg (400-800). The median duration of pazopanib treatment was 6.11 months. Fourteen patients (17.7%) used pazopanib at first line for advanced soft tissue sarcomas. The most common cause of discontinuation of pazopanib was the progression of the disease (89.6%). Pazopanib was well tolerated. The most common grade >= 3 side effect was anemia. The most common grade <= 2 side effects were anemia and hyperbilirubinemia. The median progression-free survival, overall survival, and follow-up were 3.97months, 11.40months, and 32.72 months, respectively. Female gender, good performance status, and the presence of pazopanib-induced hypothyroidism were associated with longer progression-free survival. Also, good performance status and being a responder to first-line treatment were associated with longer overall survival. Conclusions We showed that pazopanib was well tolerated and had clinical benefit in patients with advanced soft tissue sarcoma in a Turkish cohort. This is the first study that suggests pazopanib-induced hypothyroidism may act as a predictive marker for better outcomes in patients with advanced soft tissue sarcoma.
