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    Addition of taxanes to combination chemotherapy in distal intestinal gastric cancer is more beneficial than proximal ones: A multicenter retrospective study of Turkish Oncology Group
    (Imprimatur Publications, 2019) Sedef, Ali Murat; Kose, Fatih; Sumbul, Ahmet Taner; Besen, Ali Ayberk; Hacioglu, Bekir; Gunaldi, Meral; Nayir, Erdinc
    Purpose: Advanced gastric cancer has a dismal prognosis. Platin/5-fluorouracil (PF) combination chemotherapy is the main treatment modality for metastatic gastric cancer patients. Third drug addition to PF is a controversial issue. The aim of this study was to evaluate the predictive role of tumor localization and histopathology on choosing three- or two-drug combination regimens. Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 516 patients with advanced gastric cancer has been treated at eight different oncology centers in Turkey between 2006 and 2016. Laboratory results and demographic data were collected and analyzed. Results: The median patient age was 59 years (range 25-85). Proximal intestinal and distal intestinal cancers were found in 357 (69.2 %) and 159 (30.8 %) patients, respectively. 5-fluorouracil (5FU) and cisplatin (PF) and cisplatin+5FU+docetaxel (PFtax, also known as DCF) were administered to 240 (46.5%) and 276 (53.5%) patients, respectively. Median progression free survival (PFS) was 5.0 (95% CI 4.21-5.29) and 8 months (95% CI 7.22-8.77)for PF and PFtax groups, respectively (p<0.01). When tumor localization was used as stratum in PFS survival, PFtax produced significantly higher PFS rates only in distal intestinal type gastric cancer compared to PF (p <0.01). Median overall survival (OS) was 12 (95% CI 9.8-14.2) and 16 months (95% CI 13.6-18.4)for the PF and PFtax groups, respectively (p=0.01). When tumor localization was used as stratum in OS, PFtax showed significantly higher OS rates only in the distal intestinal type gastric cancer compared to PF (p=0.01). Conclusion: Pathology and tumor location in gastric cancer may affect the outcome. Addition of taxanes as a third drug may significantly increase PFS and OS rates only in distal intestinal type gastric cancer but not in patients with proximal type gastric cancer.
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    Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.
    (Lippincott Williams & Wilkins, 2021) Tural, Deniz; Olmez, Omer Fatih; Sumbul, Ahmet Taner; Artac, Mehmet; Ozhan, Nail; Akar, Emre; Cakar, Burcu
    [Abstract Not Available]
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    Atezolizumab in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy: Results of real-life experience
    (Amer Soc Clinical Oncology, 2020) Tural, Deniz; Olmez, Omer Fatih; Sumbul, Ahmet Taner; Artac, Mehmet; Ozhan, Nail; Akar, Emre; Cakar, Burcu
    [Abstract Not Available]
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    Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences
    (Elsevier, 2021) Tural, Deniz; Olmez, Omer Fatih; Sumbul, Ahmet Taner; Artac, Mehmet; Ozhan, Nail; Akar, Emre; Cakar, Burcu
    Background: Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies in patients with locally advanced or metastatic platinum resistant urothelial carcinoma. Objective: To compare the real-life experience and data of clinical trials on ATZ treatment in metastatic urothelial carcinoma. Design, setting, and participants: Patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy from an expanded access program were retrospectively studied. Data of patients were obtained from their files and hospital records. Safety was evaluated for patients treated with at least one cycle of ATZ. Outcome measurements and statistical analysis: The primary endpoint was objective response rate (ORR). The secondary endpoints are overall survival (OS), progression-free survival (PFS), duration of response, and safety profile of patients. Kaplan-Meier methods were used to calculate median follow-up and estimate PFS and OS. Results and limitations: Data of 115 enrolled patients were analyzed. Most of the patients (92.3%, n = 106) had received chemotherapy regimen only once prior to ATZ. The median follow-up duration was 23.5 mo. The complete response rate, partial response rate, and ORR were 8.7% (n = 10), 20.0% (n = 23), and 28.7% (n = 33), respectively. The median duration of response was 20.4 mo (95% confidence interval [CI], 6.47-28.8). Of the 33 patients who responded to treatment, 60% (n = 20) had an ongoing response at the time of the analysis. PFS and OS with ATZ were 3.8 mo (95% CI, 2.25-5.49) and 9.8 mo (95% CI, 6.7-12.9), respectively. All-cause and any-grade adverse events were observed in 113 (98%) patients. Of the patients, 64% experienced a treatment-related adverse event of any grade and 24 (21.2%) had a grade 3-4 treatment-related adverse event. Limitations of the study included its retrospective design, and determination of treat-ment response based on clinical notes and local radiographic studies. Conclusions: In these real-life data, ATZ was effective and well tolerated in patients with metastatic urothelial carcinoma who have progressed with platinum-based first-line chemotherapy. ATZ is an effective and tolerable treatment for patients with locally advanced or metastatic platinum-resistant urothelial carcinoma in our study, similar to previously reported trials. Patient summary: Atezolizumab is effective and well-tolerated in patients with meta-static urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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    Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab
    (Springer Japan Kk, 2021) Tural, Deniz; Olmez, Omer Fatih; Sumbul, Ahmet Taner; Ozhan, Nail; Cakar, Burcu; Kostek, Osman; Ekenel, Meltem
    Background Atezolizumab (ATZ) has demonstrated antitumor activity and manageable safety in previous studies of patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of Atezolizumab was modest. In the current study, we evaluated the pretreatment prognostic factors for overall survival in patients with metastatic urothelial carcinoma who have progressed after first-line chemotherapy in the Expanded-Access Program of Atezolizumab. Patients and methods In this study, we present a retrospective analysis of 113 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of the patients was obtained from patient files and hospital records. Eligible patients included metastatic urothelial carcinoma patients treated with at least one course of ATZ. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p < 0.1), and then included a final model of p < 0.05. Results The median follow-up duration was 23.5 months. Of the patients, 98 (86.7%) were male and 13.3% were female. The median age was 65 years of age (37-86). In univariate analysis, primary tumor location in the upper tract, increasing absolute neutrophil count (ANC), increasing absolute lymphocyte count, neutrophil-to-lymphocyte ratio (NLR) > 3, liver metastases, baseline creatinine clearance less (GFR) than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 >=), and hemoglobin levels below 10 mg/dl were all the significantly associated with OS. Three of the five adverse prognostic factors according to the Bellmunt criteria were independent of short survival: liver metastases HR 3.105; 95% CI 1.673-5.761; p < (0.001), ECOG PS (1 >=) HR 2.184; 95% CI 1.120-4.256; p = 0.022, and Hemoglobin level below 10 mg/dl HR 2.680; 95% CI 1.558-4.608; p < (0.001). In addition, NLR > 3 hazard ratio [HR] 2.092; 95% CI 1.031-4.243; p = 0.041 and GFR less than 60 ml/min HR 1.829; 95% CI 1.1-3.041; p = 0.02, maintained a significant association with OS in multivariate analysis. Conclusions This model confirms the Bellmunt model with the addition of NLR > 3 and GFR less than 60 ml/min and can be associated with clinical trials that use immunotherapy in patients with bladder cancer.