Publications by authors named "Mehmet Artac"

59 Publications

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab.

Int J Clin Oncol 2021 May 23. Epub 2021 May 23.

Medical Oncology, Istanbul Kartal Dr. Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey.

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.
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http://dx.doi.org/10.1007/s10147-021-01936-6DOI Listing
May 2021

A Phase II Study of the Combination of Oxaliplatin, Capecitabine, and Trastuzumab and Chemoradiotherapy in the Adjuvant Setting in Operated Patients With HER2-positive Gastric or Gastroesophageal Junction Cancer (TOXAG Study): A Turkish Oncology Group Study.

Am J Clin Oncol 2021 May 12. Epub 2021 May 12.

Department of Medical Oncology, Acibadem Adana Hospital Departments of Radiation Medical Oncology, Baskent University, Adana Department of Medical Oncology, Hacettepe University Department of Medical Oncology, Dr. A.Y. Ankara Oncology Training and Research Hospital Department of Medical Oncology, Gazi University Department of Medical Oncology, Medical Park Ankara Hospital Department of Medical Oncology, Ankara Yildirim Beyazit University, Ankara Department of Medical Oncology, Marmara University Department of Medical Oncology, Ethica Incirli Hospital Roche Pharmaceuticals Department of Medical Pharmacology, Bahcesehir University School of Medicine Department of Biostatistics and Medical Informatics, Koc University/MedStats Consulting, Istanbul Department of Medical Oncology, Necmettin Erbakan University Meram School of Medicine, Konya Department of Medical Oncology, Ege University, Izmir, Turkey.

Background: Trastuzumab prolonged the overall survival in patients with advanced gastric cancer with human epidermal growth factor receptor 2 (HER2) overexpression in combination with chemotherapy. In this phase II open-label prospective study, the tolerability and safety of trastuzumab with chemotherapy, and chemoradiotherapy for curatively resected patients with HER2-positive gastric carcinoma was investigated.

Methods: The patients with HER2-positive gastric, or gastroesophageal junction adenocarcinoma, after gastrectomy plus D2 dissection, were included. They received 3 cycles of oxaliplatin (100 mg/m2 intravenously day 1) plus capecitabine (850 mg/m2 orally days 1 to 14), trastuzumab (8 mg/kg intravenously day 1 in cycle 1, 6 mg/kg thereafter) every 21 days, followed by chemoradiotherapy. Trastuzumab was given for 1 year.

Results: Of the 212 patients screened, 35 were eligible, and 34 were treated. The median age was 56 years (minimum to maximum: 35 to 75 y), male patients constituted 73.5% (n=25), and 33 (97.1%) had gastric adenocarcinoma. R0 resection was performed in 30 (88.2%). The majority (26, 61.7%) were in stage III disease. Most of the adverse events were grade I/II, the most frequent grade III side effects were nausea (3, 8.8%), vomiting (3, 8.8%), diarrhea (2, 5.9%), and weight loss (n=2, 5.9%). Two patients died during the first 3 cycles of chemotherapy and chemoradiotherapy; 1 secondary to pulmonary thromboembolism, and the other due to cerebral ischemia. After excluding 2 with early progression and 1 consent withdrawal, of the remaining 31 patients, 28 (90.3%) were able to complete the chemotherapy and chemoradiotherapy part of the trial. After the 25 months follow-up period, 21 patients (61.8%) were alive. Overall survival at 12 and 24 months was 75.0% and 58.0%, while disease-free survival at 12 and 24 months was 65.7% and 55.0%, respectively.

Conclusions: Trastuzumab in combination with capecitabine, oxaliplatin following chemoradiotherapy as the adjuvant therapy for gastric or gastroesophageal junction adenocarcinoma was considered as safe and tolerable. The frequency of HER2 overexpression in curatively resected patients is comparable to that in patients with metastatic disease (trial registration: clinicaltrials.gov the identifier: NCT01748773, December 13, 2012, https://clinicaltrials.gov/ct2/show/NCT01748773).
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http://dx.doi.org/10.1097/COC.0000000000000825DOI Listing
May 2021

Pazopanib-associated secondary adrenal insufficiency in a patient with malignant solitary fibrous tumor.

J Oncol Pharm Pract 2021 May 12:10781552211016081. Epub 2021 May 12.

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, Turkey.

Introduction: Pazopanib is an agent that is being successfully used in soft tissue sarcomas. Some endocrine side effects may develop during pazopanib treatment. Here, we presented a case diagnosed with secondary adrenal insufficiency while being investigated for etiology of hypoglycemia which developed after pazopanib.

Case Report: A 69-year-old male patient was operated in June 2019 due to a lung mass 26 × 18 × 10 cm in size. Pathological diagnosis revealed a solitary fibrous tumor with malignant behavior. The patient received three lines of chemotherapy. After pazopanib treatment, a hypoglycemic attack was reported. Blood cortisol and ACTH (Adrenocorticotropic hormone) levels were not increased at the time of the hypoglycemic attack, and levels of other pituitary hormones were found to be normal. Electrolyte levels were in normal range. Since the counteracting hormone did not reach a sufficient level, it was considered secondary adrenal insufficiency. Hypoglycemic attacks did not occur during follow-up while taking steroid therapy and pazopanib.

Discussion: A single case of primary adrenal insufficiency has been reported in the literature. We here present a case who developed hypoglycemia after pazopanib and was diagnosed with drug-associated secondary adrenal insufficiency. When hypoglycemia develops during pazopanib treatment, we must be aware of adrenal insufficiency.
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http://dx.doi.org/10.1177/10781552211016081DOI Listing
May 2021

First renal metastasis report from tongue cancer.

Braz J Otorhinolaryngol 2021 Apr 8. Epub 2021 Apr 8.

Necmettin Erbakan University, School of Medicine, Department of Medical Oncology, Konya, Turkey.

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http://dx.doi.org/10.1016/j.bjorl.2021.03.007DOI Listing
April 2021

The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study.

J Gastrointest Cancer 2021 Mar 3. Epub 2021 Mar 3.

Department of Molecular Biology and Genetics, Faculty of Basic Sciences, Gebze Technical University, Kocaeli, Turkey.

Purpose: Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study.

Methods: Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed.

Results: Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045).

Conclusion: Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.
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http://dx.doi.org/10.1007/s12029-021-00602-4DOI Listing
March 2021

Vaginal metastasis in solid tumours: our four cases and review of the literature.

J Egypt Natl Canc Inst 2021 Feb 4;33(1). Epub 2021 Feb 4.

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Akyokuş, 42080, Konya, Turkey.

Background: Vaginal metastasis should be kept in mind when evaluating the staging tests of all cancers, especially endometrial cancer.

Case Presentation: We present four patients with vaginal recurrence who recently applied to our clinic. Three cases were of endometrial cancer and one case of rectal cancer. All patients presented with vaginal bleeding.

Conclusion: Standard treatment for vaginal metastasis has not yet been established. Therapeutic options for vaginal metastasis-separately or in combination-are surgical resection, radiotherapy, and chemotherapy.
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http://dx.doi.org/10.1186/s43046-021-00058-4DOI Listing
February 2021

Response to trastuzumab and investigation of expression profiles of matrix metalloproteinase-related proteins in primary breast cancer stem cells.

Clin Exp Med 2021 Jan 20. Epub 2021 Jan 20.

Meram Faculty of Medicine, Department of Medical Oncology, Necmettin Erbakan University, Konya, Turkey.

Breast cancer (BC) is the leading cause of cancer deaths in women. One of the reasons for the failure of BC treatment is reportedly the ineffectiveness of chemotherapeutic drugs against breast cancer stem-like cells (BCSCs). HER2 receptors have an important role in the self-renewal of BCSCs. Matrix metalloproteinase (MMP) and cytokine levels were found to be higher in BCSCs, which demonstrates their potential metastatic capacity. Therefore, the aim of this study was to evaluate the response of BCSCs to trastuzumab and to investigate the MMP levels in primary breast cancer cells and HER2 BCSCs. Tumour tissue samples were obtained during surgical intervention from ten breast cancer patients, and primary culture cells were established from these tissues. Four major molecular subgroups were sorted from the primary culture: HER2 BCSCs (CD44CD24HER2), HER2 BCSCs (CD44CD24HER2), HER2 primary culture cells (CD44CD24HER2) and triple positive primary culture cells (CD44CD24HER2). These cells were cultured and treated with trastuzumab, paclitaxel, carboplatin, and the combination of those three drugs for 96 h. Cellular responses to these drugs were determined by XTT cytotoxicity test. MMPs and cytokine array analysis showed that MMPs and TIMP-1, TIMP-2 proteins were expressed more in HER2 BCSCs than in primary culture. HER2 BCSCs were more resistant to drugs than HER2 BCSCs. Our findings suggest that the presence of HER2 BCSCs may be responsible for primary trastuzumab resistance in HER2 BC cell population. Further studies investigating the function of MMPs are needed for drug targeting of BCSCs.
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http://dx.doi.org/10.1007/s10238-021-00685-0DOI Listing
January 2021

Small bowel wall edema induced by regorafenib is associated with regorafenib intolerance and shorter survival in patients with metastatic colorectal cancer: A retrospective study.

J Oncol Pharm Pract 2020 Dec 6:1078155220978471. Epub 2020 Dec 6.

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, Turkey.

Introduction: Regorafenib, a receptor tyrosine kinase inhibitor, is a routinely used targeted agent in the current treatment of patients with refractory metastatic colorectal carcinoma (mCRC). The aims of this study were to detect the presence of bowel wall edema during regorafenib treatment via computed tomography (CT) and to assess the relationship between survival and regorafenib-induced bowel wall edema in patients with mCRC receiving regorafenib.

Patients And Methods: We retrospectively evaluated the presence of bowel wall edema on CT of 25 mCRC patients who received regorafenib and analyzed its relationship with progression free survival (PFS) and overall survival (OS).

Results: Among the 25 patients, 25 had small bowel wall edema (SBWE) and 14 had large bowel wall edema (LBWE) on at least one CT examination. The median SBWE value was 4.85 milimeters (mm). Of the 25 patients, 14 had SBWE ≤4.85 mm and 11 had SBWE >4.85 mm. Regorafenib intolerance was significantly higher at SBWE >4.85 mm patients (p = 0.03). The median PFS was 4.6 months (95% CI: 2.4-6.8) and median OS was 9.3 months (95% CI: 3.1-15.4). Median PFS and OS were shorter in patients with SBWE > 4.85 mm than in those with ≤4.85 mm, but not statistically significant (median PFS: 3.9 vs 4.6 months, p: 0.523; median OS: 5.6 vs 9.3 months, p: 0.977).

Conclusions: Regorafenib caused SBWE in patients with mCRC. Patients who developed more SBWE had a higher regorafenib intolerance and a shorter survival. Further studies are needed to confirm the predictor value of SBWE on the survival outcomes of patients with mCRC receiving regorafenib.
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http://dx.doi.org/10.1177/1078155220978471DOI Listing
December 2020

Tyrosine kinase inhibitors in the treatment of metastatic renal cell cancer patients with early cytokine intolerance: TURCOS, a Turkish national, prospective observational study.

J Oncol Pharm Pract 2020 Oct 13:1078155220963535. Epub 2020 Oct 13.

Department of Preventive Oncology, Hacettepe University Institute of Oncology, Ankara, Turkey.

Objective: Cytokines have been the mainstay of treatment in metastatic renal cell cancer (mRCC) for decades before the introduction of tyrosine kinase inhibitors (TKIs), which dramatically changed the therapeutic landscape in these patients. This observational study was designed to evaluate use of TKIs in the treatment of cytokine-intolerant mRCC patients.

Methods: A total of 151 cytokine-intolerant mRCC patients who were treated with TKIs (sunitinib, pazopanib and sorafenib) were enrolled in this prospective, non-interventional, multi-center observational study at 16 oncology centers across Turkey. Mean (SD) age was 61.3 (11.1) years and 74.8% were males. Data on duration of TKI treatment was the primary outcome measure. Additionally, overall response rate (ORR), progression free survival (PFS), overall survival (OS) and safety data were recorded.

Results: Median duration of treatment was 8.2 months at a median follow up of 17.9 months. ORR and disease control rate were 12.5% and 70.8%, respectively. Median PFS and OS were 7.5 months (95%CI: 6.4-10.4) and 27.3 months (95%CI: 17.6-27.3) with no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. The most common adverse events excluding progression-which was the protocol requirement were diarrhea (13.6%), asthenia (13.6%) and hand-foot syndrome (12.6%). Dose modifications were required in 30.5% of the patients and 15% discontinued TKIs because of toxicity.

Conclusions: Our findings confirm the efficacy and safety profile of TKIs in the first-line treatment of mRCC patients intolerant to cytokine treatment. There was no significant difference among three TKI agents in terms of treatment duration, ORR, PFS and OS. TURCOS ClinicalTrials.gov Identifier: NCT01585974. Registered April 25, 2012.
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http://dx.doi.org/10.1177/1078155220963535DOI Listing
October 2020

Programmed death-1 or programmed death ligand-1 inhibitors? A meta-analysis of differential efficacy as compared to chemotherapy in advanced non-small cell lung cancer.

J Oncol Pharm Pract 2021 Mar 12;27(2):405-413. Epub 2020 Oct 12.

Department of Medical Oncology, Medical Park Hospital, Gaziantep, Turkey.

Background: Programmed Death-1 (PD-1) and Programmed Death Ligand-1 (PDL-1) inhibitors have improved survival over chemotherapy in advanced Non- Small Cell Lung Cancer (NSCLC). However, it is unclear if there are class specific differences in the efficacy of Checkpoint Inhibitors (CPIs) in NSCLC, and this paper is designed to answer these clinical questions.

Methods: For this Meta-analysis, we searched PubMed, Science of Web, "Clinicaltrials.gov" and online sources for trials comparing PD-1 and PDL-1 CPIs in advanced NSCLC. The data for Hazard Ratio (HR) and their Confidence Intervals (CI) for Overall Survival (OS) was extracted.

Results: A sum of 9739 patients from 16 trials were included in the efficacy evaluation. For the OS endpoint, both PD-1 inhibitors (HR = 0.76, 95%CI = 0.69-0.83, P < 0.001) and PDL-1 inhibitors (HR = 0.84, 95%CI = 0.74-0.95, P < 0.001) were superior to chemotherapy in treatment naïve (upfront) patients, the results were similar in treatment refractory patients (PD-1 inhibitors (HR = 0.67, 95%CI = 0.60-0.75, P < 0.001) and PDL-1 inhibitors (HR = 0.78, 95%CI = 0.69-0.88, P < 0.001) were superior to chemotherapy). There was no difference in the effect of PD-1 and PDL-1 classes of CPIs over chemotherapy in treatment naïve and treatment refractory settings (Q = 1.88, df = 1, P = 0.017, and, Q = 3.27, df = 1, P = 0.070, respectively).

Conclusion: Efficacy of PD-1 and PDL-1 class of CPIs was not different, although differences among individual CPIs or their combinations cannot be excluded. We were also able to compute pooled efficacy data, as compared to chemotherapy alone, for trials where these groups of CPIs were utilized.
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http://dx.doi.org/10.1177/1078155220964903DOI Listing
March 2021

Pemetrexed-induced Sweet Syndrome: First case report in the medical literature.

J Oncol Pharm Pract 2020 Oct 7:1078155220963178. Epub 2020 Oct 7.

Department of Medical Oncology, Necmettin Erbakan University School of Medicine, Konya, Turkey.

Introduction: Sweet Syndrome, also known as acute febrile neutrophilic dermatosis, is a rare inflammatory disease characterized by the sudden emergence of painful, edematous, and erythematous papules, plaques, or nodules on the skin, which usually fully responsive to systemic corticosteroids. Skin lesions are often accompanied by fever and leukocytosis. Here we present a case of Sweet Syndrome caused by pemetrexed in metastatic lung adenocarcinoma.

Case Report: A 52-year-old patient with metastatic lung adenocarcinoma received multiple lines of chemotherapy. The patient presented with extensive skin lesions after performing of pemetrexed chemotherapy. He had a fever and elevations in blood levels of C-reactive protein (CRP), sedimentation, leucocytes, and neutrophils. Neutrophil predominant perivascular and interstitial dermatitis, focal micropustule formation, and severe neutrophilic dermatosis were reported in skin biopsy. Topical steroid and oral antihistamine treatment were started as initial treatment. Cutaneous side effects related to pemetrexed are often reported as 'skin rash,' which is a non-specific term. Therefore, the diagnosis of Sweet Syndrome must be confirmed by skin biopsy. It is essential to exclude the presence of an infection and medication history. Recovery in drug-induced Sweet Syndrome occurs after the drug that caused it was discontinued. Systemic corticosteroids are the first-line treatment for most cases.
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http://dx.doi.org/10.1177/1078155220963178DOI Listing
October 2020

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences.

Eur Urol Focus 2020 Sep 30. Epub 2020 Sep 30.

Medical Faculty, Ankara University, Ankara, Turkey.

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 treatment 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 metastatic urothelial cancer who progressed with first-line chemotherapy, consistent with the outcomes of the previous clinical trials in this setting.
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http://dx.doi.org/10.1016/j.euf.2020.09.010DOI Listing
September 2020

The preliminary effects of henna on chemotherapy-induced peripheral neuropathy in women receiving oxaliplatin-based treatment: A parallel-group, randomized, controlled pilot trial.

Eur J Oncol Nurs 2020 Oct 9;48:101827. Epub 2020 Sep 9.

Necmettin Erbakan University, Faculty of Medicine, Konya, Turkey. Electronic address:

Purpose: Chemotherapy-induced peripheral neuropathy (CIPN) may frequently occur in patients receiving oxaliplatin-based treatment. The aim of the present parallel-group, randomized, controlled pilot trial was to investigate the effect of henna on CIPN in women receiving oxaliplatin-based treatment.

Method: Sixty female patients receiving oxaliplatin-based treatment were randomly divided into two groups, i.e., one intervention group (n = 30) where henna was applied topically and one control group (n = 30) that received routine treatment and care. Women in the intervention group were provided a pack of henna prepared by the investigators following each treatment course (2nd, 3rd, and 4th courses) and were instructed to apply the henna on their palms, fingers, and soles. The chemotherapy-induced peripheral neuropathy assessment tool (CIPNAT) was completed by women subsequent to the 2nd (baseline), 3rd, and 4th courses of treatment.

Results: The intragroup assessment performed for the intervention group revealed that the total CIPNAT score significantly declined in the intervention group (p < 0.05). The score changes by time in the intervention and control groups were in favour of the intervention group, and the effect size for group × time interaction was η = 0.169. Similarly, regarding the symptoms intervention section of the tool, a positive change by time in the intervention group was observed, and the effect size concerning this change was large, i.e., η = 0.284.

Conclusions: The present study results showed that henna application on hands and feet has a beneficial effect on peripheral neuropathy. Applying henna is a promising approach in CIPN management.
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http://dx.doi.org/10.1016/j.ejon.2020.101827DOI Listing
October 2020

Checkpoint inhibitors in advanced nonsmall-cell lung cancer; a Bayesian network meta-analysis.

J Cancer Res Ther 2020 Jul-Sep;16(4):828-837

Department of Medical Oncology, Necmettin Erbakan University, Konya, Turkey.

Background: Checkpoint inhibitors (CPIs) have improved survival compared to chemotherapy alone in advanced nonsmall-cell lung cancer (NSCLC). This article aims to compare indirect evidence and rank the effect of different CPIs in this setting.

Materials And Methods: In this network meta-analysis, we searched for trials comparing CPIs in advanced NSCLC. Figures for survival endpoints were extracted. In addition, a network meta-regression analysis was carried out.

Results: A total of 9220 patients from 16 trials were included in the analysis. In the first-line setting, for the overall survival endpoint, the chemotherapy + Pembrolizumab combination had the highest effectivity rank probability as compared to chemotherapy (hazard ratio = 0.788, 95% credential interval = 0.728-0.855). For the second-line setting, and also for the efficacy in terms of progression-free survival, various CPIs and their combinations were ranked.

Conclusion: Some degree of differences in terms of efficacy exists between different types, dosages, settings, and combinations of CPI. We quantify these differences to guide clinical practice.
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http://dx.doi.org/10.4103/jcrt.JCRT_450_19DOI Listing
November 2020

The prognostic significance of the 18F-fluorodeoxyglucose positron emission tomography/computed tomography in early-stage nonsmall cell lung cancer.

J Cancer Res Ther 2020 Jul-Sep;16(4):816-821

Department of Medical Oncology, Necmettin Erbakan University Meram Medical Faculty, Konya, Turkey.

Context: The prognostic criteria for early-stage nonsmall cell lung cancer (NSCLC) wait to be explored.

Aim: In this study, our aim was to evaluate the prognostic significance of the positron emission tomography/computed tomography (PET/CT) maximum standardized uptake value (SUV) value of the primary tumor in patients with a diagnosis of early-stage NSCLC who received surgical treatment.

Settings And Design: This was a multicenter retrospective design.

Materials And Methods: Patients who had been diagnosed with early-stage NSCLC and who underwent surgery for the condition were included in this study. The preoperative fluorodeoxyglucose (18F-FDG) PET/CT results of the patients were retrospectively accessed from their medical files. The disease-free survival (DFS) rates of patients who had SUV values above and below the determined cutoff value were compared.

Statistical Analysis Used: SPSS version 22 and Kaplan-Meier method were used for statistical analysis.

Results: A total of 92 patients were included in the study. The median age of the patients was 60 years (range: 36-79). The determined cutoff SUV value of the primary tumor was 13.6. A comparison of the DFS rates of the patients with an SUV value above and below 13.6 revealed a significant difference in patients with Stage I (22.9 months vs. 50.3 months; P = 0.02) and Stage II (28 months vs. 40.4 months; P = 0.04), Stage I + II (43.5 months vs. 26.1 months; P = 0,02), and Stage IIIA (14.7 months vs. 13.6 months; P = 0.92) NSCLC.

Conclusions: We found that in early-stage NSCLC patients, the SUV value of the primary mass in 18F FDG PET/CT was a prognostic indicator for the DFS rates.
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http://dx.doi.org/10.4103/jcrt.JCRT_911_17DOI Listing
November 2020

The Real-Life Data of BRAF Mutation on the Treatment of Colorectal Cancer: a TOG Study.

J Gastrointest Cancer 2020 Sep 11. Epub 2020 Sep 11.

Meram Medicine Faculty, Department of Medical Oncology, Necmettin Erbakan University, Konya, Turkey.

Purpose: Colorectal cancer is the third leading diagnosis accounting for nearly 10% of all new cancers worldwide. The distinct features among BRAF mutant colorectal cancers make these tumor groups hard to treat for oncologists. The median overall survival (OS) of these types of cancers is reported to be 9 to 14 months.

Methods: The study was declared on the Turkish Oncology Study Group Conference and approved. The patients' data was received from the centers who confirmed to participate. The BRAF-mutated patients were included in the study. The demographic features (age, gender, etc.), type of mutation, tumor localizations, histology, microsatellite instability (MSI) status, metastasis patterns chemotherapeutic agents and progression, and death times were recorded.

Results: Thirty-nine patients were enrolled in the study. Sixteen patients had concurrent KRAS mutations, while 7 had NRAS mutations. Most of the patients received doublet chemotherapies in combination with anti-VEGF agents in the first and second line of the treatment. There was a significant difference in OS according to the stage which showed a decreased survival in stage IV patients at the time of diagnosis. Concurrent KRAS mutation resulted in increased OS. The median OS was 47 and 24 months favoring the KRAS mutant group. The patients whose primary tumor operated had better survival when compared with other patients. The median OS of the operated group was 47 months, while the non-operated group was 24 months. Liver metastasis was related to worse prognosis at the time of diagnosis in univariate analysis.

Conclusion: In our study we found a high concurrent RAS mutation ratio in a BRAF mutant patient group which was different from prior studies. The concurrent mutations resulted in a favorable outcome in terms of OS which is also different from the current knowledge. More prospective studies are needed especially BRAF-mutated patient population and especially with concurrent RAS mutations.
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http://dx.doi.org/10.1007/s12029-020-00514-9DOI Listing
September 2020

The real-life outcome of pazopanib in patients with advanced soft tissue sarcoma: A retrospective cross-sectional study of a Turkish cohort.

J Oncol Pharm Pract 2020 Oct 17;26(7):1657-1666. Epub 2020 Feb 17.

Department of Medical Oncology, Meram Medical Faculty, Necmettin Erbakan University, Konya, Turkey.

Introduction: 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 3.97 months, 11.40 months, 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.
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http://dx.doi.org/10.1177/1078155220904138DOI Listing
October 2020

The Prognostic Value of Serum Semaphorin3A and VEGF Levels in Patients with Metastatic Colorectal Cancer.

J Gastrointest Cancer 2020 Jun;51(2):491-497

Department of Internal Medicine and Medical Oncology, Necmettin Erbakan University Meram Faculty of Medicine, Saraykoy Akyokus Street, 42080, Konya, Turkey.

Purpose: Despite new treatment options in metastatic colorectal cancer (mCRC), new prognostic markers are still needed to determine optimal chemoregimen especially for anti-angiogenesis drugs. In this study, we evaluated the serum semaphorin and VEGF-A levels as prognostic factors in patients with mCRC.

Methods: Patients with diagnosed mCRC who were treated with first-line bevacizumab plus chemotherapy were included in the study. Venous blood samples of 37 patients with metastatic colon cancer were taken, and serum semaphorin 3A and VEGF-A levels were studied in pre-treatment and the 1st and third months after the treatment was initiated.

Results: Totally, 37 patients were enrolled in the study. The patients' mean age was 62 years. Twenty-eight (49%) of the patients were male, and 19 (51%) were female. Serum semaphorin3A (sema3A) levels of the patients were 5.4 ± 7.4 ng/ml before the treatment, 3.5 ± 3.3 ng/ml at the first month, and 3.5 ± 3.7 ng/ml at the third month. Serum VEGF-A levels were 27.7 ± 32.9 ng/l before the treatment, 23.1 ± 28.1 ng/l at the first month, and 28.9 ± 30.2 ng/l at the third month. There was no significant correlation between the survival and pre-treatment VEGF-A level (p = 0.064). Overall survival (OS) was statistically significantly higher in patients with pre-treatment semaphorin 3A levels below 5.4 ng/ml than higher than 5.4 ng/ml (10.5 months vs 4.5 months, respectively, HR 0.23, 95% CI 19.635-11,391, p = 0.012).

Conclusion: Pre-treatment semaphorin 3A level can be a prognostic marker for the mCRC patients who were treated with bevacizumab in patients with metastatic colorectal cancer.
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http://dx.doi.org/10.1007/s12029-019-00263-4DOI Listing
June 2020

Comparison of palonosetron and granisetron in triplet antiemetic therapy in nonmetastatic breast cancer patients receiving high emetogenic chemotherapy: a multicenter, prospective, and observational study.

Cancer Chemother Pharmacol 2019 06 8;83(6):1091-1097. Epub 2019 Apr 8.

Department of Medical Oncology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey.

Purpose: We aimed to investigate the efficacy of 0.25 mg dose of palonosetron and granisetron in triplet antiemetic prophylaxis in breast cancer patients receiving HEC.

Methods: Patients with nonmetastatic breast cancer who received HEC [doxorubicin or epirubicin plus cyclophosphamide (AC/EC)] were enrolled in the study. The prophylactic triplet antiemetic regimens were used according to the doctor's preference during the first cycle of HEC as intravenous dexamethasone and palonosetron 0.25 mg or granisetron 3 mg on day 1 as well as oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3).The primary endpoint was complete response rate (CR) on acute and delayed chemotherapy-induced nausea and vomiting (CINV), separately.

Results: A total of 118 female patients were included in the study. Patients received AC (83%), EC (3%), and dose-dense AC (14%) as adjuvant (88%) or neoadjuvant (12%). The majority of patients received palonosetron (59%) containing antiemetic treatment. The CR rate on acute and delayed vomiting was very high and not statistically different in both of the arms (acute 87% vs. 96%, p = 0.089; delayed 90% vs. 92%, p = 0.489), respectively. Nevertheless, the CR rate on either acute or delayed nausea was lower than vomiting (acute 51% vs. 51%; delayed 38% vs. 29%, p = 0.203; respectively).

Conclusions: This is the second study that compared a 0.25 mg dose of palonosetron with first-generation setron in triplet antiemetic prophylaxis in cancer patients receiving HEC. We could not find meaningful statistical differences between two arms, regarding CR rate on acute and delayed CINV.
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http://dx.doi.org/10.1007/s00280-019-03831-4DOI Listing
June 2019

Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study.

Surg Oncol 2018 Sep 30;27(3):485-489. Epub 2018 May 30.

Department of Medical Oncology, NecmettinErbakan University, Meram Faculty of Medicine, Konya, Turkey. Electronic address:

Purpose: We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC).

Methods: We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens.

Results: The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients.

Conclusion: Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.
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http://dx.doi.org/10.1016/j.suronc.2018.05.032DOI Listing
September 2018

The relationship between nutritional status and handgrip strength in adult cancer patients: a cross-sectional study.

Support Care Cancer 2018 Jul 9;26(7):2441-2451. Epub 2018 Feb 9.

Faculty of Health Sciences, Department of Nutrition and Dietetics, Hacettepe University, 06100, Ankara, Turkey.

Purpose: Malnutrition is a common complication in head, neck and lung cancer patients, particularly in cases of gastrointestinal system (GIS) cancer. Therefore, an assessment of malnutrition is crucial for early nutritional interventions. It was conducted as a cross-sectional study to evaluate nutritional status of adult cancer patients.

Methods: The nutritional status of 104 cancer patients (52 GIS and 52 non-GIS cancer cases) using a Patient-Generated Subjective Global Assessment (PG-SGA), handgrip strength, certain anthropometric measurements and food consumption in and outside of the hospital were assessed.

Results: The percentages of malnutrition were 64.6 and 64.3% in the male patients with and without GIS cancer, respectively. They were 61.9 and 45.8% in the female patients with GIS and without GIS cancer, respectively. However, no significant difference was found between these two groups according to the malnutrition classification, PG-SGA score, handgrip strength and other anthropometric measurements (p > 0.05). The daily energy and protein intakes (per body weight) of the female patients in the hospital were significantly lower than those outside (p < 0.05). In addition, there was a positive moderate and significant relationship between the handgrip strength and lean body mass (r = 0.522, p = 0.000). A negative relationship was observed between the PG-SGA score and the handgrip strength (r = - 0.117, p = 0.071), but it was not statistically significant.

Conclusions: Cancer patients could be provided with nutritional education, and arrangements could be made with hospital nutritional services in order to prevent malnutrition.
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http://dx.doi.org/10.1007/s00520-018-4082-8DOI Listing
July 2018

Bevacuzimab May Be Less Effective in Obese Metastatic Colorectal Cancer Patients.

J Gastrointest Cancer 2019 Jun;50(2):214-220

Department of Medical Oncology, Anadolu Medical Center, Istanbul, Turkey.

Purpose: The purpose of this study was to investigate whether obesity affects survival in metastatic colorectal cancer (mCRC) patients treated with bevacizumab combined with chemotherapy.

Methods: A total of 563 patients with mCRC who had received first-line chemotherapy in combination with bevacizumab were studied. Patients were grouped as obese (BMI levels > 30) or non-obese (BMI levels < 30). Progression-free survival (PFS) and overall survival (OS) were analyzed. Primary tumor location was also investigated in terms of PFS and OS.

Results: The median age of the patients was 59 years. The non-obese group had longer PFS than the obese group (P = 0.030). The 2-year survival rate of the non-obese group was also significantly higher (P = 0.036). The median PFS of non-obese patients was significantly longer in Kras wild-type patients (10.1 vs. 8.1 months, P = 0.010). Among patients with left-sided primary tumor location, median PFS and OS were significantly higher in the non-obese group (PFS non-obese, 11.5 months; obese, 8.8 months; P = 0.002) (OS non-obese, 29.4 months; obese, 21.4 months; P = 0.026).

Conclusions: Efficacy of bevacizumab may be lower in obese patients. Among patients with Kras wild-type left-sided tumors treated with bevacizumab-based regimens, the prognosis could be worse for obese patients than that for non-obese patients. There is a need for prospectively designed studies of obese patients to prove the efficacy and dosages of bevacizumab in treatment of mCRC.
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http://dx.doi.org/10.1007/s12029-017-0047-2DOI Listing
June 2019

An update on the multimodality of localized rectal cancer.

Crit Rev Oncol Hematol 2016 Dec 26;108:23-32. Epub 2016 Oct 26.

Karmanos Cancer Center, Department of Gastrointestinal Oncology, Detroit, United States. Electronic address:

New strategies have reduced the local recurrence (LR) rate and extended the duration of overall survival (OS) in patients with localized rectal cancer (RC) in recent decades. The mainstay of curative treatment remains radical surgery; however, downsizing the tumor by neo-adjuvant chemo-radiotherapy and adjuvant cytotoxic therapy for systemic disease has shown significant additional benefit. The standardization of total mesorectal excision (TME), radiation treatment (RT) dose and fractionation, and optimal timing and sequencing of treatment modalities with the use of prolonged administration of fluoropyrimidine concurrent with RT have significantly decreased the rates of LR in locally advanced rectal cancer (LARC) patients. This review focuses on the optimization of multi-modality therapies in patients with localized RC.
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http://dx.doi.org/10.1016/j.critrevonc.2016.10.004DOI Listing
December 2016

Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

J Gastrointest Cancer 2017 Jun;48(2):176-180

Department of Medical Oncology, Akdeniz University Faculty of Medicine, Antalya, Turkey.

Purpose: Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev.

Methods: This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis.

Results: The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p = 0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus 13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022).

Conclusions: CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.
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http://dx.doi.org/10.1007/s12029-016-9879-4DOI Listing
June 2017

Changes in lifestyle upon diagnosis of cancer or other chronic illnesses: A Turkish Oncology Group study.

J Health Psychol 2018 03 22;23(4):561-566. Epub 2016 Jul 22.

7 Hacettepe University, Turkey.

Cancer, like other chronic illnesses, changes the patients' way of living significantly. Although some may think, for instance, that religiousness would increase with the diagnosis of cancer, no previous studies have been performed in the Turkish society to confirm this. We, as the Turkish Oncology Group, conducted a survey in seven different oncology centres, representing a large majority of Turkey, to investigate how patients' lifestyles changed following a cancer diagnosis; we used dialysis patients as a chronic illness control group. The study findings showed how changes in spiritual practices are completely in line with what is observed in other chronic illnesses. These findings may help to address cancer patients' needs and facilitate resource allocation accordingly.
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http://dx.doi.org/10.1177/1359105316658968DOI Listing
March 2018

Primary Tumor Resection and Survival in Patients with Stage IV Gastric Cancer.

J Gastric Cancer 2016 Jun 24;16(2):78-84. Epub 2016 Jun 24.

Department of Medical Oncology, Faculty of Medicine, Meram University, Konya, Turkey.

Purpose: The aim of this study was to determine whether surgical resection of the primary tumor contributes to survival in patients with metastatic gastric cancer.

Materials And Methods: A total of 288 patients with metastatic gastric cancer from the Akdeniz University, Antalya Training and Research Hospital, and the Meram University of Konya database were retrospectively analyzed. The effect of primary tumor resection on survival of patients with metastatic gastric cancer was investigated using the log-rank test. Kaplan-Meier survival estimates were calculated. Multivariate analysis was performed using Cox proportional hazards regression modeling.

Results: The median overall survival was 12.0 months (95% confidence intewrval [CI], 10.4~13.6 months) and 7.8 months (95% CI, 5.5~10.0 months) for patients with and without primary tumor resection, respectively (P<0.001). The median progression-free survival was 8.3 months (95% CI, 7.1~9.5 months) and 6.2 months (95% CI, 5.8~6.7 months) for patients with and without primary tumor resection, respectively (P=0.002).

Conclusions: Non-curative gastrectomy in patients with metastatic gastric cancer might increase their survival rate regardless of the occurrence of life-threatening tumor-related complications.
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http://dx.doi.org/10.5230/jgc.2016.16.2.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944006PMC
June 2016

Using Interferon Alfa Before Tyrosine Kinase Inhibitors May Increase Survival in Patients With Metastatic Renal Cell Carcinoma: A Turkish Oncology Group (TOG) Study.

Clin Genitourin Cancer 2016 08 2;14(4):e347-53. Epub 2016 May 2.

Department of Medical Oncology, Ankara University Medical Faculty, Ankara, Turkey.

Background: We aimed to investigate the outcomes of interferon alfa and sequencing tyrosine kinase inhibitors (TKIs) in patients with metastatic renal cell carcinoma.

Patients And Methods: This multicenter study assessing the efficacy of TKIs after interferon alfa therapy in the first-line setting in patients with metastatic renal cell carcinoma. Patients (n = 104) from 8 centers in Turkey, who had been treated with interferon alfa in the first-line setting, were included in the study. Prognostic factors were evaluated for progression-free survival (PFS).

Results: The median age of the patients was 57 years. The median PFS of the patients treated with interferon alfa in the first-line was 3.6 months. A total of 61 patients received TKIs (sunitinib, n = 58; sorafenib, n = 3) after progression while on interferon alfa. The median PFS among the TKI-treated patients was 13.2 months. In the univariate analysis for interferon alfa treatment, neutrophil and hemoglobin level, platelet count, and Karnofsky performance status were the significant factors associated with PFS. In the univariate analysis for TKI treatment, neutrophil and hemoglobin levels were the significant factors for PFS. The median total PFS of the patients who had been treated with first-line interferon alfa and second-line TKIs was 24.9 months.

Conclusion: This study showed that first-line interferon alfa treatment before TKIs may improve the total PFS in patients with metastatic renal cell carcinoma.
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http://dx.doi.org/10.1016/j.clgc.2016.04.021DOI Listing
August 2016

Benefit of Bevacizumab-Based Frontline Therapy in Patients with Metastatic Colorectal Cancer (mCRC): a Turkish Oncology Group Study.

J Gastrointest Cancer 2016 Sep;47(3):264-72

Department of Medical Oncology, Anadolu Medical Center, Istanbul, Turkey.

Background: Several chemotherapy regimens using bevacizumab have been developed. Our goal was to investigate regimens that have demonstrated significant clinical activity in patients with metastatic colorectal cancer (mCRC).

Materials And Methods: Six hundred and sixty six patients with mCRC who received first-line chemotherapy combination with bevacizumab were studied. Fluoropyrimidine (F) plus irinotecan (I)-based (FI-bev), F plus oxaliplatin (O)-based (FO-bev), and F-based (F-bev) treatment regimens were compared with respect to progression-free survival (PFS) and overall survival (OS).

Results: The median PFS of FI-bev (n = 414) was 10.9 months (95 % CI 10-11.8), of FO-bev (n = 211) was 9.4 months (95 % CI 8.3-10.4), and of F-bev (n = 41) was 9.5 months (95 % CI 5.9-13.1) (p = 0.089). The median OS of FI-bev was 26.3 months (95 % CI 21.7-30.9), of FO-bev was 27 months (95 % CI 24.3-29.7), and of F-bev was 23.3 months (95 % CI 12.7-33.9) (p = 0.102). In KRAS wild-type patients, the median PFS of FI-bev group was significantly longer than FO-bev group (10.5 vs. 9.1 months, p = 0.006). The FI-bev group had better OS than FO-bev group with borderline significance (p = 0.058). The FI-bev group had significantly longer OS than F-bev group. Patients who underwent metastasectomy or those with Eastern Cooperative Oncology Group performance status (ECOG-PS) ≤1 had longer PFS and OS independent of the type of chemotherapy regimen.

Conclusion: FI-bev may be the preferred frontline regimen for patients with KRAS wild-type mCRC. Metastasectomy and performance score were the strongest positive predictors of OS and PFS regardless of backbone chemotherapy regimen.
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http://dx.doi.org/10.1007/s12029-016-9823-7DOI Listing
September 2016

Prevalence of K-Ras mutations in hepatocellular carcinoma: A Turkish Oncology Group pilot study.

Mol Clin Oncol 2015 Nov 31;3(6):1275-1279. Epub 2015 Aug 31.

Department of Medical Oncology, Necmettin Erbakan University, Meram Faculty of Medicine, 42080 Konya, Turkey.

Hepatocellular carcinoma (HCC) is the fifth most common male-predominant type of cancer worldwide. There is no effective treatment regimen available for advanced-stage disease and chemotherapy is generally ineffective in these patients. The number of studies on the prevalence of K-Ras mutations in HCC patients is currently limited. A total of 58 patients from 6 comprehensive cancer centers in 4 metropolitan cities of Turkey were enrolled in this study. Each center committed to enroll approximately 10 random patients whose formalin-fixed paraffin-embedded tumor tissues were available for K-Ras, exon 2 genotyping. Two methods were applied based on the availability of adequate amounts of tumor DNA. In the first method, the samples were processed using TheraScreen. The genomic DNA was further used to detect the 7 most frequent somatic mutations (35G>A; 35G>C; 35G>T; 34G>A; 34G>C; 34G>T and 38G>A) in codons 12 and 13 in exon 2 of the K-Ras oncogene by quantitative polymerase chain reaction (PCR). In the second method, the genomic DNA was amplified by PCR using primers specific for K-Ras exon 2 with the GML SeqFinder Sequencing System's KRAS kit. The identified DNA sequence alterations were confirmed by sequencing both DNA strands in two independent experiments with forward and reverse primers. A total of 40 samples had adequate tumor tissue for the mutation analysis. A total of 33 (82.5%) of the investigated samples harbored no mutations in exon 2. All the mutations were identified via a direct sequencing technique, whereas none were identified by TheraScreen. In conclusion, in our patients, HCC exhibited a remarkably low (<20%) K-Ras mutation rate. Patients harboring K-Ras wild-type tumors may be good candidates for treatment with epidermal growth factor inhibitors, such as cetuximab.
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http://dx.doi.org/10.3892/mco.2015.633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665597PMC
November 2015

Metronomic oral chemotherapy with old agents in patients with heavily treated metastatic breast cancer.

J Cancer Res Ther 2015 Apr-Jun;11(2):287-90

Department of Medical Oncology, Akdeniz University, School of Medicine, Antalya, Turkey.

Background: We aimed to assess the efficacy of a metronomic regimen with cyclophosphamide and etoposide in heavily treated patients with metastatic breast cancer (MBC).

Materials And Methods: A total of 77 patients with MBC used continuous oral cyclophosphamide 50 mg/day and oral etoposide given as 2 × 50 mg/day for 2 days per week, were analyzed retrospectively from Akdeniz University and Selcuk University. The patients with MBC are predominantly refractory to antracyclines, taxanes, and antimetabolites.

Results: The patients were treated and followed between May 2005 and June 2014. The median progression-free and overall survival (PFS and OS) were 7.03 (5.06-8.99) and 32.5 (22.5-42.4) months, respectively. No prognostic factor was found for OS.

Conclusions: Metronomic treatment regimen with cyclophosphamide and etoposide is a novel and effective strategy in heavily pretreated MBC patients. This regimen can be used in early or late steps as independently from prognostic factors. Moreover, it has very low toxicity and is cheap. Impressive survival data and low cost may make this regimen a highly preferable option.
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http://dx.doi.org/10.4103/0973-1482.154008DOI Listing
April 2016