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Öğe Bevacizumab every 4 weeks is as effective as every 2 weeks in combination with biweekly FOLFIRI in metastatic colorectal cancer(Springer, 2012) Yildiz, Ramazan; Benekli, Mustafa; Ozkan, Metin; Alkis, Necati; Berk, Veli; Kaplan, Mehmet Ali; Ciltas, AydinThe efficacy and tolerability of bevacizumab every 2 or 4 weeks using the same dosage in combination with biweekly FOLFIRI were retrospectively evaluated in metastatic colorectal cancer (mCRC) patients in the first-line and second-line therapy. A total of 332 patients from six centers were evaluated. The patients had received biweekly FOLFIRI in combination with bevacizumab 5 mg/kg every 2 weeks or every 4 weeks schedule for various reasons in individual patients. Approximately 70 % of all patients had 2-week treatment schedule. In the first-line therapy (n = 240), the overall response rate (ORR) was 34.1 % in 2-week and 36.3 % in 4-week groups. Median progression-free survival (PFS) was 8 months (95 %CI, 6.8-9.2) and 9 months (95 %CI, 6.6-11.4) (p = 0.074), and median overall survival (OS) was 22 months (95 %CI, 15.8-28.2) and 20 months (95 %CI, 8.1-31.9) (p = 0.612) in 2- and 4-week groups, respectively. One-year survival rate was 76.2 % for 2-week group and 73.2 % for 4-week group. In the second-line therapy (n = 92), the ORR was similar between the groups (24.5 vs 25.9 % in 2- and 4-week groups, respectively). Median PFS was 6 months (95 %CI, 4.7-7.3) and 11 months (95 %CI, 6.3-15.7) (p = 0.074), and median OS was 15 months (95 %CI, 9.6-20.4) and 17 months (95 %CI, 13.7-20.3) (p = 0.456) for 2-week and for 4-week groups, respectively. One-year survival rate was 61.3 % for 2-week and 71.3 % for 4-week groups. Toxicity profile was similar in 2- and 4-week groups and included neutropenia, febrile neutropenia, nausea and vomiting, diarrhea, mucositis, bleeding, hypertension, thromboembolism and fistulization. Bevacizumab 5 mg/kg every 2 weeks or every 4 weeks in combination with biweekly FOLFIRI had similar efficacy and tolerability in mCRC. Because of the retrospective nature of our study, the data should be examined cautiously. However, our study clearly points out the need for determination of optimum biological dosing interval of bevacizumab in well-designed, prospective, randomized trials.Öğe Biological Subtypes and Survival Outcomes in Breast Cancer Patients with Brain Metastases (Study of the Anatolian Society of Medical Oncology)(Karger, 2012) Kaplan, Muhammet Ali; Isikdogan, Abdurrahman; Koca, Dogan; Kucukoner, Mehmet; Gumusay, Ozge; Yildiz, Ramazan; Dayan, AdemBackground: The aim of this study is to determine the relationship between the survival outcomes and biological subtype in breast cancer patients with brain metastases. Methods: We retrospectively evaluated clinical data from 422 breast cancer patients with brain metastases between 2001 and 2011 from referral centers in Turkey. The study population was divided into four biological subtypes according to their hormone receptor status and HER2 expression. Results: Systemic treatment prolonged median overall survival (OS) after brain metastases in the entire group (14 vs. 3.2 months, p < 0.001). It also prolonged median OS after brain metastases in the triple negative (7.5 vs. 1.6 months, p = 0.010) and luminal A (14.3 vs. 7.1 months, p = 0.003) subgroups. The median OS for untreated patients, chemotherapy and/or hormonal therapy receiving patients, and chemotherapy and/or hormonal therapy plus targeted therapy receivers was 2, 5.8, and 17.7 months, respectively (p < 0.001), in the HER2-overexpressing subgroup. In the luminal B subgroup, it was 3.7, 5.3, and 15.4 months, respectively (p = 0.003). Conclusions: The use of systemic therapy improves OS after brain metastases in all biological subgroups. Targeted therapies also improve OS after brain metastases in HER2-positive patients. The combined use of targeted therapies and lapatinib are superior to single use and trastuzumab, respectively, in these patients. Copyright (C) 2012 S. Karger AG, BaselÖğe CHANGES IN NOVEL GASTROINTESTINAL AND RENAL INJURY MARKERS IN THE BLOOD PLASMA OF SHEEP FOLLOWING INCREASING INTRAVENOUS DOSES OF TOLFENAMIC ACID(Akademiai Kiado Zrt, 2019) Yildiz, Ramazan; Corum, Orhan; Atik, Orkun; Corum, Duygu Durna; Altan, Feray; Ok, Mahmut; Uney, KamilThe administration of high doses of non-steroidal anti-inflammatory drugs (NSAID), such as tolfenamic acid (TA), has undesirable effects on different organs. Some novel biomarkers have been reported that can determine the gastrointestinal and renal injury caused by a high dose of NSAIDs or other toxic substances. This study was aimed at determining the changes in gastrointestinal (TFF2 and HYP), renal (NGAL and KIM-1) and cardiac (cTn-I, CK-MB) injury markers after the use of increasing intravenous doses of TA in sheep. TA was administered intravenously to groups of six sheep each, at the dose levels of 0 (Group 0, i.e., G0), 2 (G2), 4 (G4), 8 (G8) and 16 (G16) mg/kg. The concentrations of the studied biomarkers were measured at 3, 9, 18 and 36 h after administration of TA. The TFF2 and NGAL concentrations in G16 were found to be significantly higher (P < 0.05) than in the other groups except for G8 at different sampling times. HYP concentration in G16 was observed to be significantly (P < 0.05) lower than that in all other groups at 36 h. KIM-1 level in G16 was significantly (P < 0.05) higher than in all other groups at different sampling times. An increase in the renal markers, KIM-1 and NGAL, in G8 was observed before any change in plasma creatinine and urea. The cardiac marker cTn-I in G16 was significantly (P < 0.05) higher than in other groups at different sampling times. The results showed that the novel biomarkers (HYP, TFF2, NGAL, and KIM-1) can be used to determine gastric and renal injury in sheep.Öğe The clinical and pathologic characteristics of 400 gastrointestinal stroinal tumor patients from Turkey: The final results of the Turkish Anatolian Society of Medical Oncology Multicenter Registery(Lippincott Williams & Wilkins, 2014) Sevinc, Alper; Seker, Mesut; Yildiz, Ramazan; Cihan, Sener; Kaplan, Mehmet Ali; Dane, Faysal; Karaca, Halit[Abstract Not Available]Öğe Clinical outcomes in patients who received lapatinib plus capecitabine combination therapy for HER2-positive breast cancer with brain metastasis and a comparison of survival with those who received trastuzumab-based therapy: a study by the Anatolian Society of Medical Oncology(Springer Japan Kk, 2014) Kaplan, Muhammet Ali; Isikdogan, Abdurrahman; Koca, Dogan; Kucukoner, Mehmet; Gumusay, Ozge; Yildiz, Ramazan; Dayan, AdemIn this study, we investigated the effect of lapatinib plus capecitabine treatment in HER2-positive breast cancer patients with brain metastasis. Of 405 metastatic breast cancer patients with brain metastases at referral centers in Turkey, 46 were treated with lapatinib plus capecitabine only after the development of brain metastasis. Patients who only received trastuzumab-based therapy after the development of brain metastases were accepted as the historic control group for survival analyses (n = 65). Patients who received both drugs consecutively or sequentially were excluded from the analyses (n = 34). Median age among 46 patients who received lapatinib plus capecitabine therapy was 45 years (27-76), and median time for development of brain metastases was 11.9 months (0-69 months). Twenty-six out of 38 patients who received lapatinib plus capecitabine and had extracranial metastasis showed partial response or stable diseases (68.4 %). Grade 3-4 toxicity was observed in eight patients (17.3 %). Median overall survival (OS) in patients treated with lapatinib plus capecitabine was significantly increased compared to that in patients treated with trastuzumab-based therapy (19.1 vs. 12 months, respectively, p = 0.039). The incidence of cerebral death was slightly decreased in patients who received lapatinib plus capecitabine compared to those who received trastuzumab-based therapy (32 vs. 43.4 %, p = 0.332). In the multivariate analysis, lapatinib plus capecitabine therapy remained an independent positive predictor for survival [odds ratio (OR), 0.57; p = 0.02]. Although this retrospective multicenter study had several limitations, the results suggest that undergoing lapatinib plus capecitabine therapy after the diagnosis of brain metastasis may further improve survival compared to undergoing only trastuzumab-based therapy.Öğe Ectopic Reticulum in a Cow(Univ Agriculture, Fac Veterinary Science, 2016) Altan, Semih; Koc, Yilmaz; Alkan, Fahrettin; Erol, Muharrem; Yildiz, RamazanA two years-old Holstein cow with poor appetite, reduced milk production, and partial defecation was evaluated in the present case report. After routine laboratory and clinical examinations, the animal further received ultrasound examination and then a right fossa paralumbal exploratory laparotomy was performed to the cow. The cow was diagnosed with ectopic reticulum on the laparotomy. After the content of the reticulum was removed, liquid paraffin was administered into the reticulum and its wall and abdominal wall was sutured as routinely. The prognosis of the animal deteriorated gradually following to the laparotomy and it was slaughtered by its owner. This is the first report showing the presence of an ectopic reticulum in a cow. (C) 2016 PVJ. All rights reservedÖğe The efficacy and safety of first-line and salvage therapies with bevacizumab combination chemotherapy regimens in metastatic colorectal cancer: A retrospective ASMO experience.(Lippincott Williams & Wilkins, 2013) Yildiz, Ramazan; Buyukberber, Suleyman; Koca, Dogan; Korai, Lokman; Ciltas, Aydin; Unal, Olcun Umit; Gumus, Mahmut[Abstract Not Available]Öğe Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third- or fourth-line treatment: A retrospective multicenter experience(Spandidos Publ Ltd, 2013) Kefeli, Umut; Benekli, Mustafa; Sevinc, Alper; Yildiz, Ramazan; Kaplan, Muhammed Ali; Ciltas, Aydin; Balakan, OzanSorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third-or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16-82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.Öğe Efficacy of Sunitinib in Turkish Patients with Gastrointestinal Stromal Tumors; Retrospective Multicenter Experience(H G E Update Medical Publishing S A, 2013) Kefeli, Umut; Buyukberber, Suleyman; Akyol, Murat; Yildiz, Ramazan; Kaplan, Muhammed Ali; Ciltas, Aydin; Sevinc, AlperBackground/Aims: Sunitinib is a multi-targeted thyrosine kinase receptor inhibitor used in patients with advanced gastrointestinal stromal tumours (GISTs). We evaluated the efficacy and tolerability of sunitinib therapy in Turkish patients with GISTs. Methodology: Between January 2001 and April 2012, 57 patients who had progressive disease or experienced unacceptable toxicity during imatinib treatment from multiple centers were investigated retrospectively. Results: Thirty-three patients were male and 24 were female. The median age was 55 years (range; 16-84 years). Thirty-eight of the patients received imatinib for longer than 12 months, 13 patients received for 6-12 months, and 6 patients received for less than 6 months. The clinical benefit of sunitinib was 73.7%. Treatment-related adverse events were reported in 78% of the patients. Adverse events were generally mild to moderate in intensity The median progression free survival (PFS) and overall survival (OS) of the patients that received sunitinib were 10.8 months and 23.9 months, respectively. The time of imatinib usage and response to sunitinib were independent prognostic factors for PFS and OS. Also, tumor size was an independent prognostic factor for PFS. Conclusions: Sunitinib is an effective treatment in Turkish patients with GISTs, with a clinical benefit of 73.7% and shows an acceptable tolerabilityÖğe Intravenous pharmacokinetics of moxifloxacin following simultaneous administration with flunixin meglumine or diclofenac in sheep(Wiley, 2020) Altan, Feray; Corum, Orhan; Yildiz, Ramazan; Faki, Hatice Eser; Ider, Merve; Ok, Mahmut; Uney, KamilIn this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co-administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 +/- 0.3 years and 53.5 +/- 5 kg of body weight) were used. A longitudinal design with a 15-day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co-administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high-performance liquid chromatography. The pharmacokinetic parameters were calculated using a two-compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half-life (t(1/2 beta)), total body clearance (Cl-T), volume of distribution at steady state (V-dss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h(-1) kg(-1), 1.66 L/kg and 8.91 hr*mu g/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t(1/2 beta) and AUC of moxifloxacin, they significantly reduced the Cl-T and V-dss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics.Öğe Lapatinib or trastuzumab? Which anti-HER2 treatment is more effective in the treatment of patients with HER2-positive breast cancer with brain metastases? An Anatolian Society of Medical Oncology Study(Amer Soc Clinical Oncology, 2012) Kaplan, Muhammet Ali; Isikdogan, Abdurrahman; Koca, Dogan; Kucukoner, Mehmet; Gumusay, Ozge; Yildiz, Ramazan; Oztop, Ilhan[Abstract Not Available]Öğe Long Term Survivors with Metastatic Pancreatic Cancer Treated with Gemcitabine Alone or Plus Cisplatin: a Retrospective Analysis of an Anatolian Society of Medical Oncology Multicenter Study(Asian Pacific Organization Cancer Prevention, 2012) Inal, Ali; Ciltas, Aydin; Yildiz, Ramazan; Berk, Veli; Kos, F. Tugba; Dane, Faysal; Unek, Ilkay TugbaBackground: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy has limited impact on overall survival (OS) so that eligible patients should be selected carefully. The aim of this study was to analyze prognostic factors for survival in Turkish advanced pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving gemcitabine (Gem) alone or gemcitabine plus cisplatin (GemCis). Methods: This retrospective evaluation was performed for patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and who received gemcitabine between December 2005 and August 2011. Twenty-seven potential prognostic variables were chosen for univariate and multivariate analyses to identify prognostic factors associated with survival. Results: Among the 27 variables in univariate analysis, three were identified to have prognostic significance: sex (p = 0.04), peritoneal dissemination (p = 0.02) and serum creatinine level (p = 0.05). Multivariate analysis by Cox proportional hazard model showed only peritoneal dissemination to be an independent prognostic factor for survival. Conclusion: In conclusion, peritoneal metastasis was identified as an important prognostic factor in metastatic pancreatic cancer patients who survived more than one year from the diagnosis of recurrent and/or metastatic disease and receiving Gem or GemCis. The findings should facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.Öğe Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves(Wiley, 2019) Corum, Orhan; Yildiz, Ramazan; Ider, Merve; Altan, Feray; Ok, Mahmut; Uney, KamilThe aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high-performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 1.85 and 3.31 hr, area under the plasma concentration-time curve (AUC(0-infinity)) 15.74 and 174 hr * mu g/ml, volume of distribution at steady-state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr(-1) kg(-1), respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 mu g/ml, time to reach peak concentration 1 and 1.5 hr, t(1/2 lambda z) 4.74 and 3.62 hr, and AUC(0-infinity) 22.75 and 147 hr * mu g/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12-hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of <= 0.5 and <= 4 mu g/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.Öğe Pharmacokinetics of enrofloxacin and danofloxacin in premature calves(Wiley, 2019) Corum, Orhan; Altan, Feray; Yildiz, Ramazan; Ider, Merve; Ok, Mahmut; Uney, KamilThe aim of this study was to determine the pharmacokinetics/pharmacodynamics of enrofloxacin (ENR) and danofloxacin (DNX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. The study was performed on twenty-four calves that were determined to be premature by anamnesis and general clinical examination. Premature calves were randomly divided into four groups (six premature calves/group) according to a parallel pharmacokinetic (PK) design as follows: ENR-IV (10 mg/kg, IV), ENR-IM (10 mg/kg, IM), DNX-IV (8 mg/kg, IV), and DNX-IM (8 mg/kg, IM). Plasma samples were collected for the determination of tested drugs by high-pressure liquid chromatography with UV detector and analyzed by noncompartmental methods. Mean PK parameters of ENR and DNX following IV administration were as follows: elimination half-life (t(1/2 lambda z)) 11.16 and 17.47 hr, area under the plasma concentration-time curve (AUC(0-48)) 139.75 and 38.90 hr*mu g/ml, and volume of distribution at steady-state 1.06 and 4.45 L/kg, respectively. Total body clearance of ENR and DNX was 0.07 and 0.18 L hr(-1) kg(-1), respectively. The PK parameters of ENR and DNX following IM injection were t(1/2 lambda z) 21.10 and 28.41 hr, AUC(0-48) 164.34 and 48.32 hr*mu g/ml, respectively. The bioavailability (F) of ENR and DNX was determined to be 118% and 124%, respectively. The mean AUC(0-48CPR)/AUC(0-48ENR) ratio was 0.20 and 0.16 after IV and IM administration, respectively, in premature calves. The results showed that ENR (10 mg/kg) and DNX (8 mg/kg) following IV and IM administration produced sufficient plasma concentration for AUC(0-24)/minimum inhibitory concentration (MIC) and maximum concentration (C-max)/MIC ratios for susceptible bacteria, with the MIC90 of 0.5 and 0.03 mu g/ml, respectively. These findings may be helpful in planning the dosage regimen for ENR and DNX, but there is a need for further study in naturally infected premature calves.Öğe Prognostic factors for gemcitabine-refractory patients with advanced pancreatic cancer: a retrospective analysis of a multicentre study (Anatolian Society of Medical Oncology)(Termedia Publishing House Ltd, 2015) Inal, Ali; Kos, F. Tuba; Algin, Efnan; Yildiz, Ramazan; Berk, Veli; Unek, Ilkay T.; Colak, DilsenAim of the study: Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of the study was to search for prognostic factors for survival in patients with gemcitabine (Gem)-refractory or with gemcitabine and cisplatin (GemCis)-refractory advanced pancreatic cancer. Material and methods: We retrospectively evaluated patients with Gem-or GemCis-refractory advanced pancreatic cancer. Sixteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Univariate and multivariate statistical methods were used to determine prognostic factors. Results: Multivariate analysis included the four prognostic significance factors in univariate analysis. Multivariate analysis showed that liver metastasis and second-line chemotherapy were considered independent prognostic factors for survival. Conclusions: Liver metastasis and second-line chemotherapy were identified as important prognostic factors in advanced pancreatic cancer patients refractory to treatment with Gem or GemCis. This prognostic factors may also facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.Öğe Prognostic Factors in Gastrointestinal Stromal Tumors: Multicenter Experience of 333 Cases from Turkey(H G E Update Medical Publishing S A, 2013) Seker, Mesut; Sevinc, Alper; Yildiz, Ramazan; Cihan, Sener; Kaplan, Mehmet Ali; Gokdurnali, Ayse; Dane, FaysalBackground/Aims: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. In an attempt to survey the approximate incidence, clinicopathological characteristics, and immunophenotypic features of GISTs in Turkey, we conducted a clinicopathological and immunohistochemical analysis of GISTs. Methodology: Three hundred and thirty-three patients with GIST from nine institutions in Turkey were retrospectively evaluated. Results: Between January 2001 and March 2011, a total of 333 patients with GISTs were included; of these, 204 (61.2%) were male and 129 (38.8%) were female. The median age was 55 years (range; 22402 years). At the median follow-up of 26 months (range; 4-166 months), the 1-, 3- and 5-year OS rates of the 333 patients were 96.9%, 85.8% and 78.5%, respectively. The 5-year DFS rate was 40%. The 5-year OS rate and median OS time for the patients with R-0 resection were significantly higher than for patients with metastatic diseases (79.7 vs. 75.7% and not reached vs. 115 months, respectively, p=0.04). Conclusion: Although our results should be confirmed by prospective studies, we believe that they contribute to the literature because the study included both resectable and metastatic or unresectable GIST patients and multicenter findings from Turkey.
