Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

Berk, Veli,Kaplan, Mehmet Ali,Tonyali, Onder,Buyukberber, Suleyman,Balakan, Ozan,Ozkan, Metin,Demirci, Umut,Ozturk, Turkan,Bilici, Ahmet,Tastekin, Didem,Ozdemir, Nuriye,Unal, Olcun Umit,Oflazoglu, Utk Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-${\beta}$) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. Materials and Methods: Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). Results: A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. Conclusions: This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Prognostic Factors for Overall Survival in Patients With Metastatic Colorectal Carcinoma Treated With Vascular Endothelial Growth Factor-Targeting Agents

Cetin, Bulent,Kaplan, Mehmet Ali,Berk, Veli,Ozturk, Selcuk Cemil,Benekli, Mustafa,Isikdogan, Abdurrahman,Ozkan, Metin,Coskun, Ugur,Buyukberber, Suleyman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.3

Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

Clinicopathologic Characteristics and Therapeutic Outcomes of Primary Gastrointestinal Non-Hodgkin's Lymphomas in Central Anatolia, in Turkey

Bulent Eser,Bunyamin Kaplan,Ali Unal,Ozlem Canoz,Fevzi Altuntas,H. Ismail. Sari,Ozlem Er,Metin Ozkan,Can Kucuk,Makbule Arar,Sebnem Gursoy,Mustafa Cetin 연세대학교의과대학 2006 Yonsei medical journal Vol.47 No.1

We carried out a retrospective analysis of 74 patients who were presented to our center with histopathological diagnosis of primary gastro-intestinal non-Hodgkin's lymphoma between 1990 and 2001. All patients have been staged according to Lugano Staging System. For histopathological classification, International Working Formulation was applied. The treatment choice concerning the surgical or non-surgical management was decided by the initially acting physician. Treatment modalities were compared using the parameters of age, sex, histopathological results, stage, and the site of disease. Of the 74 patients, 31 werefemale and 43 were male, with a median age of 49 years (range 15-80). The stomach was the most common primary site and was seenin 51 of 74 patients (68.9%). The intermediate and high grade lymphomas constituted 91.9% of the all cases. In a median follow-up of 29 months (range 2-128), 20 out of 74 patients died. There was a three year overall survival rate in 65.4% of all patients. The three year overall survival rate was better in stage I and II1 patients who were treated with surgery plus chemotherapy (+/-RT) than those treated with chemotherapy alone (93.7% vs. 55.6%, p 0.05). The stage and presence of B symptoms affected the disease free survival and overall survival significantly, but the histopathologic grade only affected the overall survival. On the basis of these results, we suggest that surgicalresection is necessary before chemotherapy in early stage (stage I and II1) patients with gastrointestinal non-Hodgkin's lymphomas because of the significant survival advantage it would bring to the patient.

Lack of Prognostic Value of Mean Corpuscular Volume with Capecitabine Therapy in Metastatic Breast Cancer

Bozkurt, Oktay,Berk, Veli,Kaplan, Muhammed Ali,Cetin, Bulent,Ozaslan, Ersin,Karaca, Halit,Inanc, Mevlude,Duran, Ayse Ocak,Ozkan, Metin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ${\geq}100$ fl was considered as macrocytosis. Capecitabine was given at a dose of $2500mg/m^2$ daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ${\Delta}MCV$ level (post-treatment values at sixth week - baseline) was 6.4. Whilst ${\Delta}MCV$ was ${\geq}6.4$ in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ${\Delta}MCV$ ${\geq}6.4$ and in 30 (75%) of 40 patients with ${\Delta}MCV$ <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ${\Delta}MCV$ ${\geq}6.4$ and the group with ${\Delta}MCV$ <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.

Efficacy and Safety of Raltitrexed Combinations with Uracil-Tegafur or Mitomycin C as Salvage Treatment in Advanced Colorectal Cancer Patients: A Multicenter Study of Anatolian Society of Medical Oncology (ASMO)

Bozkurt, Oktay,Karaca, Halit,Ciltas, Aydin,Kaplan, M. Ali,Benekli, Mustafa,Sevinc, Alper,Demirci, Umut,Eren, Tulay,Kodaz, Hilmi,Isikdogan, Abdurrahman,Ozkan, Metin,Buyukberber, Suleyman Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: There is no standard treatment for patients with colorectal cancer (CRC) progressing after irinotecan and oxaliplatin treatment. Here we aimed to retrospectively evaluate the efficacy and tolerability of raltitrexed in combination with oral 5-fluoropyrimidine (uracil tegafur-UFT) or mitomycin C as salvage therapy in mCRC patients. Materials and Methods: A total of 62 patients who had received raltitrexed combined with UFT or mitomycin C were identified between December 2008 and June 2013. They were given raltitrexed 2.6 $mg/m^2$ (max 5 mg) i.v. on day 1 in combination with either oral UFT 500 mg/day on days 1-14 every 3 weeks (group A) or mitomycin C 6 $mg/m^2$ i.v. on day every 3 weeks (group B). Results: Forty-two patients (67.7%) were in group A and 20 (32.2%) in group B. In 15 patients (24%) grade 3/4 toxicity was observed, resulting in dose reduction, and in 13 patients (20.9%) dose delay was necessary. The median progression free survival (PFS) was 3 months (95%CI 2.65-3.34) and median overall survival (OS) was 6 months (95%CI 2.09-9.90) in the whole group. Median PFS was 3 months (95%CI 2.60-3.39) in group A vs 3 months (95%CI 1.64-4.35) in group B (p=0.90). Median OS was 6 months (95%CI 2.47-9.53) in group A vs 12 months (95%CI 2.83-21.1) in group B (p=0.46). Conclusions: The combination of raltitrexed with UFT or mitomycin C seem to be a salvage therapy option due to safety profile and moderate clinical activity in heavily-pretreated mCRC patients.

Collet-Sicard Syndrome Associated with Occipital Condyle Fracture and Epidural Hematoma

Fatih Serhat Erol,Cahide Topsakal,Metin Kaplan,Hanifi Yildirim,Mehmet Faik Ozveren 연세대학교의과대학 2007 Yonsei medical journal Vol.48 No.1

A 31-year-old male was presented with a very rare case of ipsilateral palsies of the nerves IX through XII (Collet-Sicard syndrome) after a closed head injury. An occipital condyle fracture that was associated with epidural hematoma was diagnosed by computed tomography. The patient was conservatively managed, and following the treatment, partial neurological recovery ensued. The phenomenon of occipital condyle fracture involving the last four cranial nerve palsies is relatively rare. Although 3 cases of Collet-Sicard syndrome that were caused by an occipital condyle fracture has been reported, the association between condyle fracture and epidural hematoma has never been described before.

Gemcitabine Plus Paclitaxel as Second-line Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

Baykara, Meltem,Coskun, Ugur,Berk, Veli,Ozkan, Metin,Kaplan, Muhammet Ali,Benekli, Mustafa,Karaca, Halit,Inanc, Mevlude,Isikdogan, Abdurrahman,Sevinc, Alper,Elkiran, Emin Tamer,Demirci, Umut,Buyukberb Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.10

Purpose: The aim of this retrospective study was to determine response rates, progression-free survival (PFS), overall survival (OS) and toxicity of gemcitabine and paclitaxel combinations with advanced or metastatic non-small cell lung cancer patients (NSCLC) who have progressive disease after platinum-based first-line chemotherapy. Methods: We retrospectively evaluated the file records of patients treated with gemcitabine plus paclitaxel in advanced or metastatic NSCLC cases in a second-line setting. The chemotherapy schedule was as follows: gemcitabine $1500mg/m^2$ and paclitaxel 150 mg/m2 administered every two weeks. Results: Forty-eight patients (45 male, 3 female) were evaluated; stage IIIB/IV 6/42; PS0, 8.3%, PS1, 72.9%, PS2, 18.8%; median age, 56 years old (range 38-76). Six (12.5%) patients showed a partial response (PR), 13 (27.1%) stable disease (SD), and 27 (56.3%) progressive disease (PD). The median OS was 6.63 months (95% CI 4.0-9.2); the median PFS was 2.7 months (95% CI 1.8-3.6). Grade 3 and 4 hematologic toxicities, including neutropenia (n=4, 8.4%), and anemia (n=3, 6.3%) were encountered, but no grade 3 or 4 thrombocytopenia. One patient developed febrile neutropenia. There were no interruption for reasons of toxicity and no exitus related to therapy. Conclusion: The combination of two-weekly gemcitabine plus paclitaxel was an effective and well-tolerated second-line chemotherapy regimen for advanced or metastatic NSCLC patients previously treated with platinum-containing chemotherapy. Although the most common and dose limiting toxicities were neutropenia and neuropathy, this regimen was tolerated well by the patients.