Second-Line Capecitabine and Oxaliplatin Combination for Gemcitabine-Resistant Advanced Pancreatic Cancer

Bayoglu, Ibrahim Vedat,Varol, Umut,Yildiz, Ibrahim,Muslu, Ugur,Alacacioglu, Ahmet,Kucukzeybek, Yuksel,Akyol, Murat,Demir, Lutfiye,Dirican, Ahmet,Cokmert, Suna,Yildiz, Yasar,Karabulut, Bulent,Uslu, Ruc Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17

Background: The role of second-line therapy in metastatic pancreatic cancer is not clear. In this study, we aimed to explore the second-line efficiency of capecitabine and oxaliplatin (XELOX) in patients with advanced pancreatic cancer who have received gemcitabine-based first-line therapy. Materials and Methods: We retrospectively evaluated 47 patients with locally advanced or metastatic pancreatic cancer previously treated with gemcitabine-based first-line regimens. Treatment consisted of oxaliplatin $130mg/m^2$ and capecitabine $1000mg/m^2$ twice daily with a 3 week interval, until unacceptable toxicity or disease progression. Results: Median number of cycles was 4 (range, 2-10). The overall disease control rate was 38.3%. The median overall survival and progression-free survival from the start of second-line therapy were 23 weeks (95%CI: 16.6-29.5 weeks) and 12 weeks (95%CI: 9.8-14.4 weeks), respectively. The most common grade 3-4 toxicities were nausea, vomiting and hematologic side effects. Conclusions: Our result suggests that the combination of capecitabine and oxaliplatin was tolerated with manageable toxicity and showed encouraging activity as second-line treatment of advanced or metastatic pancreatic cancer patients with ECOG performance status 0-2.

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

Uncu, Dogan,Bayoglu, Ibrahim Vedat,Arslan, Ulku Yalcintas,Kucukoner, Mehmet,Artac, Mehmet,Koca, Dogan,Oguz, Arzu,Demirci, Umut,Arpaci, Erkan,Dogan, Mutlu,Kucukzeybek, Yuksel,Turker, Ibrahim,Isikdogan, Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Multicenter Epidemiologic Study on Hepatocellular Carcinoma in Turkey

Can, Alper,Dogan, Erkan,Bayoglu, Ibrahim Vedat,Tatli, Ali Murat,Besiroglu, Mehmet,Kocer, Murat,Dulger, Ahmet Cumhur,Uyeturk, Ummugul,Kivrak, Derya,Orakci, Zuat,Bal, Oznur,Kacan, Turgut,Olmez, Sehmus,T Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Background: Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. Materials and Methods: Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. Results: Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. Conclusions: According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.

XELOX Plus Bevacizumab vs. FOLFIRI Plus Bevacizumab Treatment for First-line Chemotherapy in Metastatic Colon Cancer: a Retrospective Study of the Anatolian Society of Medical Oncology

Duran, Ayse Ocak,Karaca, Halit,Besiroglu, Mehmet,Bayoglu, Ibrahim Vedat,Menekse, Serkan,Yapici, Heves Surmeli,Yazilitas, Dogan,Bahceci, Aykut,Uysal, Mukremin,Sevinc, Alper,Hacibekiroglu, Ilhan,Aksoy, Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.23

Background: XELOX plus bevacizumab (XELOX-Bev) and FOLFIRI plus Bevacizumab (FOLFIRI - Bev) treatments are an effective strategies patients with metastatic colorectal cancer (mCRC).The aim of this study was to compare efficacy of first-line XELOX-Bev treatment vs FOLFIRI-Bev treatment for mCRC. Materials and Methods: A total of 409 patients with mCRC who received chemotherapy were included and divided into 2 groups. Group 1 (n=298) received XELOX-Bev and Group 2 (n=111) FOLFIRI-Bev. Comparisons were made in terms of overall (OS) and progression-free (PFS) survival, response rate (RR), and grade 3-4 toxicity. Results: Median follow-up was 11 months in Group 1 and 15 months for Group 2. Complete remission was observed in 29 (9.7%) and 2 (1.8%) patients, partial remission in 139 (46.6%) and 27 (24.5%), stable disease in 88 (29.5%) and 49 (44.1%) and progressive disease in 42 (14.1%) and 33 (30.0%) patients in Group 1 and 2, respectively. Median OS was 25 months (range 2-57 months, 95%CI; 22.2-27.7) for Group 1 and 20 months (range 1-67 months, 95%CI; 16.8-23.1) for Group 2 (p=0.036). Median PFS was 9.6 months (range 2-36 months, 95%CI; 8.8-10.4) for Group 1 and 9 months (range 1-44 months, 95%CI; 7.4-10.5) for Group 2 (p=0.019). Objective RR was 56.4% in Group 1 and 26.1% in Group 2 (p<0.001). Conclusions: First-line XELOX-Bev is more effective with a better response rate, prolongation of median PFS/OS, and a superior safety profile compared with FOLFIRI-Bev.

Original Article : Red Cell Distribution Width: A Novel Marker of Activity in Infl ammatory Bowel Disease

( Atakan Yesil ),( Ebubekir Senates ),( Ibrahim Vedat Bayoglu ),( Emrullah Duzgun Erdem ),( Refi K Demirtunc ),( Ayse Oya Kurdas Ovunc ) 대한간학회 2011 Gut and Liver Vol.5 No.4

Background/Aims: Studies concerning red cell distribution width (RDW) for use in the assessment of infl ammatory bowel disease (IBD) activity are limited. We investigated whether RDW is a marker of active disease in patients with IBD. Methods: In total, 61 patients with ulcerative colitis (UC) and 56 patients with Crohn`s disease (CD) were enrolled in the study group, and 44 age- and-sex-matched healthy volunteers were included as the control group. A CD activity index >150 in patients with CD indicated active disease. Patients with moderate and severe disease based on the Truelove-Witts criteria were considered to have active UC. In addition to RDW, serum C-reactive protein levels, erythrocyte sedimentation rates, and platelet counts were measured. Results: Twenty-nine (51.7%) patients with CD and 35 (57.4%) patients with UC had active disease. The RDW was significantly higher in patients with CD and UC than in controls (p<0.001 and p<0.001, respectively). A subgroup analysis indicated that for a RDW cut-off of 14%, the sensitivity for detecting active CD was 79%, and the specicity was 93% (area under curve [AUC], 0.935; p<0.001). RDW was the most sensitive and specifi c marker for active CD. However, it was not valid for UC, as the ESR at a cutoff of 15.5 mm/hr showed a sensitivity of 83% and a specicity of 76% (AUC, 0.817; p<0.001), whereas the RDW at a cutoff of 14% showed 17% sensitivity and 84% specicity for detecting active UC. Conclusions: RDW was elevated in IBD in comparison with healthy controls and increased markedly in active disease. RDW may be a sensitive and specifi c marker for determining active CD, whereas ESR is an important marker of active UC. (Gut Liver 2011;5:460-467)

Adjuvant Chemotherapy and Prognostic Factors in Stage II Colon Cancer - Izmir Oncology Group Study

Kucukzeybek, Yuksel,Dirican, Ahmet,Demir, Lutfiye,Yildirim, Serkan,Akyol, Murat,Yildiz, Yasar,Bayoglu, Ibrahim Vedat,Alacacioglu, Ahmet,Varol, Umut,Salman, Tarik,Yildiz, Ibrahim,Can, Huseyin,Tarhan, M Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach.

Second-Line Irinotecan after Cisplatin, Fluoropyrimidin and Docetaxel for Chemotherapy of Metastatic Gastric Cancer

Kucukzeybek, Yuksel,Dirican, Ahmet,Erten, Cigdem,Somali, Isil,Can, Alper,Demir, Lutfiye,Bayoglu, Ibrahim Vedat,Akyol, Murat,Medeni, Murat,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.6

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

Depression, Anxiety and Sexual Satisfaction in Breast Cancer Patients and their Partners-Izmir Oncology Group Study

Alacacioglu, Ahmet,Ulger, Eda,Varol, Umut,Yildiz, Ibrahim,Salman, Tarik,Bayoglu, Vedat,Dirican, Ahmet,Demir, Lutfiye,Akyol, Murat,Yildiz, Yasar,Kucukzeybek, Yuksel,Ataman, Gorkem,Can, Huseyin,Alacacio Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24

Background: We aimed to investigate anxiety, depression and sexual satisfaction levels and the effects of depression and anxiety upon the sexual satisfaction of Turkish breast cancer patients and their partners. Materials and Methods: Data were collected from one hundred breast cancer patients and their partners, using three forms: one covering information about socio-demographic characteristics of the patients, the Hospital Anxiety and Depression Scale (HADs) and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). Results: The frequencies, avoidance and touch subscores were statistically significantly high in the patients. Among those with high anxiety scores, the frequency, communication, satisfaction, touch, and anorgasmic subscale scores of GRISS were found to be significantly high. Among the partners whose anxiety scores were high, only the premature ejaculation subscale was statistically significant. It was determined that for partners with higher depression scores, the communication, satisfaction, avoidance, premature ejaculation and erectile dysfunction subscores of GRISS were statistically higher compared to partners with lower depression scores. Conclusions: Patients' quality of life may be increased by taking precautions to reduce their and their partners' psychosocial and psychosexual concerns.

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors?

Demir, Lutfiye,Ekinci, Nese,Erten, Cigdem,Kucukzeybek, Yuksel,Alacacioglu, Ahmet,Somali, Isil,Can, Alper,Dirican, Ahmet,Bayoglu, Vedat,Akyol, Murat,Cakalagaoglu, Fulya,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Background: To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). Materials and Methods: Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. Results: Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (${\geq}30%$) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ${\geq}10/50HPF$ mitotic activity/HPF was the only independent factor for risk of death in GIST patients. Conclusions: Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

Cisplatin Plus Gemcitabine for Treatment of Breast Cancer Patients with Brain Metastases: a Preferential Option for Triple Negative Patients?

Erten, Cigdem,Demir, Lutfiye,Somali, Isil,Alacacioglu, Ahmet,Kucukzeybek, Yuksel,Akyol, Murat,Can, Alper,Dirican, Ahmet,Bayoglu, Vedat,Tarhan, Mustafa Oktay Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.6

Background: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). Materials and Methods: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. Results: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second-line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). Conclusions: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.