Oral Etoposide for Platinum-Resistant and Recurrent Epithelial Ovarian Cancer: a Study by the Anatolian Society of Medical Oncology

Kucukoner, Mehmet,Isikdogan, Abdurrahman,Yaman, Sebnem,Gumusay, Ozge,Unal, Olcun,Ulas, Arife,Elkiran, Emir T.,Kaplan, Muhammed A.,Ozdemir, Nuriye,Inal, Ali,Urakci, Zuhat,Buyukberber, Suleyman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Background: The aim of this study was to evaluate the efficacy and toxicity of long-term, low-dose oral etoposide as an advanced treatment option in patients with platinum resistant epithelial ovarian cancer. Materials and Methods: For the purposes of this study, 51 patients with histologically-confirmed, recurrent or metastatic platinum-resistant epithelial ovarian cancer (EOC) treated at six different centers between January 2006 and January 2011 were retrospectively evaluated. Patients were treated with oral etoposide (50 mg/day for a cycle of 14 days, repeated every 21 days). Results: Among the 51 platinum-resistant patients, 17.6% demonstrated a partial response and 25.5% a stable response. The median progression-free survival (PFS) was 3.9 months (95% CI, 2.1-5.7), while the median overall survival was 16.4 months (11.8.20.9). No significant relationship was observed between the pre-treatment CA 125 levels, post-treatment CA-125 levels and the treatment response rates (p=0.21). Among the 51 patients who were evaluated in terms of toxicity, grade 1 or 4 hematologic toxicity was observed in 19 (37.3%); and grade 1-4 gastrointestinal toxicity occurred in 15 patients (29.4%). Conclusions: Chronic low-dose oral etoposide treatment is generally effective and well-tolerated in platinum-resistant ovarian cancer patients.

Lack of Relation of Survivin Gene Expression with Survival and Surgical Prognostic Factors in Endometrial Carcinoma Patients

Aksoy, Rifat Taner,Thran, Ahmet Taner,Boran, Nurettin,Tokmak, Aytekin,Isikdogan, Betul Zuhal,Dogan, Mehmet,Thlunay, Hakki Gokhan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.16

Background: The relation ofsurvivin gene expression to survival and surgical prognostic factors in the patients with endometrial carcinoma is unclear. Materials and Methods: In this study, 62 cases who were operated due to endometrial carcinoma were investigated between 2003 and 2011 in the the gynecological oncology clinic of Female Disease Training and Investigation Hospital of Etlik Zubeyde, Hanim, Turkey. Clinical and surgical prognostic factors were investigated by screening the records of these cases. With the standard streptavidin-biotin immune peroxidase method, cytoplasmic and nuclear expression of survivin was investigated in sections with specific antibodies (1:100, diagnostic Bio Systems, USA) primer. The aim was to elucidate any relation between survivin expression and defined prognostic factors and survival. Results: There was no statistically significant relationship between cytoplasmic and nuclear indexes identified for survivin and age, body mass index, the levels of preoperative hemoglobin, platelet and Ca 125, stage, grade, lymph node meastasis, the number of meta statical lymph nodes (total, paraaortic and pelvic), myometrial invasion, serosal invasion, adnexal involvement, the presence of acid in the first diagnosis, the involvement of omentum, the adjuvant treatment application of the cases, the presence of recurrence and rate of mortality (p>0.05). Statistical significance was noted for the presence of advanced stage lymph node metastasis (pelvic, paraaortic, pelvic and paraaortic), serosal involvement, positive cytology, lymph vascular space invasion, intra abdominal metastasis, and omentum involvement. When investigated the relation between cytoplasmic and nuclear survivin indexes and total survival, the result was not statistically significant (p>0.05). Conclusions: In our study, there was no statistically significant relationship between the rates of cytoplasmic and nuclear survivin expression with identified prognostic factors and total or non-disease survival.

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.

Prognostic Factors for Second-line Treatment of Advanced Non-small-cell Lung Cancer: Retrospective Analysis at a Single Institution

Inal, Ali,Kaplan, M. Ali,Kucukoner, Mehmet,Urakci, Zuhat,Karakus, Abdullah,Isikdogan, Abdurrahman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Platinum-hased chemotherapy for advanced non-small cell lung cancer (NSCLC) is still considered the first choice, presenting a modest survival advantage. However, the patients eventually experience disease progression and require second-line therapy. While there are reliable predictors to identify patients receiving first-line chemotherapy, very little knowledge is available about the prognostic factors in patients who receive second-line treatments. The present study was therefore performed. Methods: We retrospectively reviewed 107 patients receiving second-line treatments from August 2002 to March 2012 in the Dicle University, School of Medicine, Department of Medical Oncology. Fourteen potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. Result: The results of univariate analysis for overall survival (OS) were identified to have prognostic significance: performance status (PS), stage, response to first-line chemotherapy response to second-line chemotherapy and number of metastasis. PS, diabetes mellitus (DM), response to first-line chemotherapy and response to second-line chemotherapy were identified to have prognostic significance for progression-free survival (PFS). Multivariate analysis showed that PS, response to first-line chemotherapy and response to second-line chemotherapy were considered independent prognostic factors for OS. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. Conclusion: In conclusion, PS, response to first and second-line chemotherapy were identified as important prognostic factors for OS in advanced NSCLC patients who were undergoing second-line palliative treatment. Furthermore, PS and response to second-line chemotherapy were considered independent prognostic factors for PFS. It may be concluded that these findings may facilitate pretreatment prediction of survival and can be used for selecting patients for the correct choice of treatment.

Accuracy of Frozen Sections for Intraoperative Diagnosis of Complex Atypical Endometrial Hyperplasia

Turan, Taner,Karadag, Burak,Karabuk, Emine,Tulunay, Gokhan,Ozgul, Nejat,Gultekin, Murat,Boran, Nurettin,Isikdogan, Zuhal,Kose, Mehmet Faruk Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.5

Objective: The purpose of this study was to correlate the histological diagnosis made during intraoperative frozen section (FS) examination of hysterectomy samples with complex atypical endometrial hyperplasia (CAEH) diagnosed with definitive paraffin block histology. Methods: FS pathology results of 125 patients with a preoperative biopsy showing CAEH were compared retrospectively with paraffin block pathology findings. Results: Paraffin block results were consistent with FS in 78 of 125 patients (62.4%). The FS sensitivity and specificity of detecting cancer were 81.1% and 97.9%, with negative and positive predictive values of 76.7%, and 98.4%, respectively. Paraffin block results were reported as endometrial cancer in 77 of 125 (61.6%) patients. Final pathology was endometrial cancer in 45.3% patients diagnosed at our center and 76.9% for patients who had their diagnosis at other clinics (p=0.018). Paraffin block results were consistent with FS in 62.4% of all cases Consistence was 98.4% in patients who had endometrial cancer in FS. Conclusion: FS does not exclude the possibility of endometrial cancer in patients with the preoperative diagnosis of CAEH. In addition, sufficient endometrial sampling is important for an accurate diagnosis.

Is Diabetes Mellitus a Prognostic Factor for Survival in Patients with Small Cell Lung Cancer?

Inal, Ali,Kaplan, M. Ali,Kucukoner, Mehmet,Urakci, Zuhat,Karakus, Abdullah,Nas, Necip,Guven, Mehmet,Isikdogan, Abdurrahman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.4

Background: Previous studies have pointed to many different prognostic factors for small cell lung cancer (SCLC) but diabetes mellitus (DM) has not been clearly or consistently identified as of prognostic value. The aim of this study was to investigate the prognostic significance of the characteristics of patients and clinical laboratory tests in SCLC. Specifically, we investigated that the impact of DM for survival in the patients receiving first-line etoposide plus cisplatin (EP) chemotherapy. Methods: We retrospectively reviewed 161 patients with SCLC with a focus on DM and other potential prognostic variables were chosen for univariate and multivariate analyses with respect to survival. Result: Among the sixteen variables of univariate analysis, five were identified to have prognostic significance: performance status (PS) (p<0.001), stage (p=0.001), DM (p=0.005), serum albumin (p<0.001) and hemoglobin levels (p=0.03). Multivariate analysis showed PS, stage and serum albumin level to be independent prognostic factors for survival (p=0.02, p=0.02 and p=0.009 respectively), but DM was not an independnet factor. Conclusion: In conclusion, PS, stage and serum albumin level were identified as important prognostic factors, while DM at the time of diagnosis of SCLC did not have prognostic importance for survival.

Significance of Hormone Receptor Status in Comparison of 18F -FDG-PET/CT and 99mTc-MDP Bone Scintigraphy for Evaluating Bone Metastases in Patients with Breast Cancer: Single Center Experience

Teke, Fatma,Teke, Memik,Inal, Ali,Kaplan, Muhammed Ali,Kucukoner, Mehmet,Aksu, Ramazan,Urakci, Zuhat,Tasdemir, Bekir,Isikdogan, Abdurrahman Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.1

Background: Fluorine-18 deoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) and bone scintigraphy (BS) are widely used for the detection of bone involvement. The optimal imaging modality for the detection of bone metastases in hormone receptor positive (+) and negative (-) groups of breast cancer remains ambiguous. Materials and Methods: Sixty-two patients with breast cancer, who had undergone both 18F-FDG-PET/CT and BS, being eventually diagnosed as having bone metastases, were enrolled in this study. Results: 18F-FDG-PET/CT had higher sensitivity and specificity than BS. Our data showed that 18F-FDGPET/CT had a sensitivity of 93.4% and a specificity of 99.4%, whiel for BS they were 84.5%, and 89.6% in the diagnosis of bone metastases. ${\kappa}$ statistics were calculated for 18F-FDGPET/CT and BS. The ${\kappa}$-value was 0.65 between 18F-FDG-PET/CT and BS in all patients. On the other hand, the ${\kappa}$-values were 0.70 in the hormone receptor (+) group, and 0.51 in hormone receptor (-) group. The ${\kappa}$-values suggested excellent agreement between all patient and hormone receptor (+) groups, while the ${\kappa}$-values suggested good agreement in the hormone receptor (-) group. Conclusions: The sensitivity and specificity for 18F-FDG-PET/CT were higher than BS in the screening of metastatic bone lesions in all patients. Similarly 18F-FDG-PET/CT had higher sensitivity and specificity in hormone receptor (+) and (-) groups.

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.

Prognostic Factors in First-Line Chemotherapy Treated Metastatic Gastric Cancer Patients: A Retrospective Study

Inal, Ali,Kaplan, M. Ali,Kucukoner, Mehmet,Urakci, Zuhat,Guven, Mehmet,Nas, Necip,Yunce, Muharrem,Isikdogan, Abdurrahman Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Background: The majority of patients with gastric cancer in developing countries present with advanced disease. Systemic chemotherapy therefore has limited impact on overall survival. Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyze prognostic factors for survival in advanced gastric cancer patients undergoing first-line palliative chemotherapy. Methods: We retrospectively reviewed 107 locally advanced or metastatic gastric cancer patients who were treated with docetaxel and cisplatin plus fluorouracil (DCF) as first-line treatment between June 2007 and August 2011. Twenty-eight potential prognostic variables were chosen for univariate and multivariate analyses. Results: Among the 28 variables of univariate analysis, nine variables were identified to have prognostic significance: performance status, histology, location of primary tumor, lung metastasis, peritoneum metastasis, ascites, hemoglobin, albumin, weight loss and bone metastasis. Multivariate analysis by Cox proportional hazard model, including nine prognostic significance factors evident in univariate analysis, revealed weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level to be independent variables. Conclusion: Performance status, weight loss, histology, peritoneum metastasis, ascites and serum hemoglobin level were identified as important prognostic factors in advanced gastric cancer patients. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for treatment.

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.