Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

Prognostic value of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with epithelial ovarian cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have recently been evaluated in many cancers in prediction of survival outcomes. The purpose of this study was to investigate the impact of NLR and PLR on the prognosis of patients with epithelial ovarian cancer (EOC). MATERIALS AND METHODS: A total of 208 patients with EOC were included in the study. Hematological parameters and clinicopathological data during diagnosis were retrospectively evaluated. The cut-off values were determined by calculating receiver operating characteristic (ROC) curve analysis of the patients. RESULTS: The median over-all survival (OS) of patients with low NLR was 69 months (95% CI, 43.0-94.9) whereas high NLR was 36 months (95% CI, 29.1-42.8). The median OS with low PLR patients was 76 months (95% CI, 46.4-105.5) and high PLR was 35 months (95% CI, 28.5-41.4). In serous tumors (70.7%), the median OS with low NLR and high NLR was 54 months (95% CI, 27.9-80.0) and 34 months (95% CI, 28.2-39.7), and for the median OS with low PLR and high PLR it was 51 months (95% CI, 2 1.2-80.7) and 35 months (95% CI, 27.8-42.1), respectively. CONCLUSION: The present findings showed that the high NLR and high PLR were associated with poor prognosis and these values are significantly remarkable in EOC patients.

Leptin, insulin and body composition changes during adjuvant taxane based chemotherapy in patients with breast cancer, preliminary study.

BACKGROUND: The objectives of the present study were to compare the effect of adjuvant chemotherapy for breast cancer on serum insulin levels, serum leptin levels, and body composition in early stage breast cancer patients. MATERIALS AND METHODS: 17 breast cancer patients underwent 6 cycles of docetaxel (75 mg), epirubicine (100 mg) and cyclophosphamide (500 mg) (TEC). Anthropometrical and foot-to-foot body fat analyzer BIA, serum glucose, insulin, lipids, HOMA-IR and leptin were compared pre- and post-treatment. RESULTS: There was no statistically significant weight gain after treatment; however, there was an overall trend toward weight gain (69.7 ± 9.8 kg vs 71.03 ± 9.8; P= 0.05). From baseline to the end of the study, percentage of body fat and body fat mass showed an upward trend at the end of chemotherapy (1%; 2 kg P> 0.05). Pre and post-treatment period, leptin was strongly correlated with insulin and HOMA-IR (Spearman's pre-T; r = 0.74; P <0.001, r = 0.66; P = 0.004 post-T; r = 0.549; P =0.022, r = 0.51; P =0.036, respectively). Insulin levels were significantly increased in the post-treatment period (P < 0.05). On correlation analysis, post-T insulin levels were correlated with leptin, weight, fat-mass and fat percentage (Spearman's r = 0.549; P=.022, r = 0.567; P= 0.018, r = 0.498, P= 0.042, r = 0.502; P= 0.040, respectively). DISCUSSION: High insulin and leptin levels, important factors that were previously shown to be related to breast cancer outcome, and insulin resistance may be increased in taxane based chemotherapy regimen. These data may have broad implications for diet and lifestyle strategies for the prevention and treatment of cancers.

The relationship of insulin resistance and metabolic syndrome with known breast cancer prognostic factors in postmenopausal breast cancer patients.

PURPOSE: The aim of this study was to investigate the effect of metabolic syndrome and insulin resistance at the time of diagnosis on the known prognostic factors of breast cancer in postmenopausal breast cancer patients. METHODS: The study included 71 patients with a recent diagnosis of postmenopausal breast cancer, admitted at the Medical Oncology outpatient clinic of the Izmir Ataturk Training and Research Hospital between June 2010 and June 2011. We determined whether the patients had metabolic syndrome and insulin resistance at diagnosis, and recorded known prognostic factors, such as tumor size, axillary lymph node involvement, presence of distant metastasis, tumor grade, estrogen receptor (ER), progesterone receptor (PR), and CerbB-2 status. RESULTS: Among 71 patients, 25 (35%) had metabolic syndrome at the time of diagnosis, and 33 (46%) had insulin resistance with Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR)>2.7. No statistically significant difference was found in the prognostic values of breast cancer, i.e. tumor size, axillary lymph node involvement, distant metastasis, tumor grade, ER, PR, and CerbB-2 status between the patients with and without metabolic syndrome. There was no statistically significant difference in the prognostic factors of breast cancer at the time of diagnosis between 33 patients with insulin resistance and 38 patients without insulin resistance. CONCLUSION: Several previous studies showed a negative relationship between metabolic syndrome and insulin resistance and prognostic factors of breast cancer in postmenopausal breast cancer patients. However, our study failed to show such a relationship. The relationship between metabolic syndrome and insulin resistance and postmenopausal breast cancer was not well demonstrated due to the small number of patients, unknown duration of the metabolic syndrome and insulin resistance, and shorter follow-up period. Further studies are required to demonstrate the effect of metabolic syndrome and insulin resistance on the prognosis of breast cancer, including larger number of patients and longer follow-up periods.

Oxidative and antioxidative status after anthracyclinebased chemotherapy in breast cancer patients.

PURPOSE: The present study was undertaken to evaluate the effects of adjuvant anthracycline-based chemotherapy on thiobarbituric acid reactive substances (TBARS) and superoxide dismutase (SOD) levels in patients with breast cancer who had undergone surgery. METHODS: Body mass index (BMI), serum lipids (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), serum TBARS and SOD values were assessed in 30 patients with stage III breast cancer receiving adjuvant anthracycline- based chemotherapy. RESULTS: Anthracycline-based chemotherapy had no effect on BMI, blood pressure and lipid profile. A significant elevation was noted in TBARS (5.5±0.6 vs 5.9±0.9 µmol/L; p=0.038) and a significant reduction to baseline values in SOD levels (226.5±61.0 vs 203.1±48.3 U/mL; p=0.03) in patients following 6 cycles of adjuvant chemotherapy. CONCLUSION: The TBARS levels increased, whereas the SOD levels descreased after anthracycline-based chemotherapy. We suggest that oxidative stress is not always detrimental, as it can be beneficial in cancer treatment.

Depression and anxiety in cancer patients and their relatives.

PURPOSE: To investigate the depression and anxiety levels and the factors that affect patients receiving chemotherapy and their relatives with the Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) scoring system. METHODS: 330 patients and 330 relatives of these patients were enrolled in this study. The study forms including the questions regarding the patient demographic characteristics, BDI, and STAI were completed during face-to-face interviews by trained interviewers for the determination of the psychological status of the patients and their relatives. BDI and STAI were validated for Turkish population by studies made before. RESULTS: According to BDI scale, 96 (29.1%) patients had mild and 60 (18.2%) had severe depression. Seventy-one (21.5%) relatives had mild and 24 (7.3%) had severe depression. Anxiety evaluation was made by STAI scale and a statistical difference emerged between patients and relatives (patients: 44.93±8.8 vs relatives: 43.27±8.5, p=0.015). The depression and anxiety levels were higher in women, in people with low socio-economic level, in people having a time period between diagnosis and participation in the study longer than 6 months, and in people having relapsing disease. CONCLUSION: Since there are many emotional and psychological disorders in patients and their relatives, much attention should be paid in order to diagnose and treat their psychiatric disorders and enough information about their disease should be given.

The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma.

PURPOSE: Metastatic renal cell carcinoma (mRCC) bears a poor prognosis. We investigated the prognostic significance of some hematologic parameters of patients with mRCC. METHODS: We retrospectively reviewed the records of 53 patients with mRCC . The mean follow up time was 34 months (range 5-142).We assessed the prognostic value of hematologic parameters (leukocytes ,neutrophils, lymphocytes, platelets, neutrophil to lymphocyte ratio/NLR, platelet to lymphocyte ratio/PLR), and other clinical parameters with univariate and multivariate analysis. RESULTS: Memorial Sloan-Kettering Cancer Center (MSKCC) risk group , lung metastases, sunitinib treatment, lymphocyte count, NLR, and anemia significantly correlated with median overall survival (OS) on univariate analysis. The median OS in patients with a NLR < 3.4 was 32.2 months , significantly higher than the 13.9 months in patients with a ratio ≥ 3.4 (p = 0.006). Multivariate analysis revealed that MSKCC risk group and the NLR were independent predictors of OS. CONCLUSION: Hematologic parameters may be associated with OS in mRCC. However, further studies are needed to establish their routine use.

Quality of life of physicians and nurses working in an oncology clinic.

PURPOSE: The objective of this study was to determine possible differences in the perception of quality of life (QoL) between physicians and nurses working in an oncology clinic in Turkey. METHODS: Seventy-seven physicians and 67 nurses participated in this study. All participants provided information such as the working hours per day and the number of years working in an oncology clinic. The European Organization for Research and Treatment of Cancer (EORTC) QLQC30 questionnaire was used during face-to-face interviews by trained interviewers. RESULTS: The mean age of physicians and nurses were 32±0.8 and 29,9±0.9 years, respectively (p>0.05). Forty-four percent of physicians and all nurses were women. Fifty-three percent of physicians and 57% of nurses were single. Mean working hours per day and number of working years were similar between physicians and nurses. The physical, emotional, and cognitive function scales of physicians were better and statistically significant compared with nurses (p<0.0001, p<0.0006, and p<0.0127, respectively). Global health score was also better in physicians but without statistical significance. In physicians, a significant negative correlation with working hours and emotional, cognitive, role, and social function scales was found. A significant positive correlation with the number of working years and emotional function scale and also with age and role, emotional, cognitive, and social scales was found. Global health showed significant negative correlation with working hours, and positive correlation with age, number of working years, physical, role, emotional, cognitive, and social function scales. CONCLUSION: It is important to recognize that oncology workers, particularly nurses, have poor QoL. There are many factors adversely affecting the QoL of oncology workers in Turkey, therefore systems should be developed to provide better support and conditions for them.

Gemcitabine plus infusional 5-fluorouracil and high dose leucovorin in advanced stage pancreatic cancer.

PURPOSE: Advanced pancreatic cancer (APC) has a poor prognosis and chemotherapy remains the primary treatment modality. Gemcitabine (GEM) and 5-fluorouracil (5-FU) are the most active drugs in the treatment of pancreatic cancer. This study evaluated the efficacy and tolerability of the combination of these agents in APC. METHODS: Forty-four patients with APC were treated with GEM and infusional 5-FU with high dose leucovorin (LV5FU2) (GEMFUFOL regimen). RESULTS: A total of 240 chemotherapy cycles were administered. The overall response rate was 27.2%, and all responses were partial. Furthermore, disease stabilization was observed in 12 patients (27.2%). Median survival time and one-year survival rate were 9 months and 36.4%, respectively. The overall grade 3 or 4 adverse events were very low and mostly hematological. CONCLUSION: GEMFUFOL is still an active regimen for the treatment of APC and has an acceptable toxicity.

Taxane-based adjuvant chemotherapy reduces endothelin-1 and symmetric dimethylarginine levels in patients with breast cancer.

PURPOSE: To evaluate the levels of asymmetric dimethylarginine (ADMA), an endothelin and nitric oxide (NO) synthase inhibitor, in patients with node-positive breast cancer who had undergone surgery and in a control group including healthy individuals. The effects of taxane-based chemotherapy on endothelin-1 (ET-1) and ADMA levels in the patient group were also studied. METHODS: Body mass index (BMI), serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides), ADMA and ET-1 were studied in 19 healthy individuals and in 19 patients with stage II and III, lymph node-positive breast cancer receiving taxane-based chemotherapy. RESULTS: ET-1 (34.3±12.8 vs. 13.8±4.5 pg/mL; p<0.001) and ADMA (0.87±0.18 vs. 0.68±0.24 µmol/L; p=0.024) levels were significantly higher in the breast cancer group compared to the control group. A significant reduction was noted in ET-1 (34.3±12.8 vs. 27.3±4.3 pg/mL; p=0.021) and ADMA (0.87±0.18 vs. 0.73±0.15 µmol/L; p=0.014) levels in patients following 6 cycles of adjuvant chemotherapy to baseline values. CONCLUSION: The present study demonstrated significantly higher levels of ET-1 and ADMA in the breast cancer group compared to the control group, which were reduced significantly with adjuvant taxane-based chemotherapy. It is apparent that prospective studies are needed to understand the effect of reducing ET-1 and ADMA levels on patient survival. We believe that the present study will provide guidance to relevant future studies.

Impaired hypothalamo-pituitary-adrenal axis in patients with ankylosing spondylitis.

BACKGROUND: To investigate the hypothalamic-pituitary- adrenal (HPA) axis in patients with ankylosing spondylitis (AS) and healthy controls. METHODS: Forty-nine AS patients and 20 healthy controls were included. Lowdose ACTH test (LDST) was used to assess the HPA axis. Basal cortisol, stimulated peak cortisol levels, and acutephase reactants [C-reactive protein (CRP), erythrocyte sedimentation rate, and fibrinogen] were studied. Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index were also evaluated. RESULTS: Patient and control groups were not different regarding age, sex, body mass index and waist circumference (WC). Basal cortisol levels did not show a significant difference between groups. However, cortisol increment after low-dose ACTH was significantly impaired in AS subjects with respect to controls (20.0+/-4.4 vs 24+/-2.2 microg/dl, p<0.001). Eleven AS patients had impaired cortisol peak after LDST when a cortisol cut-off is accepted as 500 nmol/l (18 microg/dl) and none of the controls exhibited a peak cortisol responses to LDST<500 nmol/l. Comparison of AS subjects who were receiving anti-tumor necrosis factor (TNF) (no.=23), and conventional therapy (no.=26) yielded similar basal and peak cortisol concentrations. Peak cortisol concentrations were associated with basal cortisol, impaired cortisol response, CRP, and fibrinogen. Impaired cortisol response (subjects with peak cortisol levels <18 microg/dl) was significantly correlated with basal and peak cortisol concentrations and BASDAI. CONCLUSION: Our results indicate an increased prevalence of subclinical glucocorticoid deficiency in AS patients. Anti-TNF treatment seems not to have effect on HPA axis.

Efficacy and toxicity of lower dose UFT without leucovorin in metastatic gastric cancer patients.

PURPOSE: Gastric cancer is the 4th most commonly diagnosed cancer and the 2nd leading cause of cancer death worldwide. In this study assessed were the efficacy and toxicity of the combination of epirubicin, cisplatin and UFT in patients with metastatic gastric cancer (MGC). PATIENTS AND METHODS: In this retrospective study 27 patients with MGC were treated with epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) i.v. on day 1 and subsequently UFT 250 mg/m(2)/day orally in divided doses for 21 days, followed by a 7/day rest (EP/UFT). RESULTS: Response and toxicity evaluation was possible for 25 patients. Three complete (12%) and 2 partial (8%) responses were observed. With a median follow-up 37 weeks (range 15-117), the median progression-free survival (PFS) and overall survival (OS) were 24 and 31 weeks, respectively. WHO grade 3 or 4 toxicity included neutropenia in 3 (12%) patients and nausea/vomiting in 1 (4%) patient. Neutropenic fever developed in only 1 (4%) patient. CONCLUSION: EP-UFT with lower UFT doses and without leucovorin support is a safe and effective regimen as first -line treatment of MGC.

Complementary-alternative medicine among cancer patients in the western region of Turkey.

PURPOSE: To investigate the complementary/alternative medicine (CAM) applications and factors affecting its use among cancer patients in the western region of Turkey. PATIENTS AND METHODS: Face-to-face interview technique was used. Patients were asked to answer a questionnaire about their socio-demographic features, their level of knowledge about the disease and CAM application features. RESULTS: 220 adult cancer patients (79 male) were evaluated. Ninety-three (42.3%) were using at least one CAM method, the most common being herbal products which were preferred by 81 (36.3%) patients. Stinging nettle (Urtica dioica) was the most commonly used herbal product. Next was nutritional support, preferred by 45 (20.3%) patients. Eighty- nine (44.5%) of 200 patients who knew the diagnosis and 4 of 20 (20%) who did not were using CAM. In the patient group with awareness of the diagnosis, CAM application was significantly higher (p=0.034). CAM applications were detected in 34 of 70 (48.5%) patients with recurrent disease while 54 of 150 (36%) patients without recurrent disease were using CAM. The CAM applications were significantly higher in the group with recurrent disease (p=0.006). Fifty-three of 103 (51.4%) patients who had advanced disease were using CAM, while only 40 of 117 (34.1%) patients with local or locally advanced disease were using it. CAM applications were significantly higher in the group with advanced disease (p=0.030). Besides, knowing the diagnosis and disease recurrence were also independent risk factors for CAM usage [odds ratio (OR(: 3.1; 95% confidence interval (CI): 1.0-9.8 and OR: 2.2; 95% CI: 1.2-4.0 respectively]. As a result, nearly half of the patients (42.3%) in this region were using at least one of the CAM methods. CONCLUSION: The severity of the disease (recurrence and dissemination) and patients' awareness of the diagnosis were the most important factors affecting the CAM applications.

Hypoglycemia induced by long-acting somatostatin analogues in a patient with nonfunctional neuroendocrine tumor.

Somatostatin and its long-acting analogues are effective in symptom control in patients with functional neuroendocrine tumors; they are also able to control tumor growth. Somatostatin analogues are safe and generally well tolerated. In some cases they may cause serious complications. Somatostatin analogues are potent inhibitors of growth hormone (GH) and glucagon secretion. They cause impairment of hepatic glucose output and delay in intestinal absorption of carbohydrates. Patients with huge tumor mass and multiple liver metastases have increased risk of tumor-induced hypoglycemia. In these patients, long-acting octreotide may trigger serious hypoglycemia. The patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia. Herein, we present a patient with severe and prolonged hypoglycemia after long-acting octreotide treatment.

Synchronous appearance of male breast cancer and pancreatic cancer 15 years after the diagnosis of testicular cancer--report of a case.

The frequency of new neoplastic diseases among patients cured of testicular cancer is higher than in normal population. For these patients, synchronous occurrence of multiple neoplasms is not common. Also, less than 1% of all cases of breast cancer occur in males. We present herein a case having both breast and concurrent pancreatic cancer after being effectively treated for testicular cancer. To the best of our knowledge, this is the first case of synchronous breast and pancreatic cancer in a male patient following testicular cancer. Second cancer is the most severe long-term complication of chemotherapy or radiotherapy for patients with testicular cancer and the possibility of multiple cancers has to be taken into consideration when multiple lesions are present.

5-fluorouracil increases the number and complexity of premature complexes in the heart: a prospective study using ambulatory ECG monitoring.

The cardiac toxicity of LV5FU2 (de Gramont) regimen which is a widely used chemotherapy regimen in gastrointestinal system cancers is not well defined. We aimed to evaluate the impact of this regimen on cardiac rhythm. Two Holter ECG recordings were obtained in all patients with gastrointestinal system cancers treated with LV5FU2 regimen as first-line chemotherapy (one before and the second during the first 24 h of chemotherapy). Records were reviewed for the heart rate, rhythm, atrial premature complexes (APC), ventricular premature complexes (VPC), grades according to Lown-Wolf grading system and ST segment changes. Holter ECG recordings were evaluated in 27 patients. In the baseline evaluation, neither clinical symptom nor ST segment changes were observed. During the treatment period, chest pain was observed in two patients without any cardiac enzyme and ST segment changes. Moreover, a decrease in mean heart rate, and an increase in the number and complexity of premature complexes secondary to treatment were observed. The mean heart rate, APC per hour and VPC per hour (+/-SD) before vs. during treatment were, respectively, 93.1+/-16.4 vs. 81.6+/-12.7 (p=0.001), 18.9+/-54.0 vs. 45.3+/-53.8 vs. (p=0.049) and 12.7+/-29.6 vs. 38.1+/-42.1 (p=0.002). LV5FU2 regimen leads to a decrease in mean heart rate and a significant increase in APC and VPC which may lead to serious arrhythmias. These effects must be better understood for a safer administration of this useful and widely used drug regimen.