The role of cardiac biomarkers as predictors of trastuzumab cardiotoxicity in patients with breast cancer.

AIM: Identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy. MATERIALS AND METHODS: Fifty-two women with HER2(+) breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken. RESULTS: The median age was 48.5 year (range: 26-74). Hypertension and obesity were two most common co-morbidities. The median duration application of trastuzumab was 52 weeks. During median 14.5 (3-33) months follow-up cardiac adverse events occurred in 5 (9.6%) patients and 2 out of 5 was grade III-IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0.004) and diabetes mellitus (p = 0.002) between patients with and without cardiotoxicity. CONCLUSION: Although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.

Phase II study of lapatinib in combination with vinorelbine in patients with HER2 positive recurrent or metastatic breast cancer: a multicentric Turkish Oncology Group (TOG) trial.

BACKGROUND: The aim of this explorative phase II study was to evaluate the activity and safety of lapatinib in combination with intravenous vinorelbine in women with HER2 positive metastatic or recurrent breast cancer. METHODS: Twenty-nine patients were enrolled. The primary objectives were response and clinical benefit (CB) rates, secondary objectives were toxicity, response duration and progression free survival. Patients received 1250 mg oral lapatinib continuously once daily and intravenous vinorelbine 20-25 mg/m(2) on days 1 and 8, every 3 weeks. RESULTS: Although 25 patients were evaluable for response, according to intend to treat analysis of 28 patients; 14% had confirmed partial response (PR) and 36% had stable disease more than 24 weeks with a CB rate of 50%. Sixty four percent of the patients suffered from grade 3-4 hematologic and 18% from grade 3 extra-hematologic toxicities. CONCLUSION: The results of this trial provide evidence to further investigate the potential of this combination for patients unsuitable for trastuzumab or who become refractory to trastuzumab.

Perception about influenza and pneumococcal vaccines and vaccination coverage among patients with malignancies and their family members.

PURPOSE: Although influenza and pneumococcal vaccinations for high-risk populations are recommended by current guidelines, vaccination coverage rate (VCR) is still low in patients with malignancies and the family members living with them. METHODS: During the 2011-2012 seasonal influenza (SI), we surveyed 359 patients with solid or hematological malignancies Data were recorded in an especially designed questionnaire after face to face interview. RESULTS: The median patient age was 57 years (range 18-90) and 177 (49.3%) patients were female. Overall vaccination rate was 17% and 4.2% for influenza and pneumococcus, respectively. VCR among family members was 21.2%. The most common causes for not getting vaccinated were lack of knowledge for indication by the patients (33.5%), getting chemotherapy (22.1%), fear of side effects (12.5%), lack of efficacy (12.1%), and not advised by the attending physician (5.9%). CONCLUSION: VCR was very low among patients with cancer and their family members. To eliminate misconceptions and improve vaccination coverage in this population, educational programs for patients and for physicians focusing on safety and efficacy of vaccine are needed.

Is obesity always a risk factor for all breast cancer patients? C-erbB2 expression is significantly lower in obese patients with early stage breast cancer

OBJECTIVES: The purpose of this study was to evaluate the relationship between body mass index and lipid profiles with breast cancer prognosis together with the relationship of these parametres with known breast cancer prognostic indices including c-erbB2 expression. PATIENTS AND METHODS: Four hundred and thirty-three patients diagnosed with breast cancer at Ankara University, Faculty of Medicine, Department of Medical Oncology made up the study population. The primary endpoints were relapse and death. Body mass index at the time of diagnosis, lipid levels at the time of diagnosis, estrogen receptor status, progesterone receptor status, c-erbB2 expression, tumor grade, patient age, axillary lymph node involvement level, tumor stage, menopausal status and surgery details were taken into account. RESULTS: The mean body mass indices were similar in the remission, relapse and mortality groups. Patients with body mass indices higher than 30 kg/m² had a lower incidence of c-erbB2 expression when compared to patients with body mass indices < 18.5 kg/m(2) (19 vs. 50 %, p = 0.009). Survival analysis revealed that patients with body mass indices < 18.5 kg/m(2) had significantly shorter disease free survivals when compared to patients with body mass indices between 25 and 29.9 kg/m(2). Mean serum lipid levels were similar in the remission, relapse and mortality groups. A trend toward relapse was shown in patients with total cholesterol > 240 mg/dl, but this was statistically insignificant. Survival analysis revealed that patients with triglyceride levels lower than 150 mg/dl had a statistically significant longer disease-free survival when compared to the other groups. Again a trend towards shorter overall survival was seen in patients with total cholesterol > 240 mg/dl, but this relationship was also statistically insignificant. CONCLUSION: Most large previous studies reported adverse breast cancer outcome with obesity. However in our study, patients with lower body weight had a shorter disease-free survival. This could be explained by the low number of patients in this study, genetic profile of the patient population, possible weight changes after treatment and the inverse relationship between body mass index and c-erbB2 expression (AU)

ABO and Rh blood groups frequency in women with HER2 positive breast cancer.

PURPOSE: The role of genetic factors in the development of cancer is widely accepted. Data on the role of ABO blood group and Rh factor in breast cancer is inconclusive. The aim of this study was to investigate the presence of a possible association between HER2 (+) breast cancer in Turkish women and ABO blood groups and Rh factor. METHODS: In 294 female patients with HER2 (+) breast cancer, ABO blood groups and Rh factor were examined. The relationship of blood groups with age, menopausal status, and family history of cancer, estrogen receptor (ER), progesterone receptor (PR) and HER2 status of these patients was evaluated. Blood groups distribution of 22,821 healthy blood donors was also assessed and compared with the patients' blood groups distribution. RESULTS: The median patient age was 47 years (range 20-80) and 56% of the patients were premenopausal. ER and PR were positive in 50 and 60% of the patients, respectively. Overall, the ABO blood group distribution of the 294 HER2 (+) breast cancer patients was similar to that of the healthy blood donors (p=0.36). Likewise there was no correlation between blood type and ER, PR and menopausal status. Rh (-) patients had more frequent family cancer history and this difference was significant for patients with blood group B Rh (-) and O Rh (-) (p = 0.04). CONCLUSION: In the present study we didn't find any relationship between HER2 status and ABO blood group and Rh factor. However, further studies with larger number of patients are needed to establish the role (if any) of blood groups in patients with breast cancer.

The symptomatic benefit (the clinical benefit response) from the second-line chemotherapy in patients with advanced gastric adenocarcinoma.

There are few reports on use of symptomatic benefits as an alternative or adjunctive for the assessment of objective response in chemotherapy of the advanced cancer. This study is performed to assess the symptomatic benefits (the clinical benefit response), in addition to the efficacy and toxicity of cisplatin plus infusional 5-fluorouracil (5-FU) combination as second-line therapy in patients with advanced gastric cancer. Fifty-eight advanced gastric cancer patients with previous chemotherapy were enrolled into the study. Cisplatin 20 mg/m(2) was given for 5 days, and 5-FU was given 1000 mg/m(2) as 20 h continuous infusion for 5 days, repeated every 28 days. The overall objective response rate was 11.3%, and overall tumour control rate was 33.9%. The clinical benefit response, in terms of weight gain, reduction in analgesic consumption and the improvement in performance status observed in 12 patients [six patients with partial response (PR) and six patients with stable disease (SD)] (22.6%), while the rates of the clinical benefit response in patients with PR and with SD were 100% and 50% respectively. Cisplatin plus infusional 5-FU combination seems to improve disease-related symptoms (clinical benefit response) of patients with advanced gastric cancer, even in patients without objective response.

Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group.

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m(-2) intravenously (i.v.) on day 1, respectively, and it was 175 mg m(-2) on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines.

A randomized trial of four cycles of adjuvant AC (adriamycin + cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node positive patients with breast cancer.

BACKGROUND: Four cycles of AC have been accepted as the standard chemotherapy in breast cancer. In the present randomized study we aimed to assess the efficacy of adjuvant etoposide + cisplatin (EP) combination following four cycles of standard adriamycin + cyclophosphamide (AC) in premenopausal patients with operable breast cancer and axillary lymph node metastasis. PATIENTS AND METHODS: Premenopausal patients with positive axillary lymph nodes following curative modified radical mastectomy were randomized to either four cycles of AC (82 patients) or four cycles of AC + two cycles of EP (83 patients). RESULTS: Median follow-up is 72 months. All randomized and eligible patients are included in the analysis (AC: 80 patients, AC + EP: 78 patients). The five-year disease-free survival (DFS) for the AC + EP group was significantly better when compared to AC group (45.5% vs. 30.4%; P = 0.048). Again, the five-year overall survival (OS) of the whole group was in favor of AC + EP arm, though without statistical significance (68.6% vs. 59.1%; P = 0.247). CONCLUSION: Two cycles of EP following four cycles of AC decreased the relapse rate in operable breast cancer patients.

Prospective randomized comparison of morning versus night daily single subcutaneous administration of granulocyte-macrophage-colony stimulating factor in patients with soft tissue or bone sarcoma.

BACKGROUND: Hematopoietic growth factors (HGFs) have been used to reduce the neutropenic complications of cytotoxic chemotherapy so that higher doses may be given. The authors have previously shown that endogenous serum granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) levels at night (p.m.) were significantly higher than those in the morning (a.m.). METHODS: Twenty-four patients with soft tissue or bone sarcoma who were treated with high dose ifosfamide-based chemotherapy were enrolled in this study. Patients were randomized to either a.m. or p.m. treatment. GM-CSF was administered at a dose of 5 microg/kg/day at 10 a.m. or 10 p.m., beginning 36-48 hours after the last chemotherapy dose. GM-CSF therapy was continued until the neutrophil count exceeded 1,000/mm3 for 2 consecutive days. Leukocyte, neutrophil, monocyte, and platelet counts were measured immediately before GM-CSF administration and exactly 12 hours after the first dose of GM-CSF, and every 24 hours until 3 days after the cessation of GM-CSF. RESULTS: The mean duration of Grade 3-4 neutropenia was 5.3 +/- 0.4 days for the a.m. treatment arm and 6.5 +/- 0.3 days for the p.m. treatment arm (P = 0.017). Although the duration of neutropenia in the a.m. arm was significantly shorter than in the p.m. arm, there were no differences related to the number of febrile neutropenic episodes or the duration of antibiotic administration. Also, there were no differences in the side effects observed in the a.m. and p.m. arms. CONCLUSIONS: The finding of 1.2 days' difference in the duration of Grade 3-4 neutropenia warrants further study of chronotherapy with HGFs.

Clinicopathologic features and prognostic factors of primary extranodal non-Hodgkin's lymphomas in Turkey.

Clinical, histopathologic, and prognostic features of 114 patients with primary extranodal non-Hodgkin's lymphoma were evaluated. Median age of the patients was 48 (range, 15-76) and the ratio of male/female was 55/59. Thirty-seven patients had stage 1, 55 patients stage II, 6 patients stage III, and 16 patients stage IV. The most common sites of primary extranodal non-Hodgkin's lymphoma were the gastrointestinal (GI) tract and head-neck region. Stomach (66%) and tonsils (33%) were the most frequently involved organ in GI tract and head-neck region, respectively. Eighty percent of patients had intermediate or high-grade lymphomas, 20% had low-grade subtypes. Complete remission was achieved in 83% of all patients with chemotherapy +/- radiotherapy +/- surgery. Overall and disease-free survival at 5 years were 63% and 59%, respectively. In conclusion, clinical and histopathologic characteristics and prognosis of our cases with primary extranodal non-Hodgkin's lymphoma were usually similar to those of the cases in Western countries with some differences in the incidence of some specific primary extranodal non-Hodgkin's lymphomas and in the histopathologic subtypes.

Sialic acid in childhood renal diseases: correlation with clinical and laboratory indices.

There are many kinds of glycoproteins that have sialic acid residues and it has been reported that these are elevated in some renal diseases and their significance in the pathogenesis of several renal diseases has been investigated. In the present study the serum and urine levels of sialic acid were measured in healthy controls and in children with either poststreptococcal acute glomerulonephritis (PSAGN) or minimal change nephrotic syndrome (MCNS) to test if there is any correlation with clinical and laboratory indices. In PSAGN and MCNS patients the serum and urine sialic acid concentrations at onset and relapse were significantly different from healthy controls (Mann-Whitney U-test P < 0.005). There was not a significant correlation between the clinical severity, serum creatinine and complement C3 levels and serum sialic acid concentrations in PSAGN patients. Also there was not a significant correlation between edema, serum albumin, IgG, transferrin, alpha-1-antitrypsin and serum sialic acid concentrations in MCNS patients. Although high serum and urine sialic acid levels were found in both PSAGN and MCNS patients, it does not have any clinical significance nor is it important as a diagnostic or prognostic marker.