Melek Erkisi

Risk factors for developing cardiotoxicity of trastuzumab in breast cancer patients: An observational single-centre study

Background Trastuzumab is a recombinant humanized monoclonal antibody used to treat human epidermal growth factor receptor 2 positive breast cancer, with recognized associated cardiotoxicity. In this retrospective observational study, we investigated associated cardiotoxicity on clinical outcomes using trastuzumab in women referred to our clinic. Materials and methods The study was made up of 111 women with human epidermal growth factor receptor 2-overexpressing breast cancer who received trastuzumab in the Medical Oncology Department, between 2010 and 2013. Results A > 10% reduction of the baseline fraction of the left ventricular ejection fraction was observed in 18 (16.21%) women. Two individuals (1.8%) suffered from symptomatic heart failure, seven women showed cardiac symptoms and nine women showed asymptomatic decline of left ventricular ejection fraction. Risk factors for cardiotoxicity in the group included: postmenopausal status (p = 0.01), hypertension (p = 0.002), obesity (p = 0.0001), previously diagnosed coronary artery disease (p = 0.0001) and smoking (p = 0.03). Conclusion The aforementioned factors pose a risk for cardiotoxicity. We found postmenopausal status, hypertension, obesity, previous coronary artery disease and smoking to be associated with an increased risk of cardiac dysfunction in women using trastuzumab. While administering trastuzumab to women who have these conditions, one must be aware of the risk of cardiotoxicity of trastuzumab.

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with Stage III-B and IV non-small cell lung cancer

Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 x day x 5, ifosfamide: 1.8 g/m2 x day x 5, mesna: 1.2 g/m2 x day x 5, etoposide: 100 mg/m2 x day x 5 (ICE) or cisplatin: 20 g/m2 x day x 5 and etoposide: 100 mg/m2 x day x 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable.

Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

BACKGROUND Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. METHODS This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+, HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. RESULTS Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenopausal and 31 (49.2%) were postmenopausal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. CONCLUSION pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.

Primary therapeutic decision-making in inoperable non–small cell lung cancer

PURPOSE To test the accuracy of our treatment decisions for patients with inoperable non-small cell lung cancer (NSCLC) using a prototype decision-support system (DSS) and a prognostic index (PI). METHODS AND MATERIALS To predict patient outcome and select optimal treatment, the systems protocol was tested retrospectively in 242 patients with Stage I-IV disease. The PI was determined in 184 patients with Stage I-IIIa,b disease. Survival was the final determinant of the accuracy of our treatment decisions. RESULTS Until 1996 it was our treatment policy to treat all Stage III patients with radical intent unless they had symptoms requiring palliation. In 1997, after the palliation concept of the DSS and the PI were changed to include all Stage III disease, there was considerable discordance between the rates of palliative treatment indicated by the DSS and the PI (69% and 99%, respectively) as well as that observed in our practice (30% in the DSS group and 20% in the PI group, respectively). There was also a significant difference in survival between the patients in the low- and high-risk categories defined by the PI (median survival of 12 versus 6 months, respectively; p = 0.0001). In the group that received radical radiotherapy, there was also a significant difference in the duration of survival between the low- and high-risk groups (median survival of 12 versus 8 months, respectively; p = 0.01). In addition, the risk categories proved to be the most important predictor of survival in the patients receiving radiotherapy longer than 2 weeks (median survival of 12 versus 7 months, respectively; p = 0.0001). In high-risk patients, however, the duration of radiotherapy did not have a significant impact on survival (p = 0.25). CONCLUSION Our data indicate that the PI is a useful method for selecting radical or palliative treatment modalities as well as for determining treatment duration.

Evaluation of endometrial thickness and bone mineral density based on CYP2D6 polymorphisms in Turkish breast cancer patients receiving tamoxifen treatment.

Background: Several previous studies have examined the effect of CYP2D6 gene polymorphism on the efficacy and metabolism of tamoxifen (Tamoxifen Teva, Nolvadex) in the treatment of breast cancer. In the present study, the metabolic profiles associated with various CYP2D6 genotypes were evaluated. Method: In the present study 92 Turkish breast cancer patients with early-stage hormone receptor-positive tumors treated with adjuvant tamoxifen (20 mg) were evaluated for CYP2D6 genotype and metabolic profiles. Known side effects of tamoxifen treatment, including endometrial thickening, changes in serum lipid levels and bone density, and hepatosteatosis, were evaluated according to the CYP2D6 polymorphism. Result: The distribution of metabolic characteristics in the Turkish population was as follows: 77.1% normal metabolism, 11.5% intermediate metabolism, 5.2% ultrarapid metabolism, and 2.1% poor metabolism. The CYP2D6 genotypes associated with rapid metabolism were CYP2D6 3X*1/*1 duplication (DUP) and CYP2D6 2X*1/*2, while poor metabolism was associated with the genotypes CYP2D6 *3/*4 and CYP2D6 *6/*6. There was no statistically significant relationship between metabolic characteristics and bone density or hepatosteatosis. A statistically significant difference in total cholesterol and triglycerides was detected in lipid profile analysis (p = 0.003, p = 0.02). Assessment of endometrial thickness revealed a significant association of hyperplasia and poor metabolism, and an association between atrophy and ultrarapid metabolism (p = 0.01). Conclusion: Significant development of endometrial hyperplasia was identified among individuals with poor tamoxifen metabolism. As a result, tamoxifen may be a significant predictor of endometrial thickening among individuals with poor metabolic characteristics.

Retrospective Analysis of 119 Osteosarcomas in a Single Centre Experience

Aim: Osteosarcomas must be managed by a team which includes pathologists, radiologists, surgeons, radiation therapists, and medical oncologists. Treatment modalities and demographic charasteristics of osteosarcomas were analysed in this study. Material and Method: Primary osteosarcomas treated between 1999-2010 in Cukurova University Medical Faculty Department of Medical Oncology were analysed retrospectively. Results: Of the total 119 patients, 74% were male and 26% female. The median age was 19. The median follow up time was 37 months. The most frequently seen sarcomas were osteoblastic at 82.4%. Localization of the disease was found to be 55% in the lower extremity, 14.1% in the upper extremity, 13% in the head-neck, 6.6% in the thoracic area, and 4.1 % in the pelvic region. Some 6.41% were local stage, 25.64% locally advanced, 15.8% metastatic, and 14.10% were diagnosed with nuks disease. Chemotherapy was administered in 77 of 119 patients. Patients received different treatments: 23.1% were treated with preoperative chemotherapy, 16.67% postoperative, 9.52% palliative, 33.33% preoperative+postoperative, 2.38% postoperative+palliative, 9.52% preoperative+postoperative+palliative chemotherapy, and 4.76% of the patients did not receive chemotherapy. Both radical and conservative surgery was performed. The most common metastatic site was the lungs. The overall length of survival was 65 months (95%CI 30-59). The survival rates did not vary between the groups of preoperative, postoperative, preoperative+postoperative chemotherapy and other groups (respectively 23 versus 36 versus 28 versus 44 months) (p=0.8). No differences were evident for radiotherapy (p=0.06). Discussion: Osteosarcomas can be treated successfully with surgery, chemotherapy, and radiotherapy. There was no cumulative survival difference in results based on the types of chemotherapy used in this study. These results show the importance of a multimodality treatment approach including surgery, chemotherapy, and radiotherapy.

1654PTHE EVALUATION OF FIBROBLAST GROWTH FACTOR RECEPTOR 1 (FGFR1), FIBROBLAST GROWTH FACTOR 2 (FGF2), PHOSPHATIDYLINOSITOL 3 PHOSPHATE KINASE (IP3K) EXPRESSION AND THEIR CLINICAL, PROGNOSTIC SIGNIFICANCE IN EARLY AND ADVANCED STAGE OF SQUAMOUS CELL CARCINOMA OF THE LUNG

ABSTRACT Aim: Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer-related death in the world. squamous cell carcinoma (SCC) of the lung is the second most frequent histologic subtype of lung carcinoma. Recently, growth factors, growth factor receptors and signal transduction system related gene amplifications and mutations have been under extensive investigation to estimate the prognosis or to develope indivilualized therapies in SCC. In this study, besides signal transduction molecule (IP3K p110a), we explored the expressions of growth factors/receptors (FGFR1, FGF2) in tumor tissue and also their clinical or prognostic significance in patients with early/advanced diseases of SCC. Methods: From 2005 to 2013, 129 patients (23 early disease, 106 advanced disease) with a histopathological SCC diagnosis were selected from hospital files of Cukurova University Medical Faculty for this study. In 99 patients with sufficient tissue samples, FGFR1, FGF2 and PI3K (p110a) expressions in both tumor and stromal tissue were evaluated with immunohistochemistry by two independent pathologists. Considering survival analysis seperately for patients with both early and advanced stage diseases, the relationship between the clinical features of patients and expressions were evaluated by univariate and multivariate analysis. Results: FGFR1 expression was found to be low in 59 (60%) patients and high in 40 (40%) patients. For FGF2; 12 (12%) patients had high, 87 (88%) patients had low expression, and for IP3K, 31 (32%) patients had high and 66 (68%) patients had low expressions In univariate analysis, survival was significantly associated with stage and performance status (PS) (p Conclusions: Thereis no effective individualized treatment for SCC yet. Therefore, for developing such a treatment in future, it is essential to identify the genetic abnormalities that are responsible for the biological behaviours and carcinogenesis of SCC. Although we could not show the prognostic and predictive significance of FGFR1, FGF2 and IP3K expressions in SCC, we determined the expression rates of FGFR1, FGF2 and IP3K as a reference for Turkish patients. However, we layed emphasis on the fact that pulmonary fibrosis, which is a late complication of radiotherapy at stage III disease, and the scar of tuberculosis could be associated with FGFR1 and FGF2 expressions. Disclosure: All authors have declared no conflicts of interest.

Adjuvant use of antiprolactin, antiestrogen, and cytotoxic chemotherapy for breast cancer

Abstract Between September 1, 1985 and September 1, 1989, 110 premenopausal patients with estrogen-receptor-positive, stage-II breast cancer were randomized to receive, as adjuvant treatment following radiotherapy, either cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) + tamoxifen (T) + bromocriptine (B) bases or CMF + T only. Preoperative serum prolactin (PRL) levels or PRL-receptor status of the tumor were not available, but before the commencement of adjuvant therapy serum PRL levels were measured in all patients and found to be high in 28. The local (LR) and distant (DM) metastasis-recurrence rates were lower in patients given bromocriptine (CMF + T + B) (LR, 5.7%; DM, 10.9%) than in those not given bromocriptine (CMF + T) (LR, 10.9%; DM, 27.2%); these findings, however, were not significant ( P > 0.05). In the 28 hyperprolactinemic patients the metastasis-recurrence rate (17/28) was higher ( P = 0.0001) and disease-free survival was shorter ( P = 0.001) than in the 80 normoprolactinemic patients. It was also demonstrated that the disease-free survival was longer ( P = 0.009) and the metastasis-recurrence rate was lower (6/12) in hyperprolactinemic patients who received bromocriptine (CMF + T + B) than in hyperprolactinemic patients who did not (CMF + T) (11/16), while there was no difference in metastasis-recurrence rates and disease-free survival between the two treatment groups among normoprolactinemic patients. These results encourage further investigation of the action of bromocriptine adjuvant base. Baseline serum PRL measurement and tumor PRL-receptor determination could be valuable tools to identify the appropriate cases for antiprolactinemic treatment.

Empiric therapy in the management of febrile neutropenic cancer patients

Abstract The effectiveness of empiric therapy was evaluated in 186 cancer patients who experienced 417 febrile and neutropenic episodes during the last 4 years. Ninety-eight patients experiencing 244 episodes were treated with empiric antibiotic therapy with mezlocillin and tobramycin. The response rate to the empiric treatment was 88% for bacterial infections and 58% for unexplained fever. Fluconazole 200 mg IV daily was added to the empiric antibiotic therapy in the subsequent 173 episodes experienced by 90 patients, of whom 12 had also been evaluated in the previous group. The addition of fluconazole improved the response rates to 90% in bacterial infections and to 86% in unexplained fever. In proven fungal infections in neutropenic patients, empiric antibiotic therapy combined with higher doses of fluconazole seemed beneficial. This study suggests that fluconazole 200 mg IV daily is an effective adjunct to empiric antibiotic therapy, but higher doses of fluconazole are preferable in proven fungal infections.