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 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.

The clinicopathological significance of Bax and Bcl-2 protein expression with tumor infiltrating lymphocytes in ovarian carcinoma.

The aim of the study was to establish the prognostic and predictive value of Bax and Bcl-2 proteins in conjunction with the host immune response in primary epithelial ovarian carcinoma.83 patients were evaluated. Immunohistochemical staining was performed using anti-Bcl-2 (Dako; clone 124) and anti-Bax (Springbio; E17994) monoclonal antibodies. Additionally, the number of lymphocytes within tumor stroma lymphocyte nests were counted. Bcl-2 protein expression was lower in advanced stage than early stage (p= 0.005). High (H) Bax expression was associated with longer overall survival (OS) than lower (L) Bax expression (p=0.03). The OS of the (L) Bax/(L) Bcl-2 group was shorter than (H) Bax/(L) Bcl-2 group in advanced stage (p=0.05). The platinum-sensitive group had a statistically significant tendency for high Bax expression (p=0.04). Furthermore, the intensity of the lymphocyte infiltration was associated with tumor differentiation (p= 0.003). Our data suggests that (H) Bax protein expression prolongs survival, predicts platinum sensitivity and can be used after confirmation of this hypothesis in further prospective studies. The combined evaluation of Bax and Bcl-2 protein expression may provide additional significant prognostic information. The quantity of lymphocyte infiltration could be important for prognostic outcome.

Micro-metastases into the uterine leiomyoma from invasive ductal breast cancer under adjuvant tamoxifen therapy: case report.

Metastasis of breast cancer to the uterus is extremely rare. However, breast cancer is the leading tumor metastasizing from extragenital organs to the uterus. The most common signs of uterine metastasis are bleeding and mass effect. Tamoxifen use is known to increase risk of endometrial cancer. Immunohistochemical staining with GCDFP can be useful in differentiating primary uterine tumors from breast cancer metastasis. Metastasis to the uterus has been reported to worsen the prognosis. Although hysterectomy has been effective on survival, treatment modality to be used in the presence of other systemic metastases is not clear. Locoregional treatments can be used in oligometastatic cases. In addition, removal of solitary organ metastasis together with bone metastasis provides improvement in survival.

The toxicity and efficacy of Nordic-FLOX regimen as adjuvant treatment of stage III colon cancer.

PURPOSE: To evaluate the toxicity and efficacy of oxaliplatin combined with the Nordic regimen of bolus 5-fluorouracil (5-FU) and leucovorin (LV) (Nordic-FLOX) as adjuvant treatment in stage III colon cancer patients. METHODS: Fifty-three patients with resected stage III colon cancer were treated with adjuvant bolus Nordic-FLOX regimen (oxaliplatin 85 mg/m(2) on day 1, bolus 5-FU 500 mg/ m(2) and bolus LV 60 mg/m(2) days 1 and 2) every 2 weeks for 12 cycles. RESULTS: The probability of disease-free survival (DFS) at a median follow-up time of 29 months was 72%. Relapse was seen in 13 (24.5%) patients. The probability of 3-year overall survival (OS) at 36 months was 85%. Grade IV neutropenia was noticed in 15.1% of the patients, grade III-IV neurotoxicity was not encountered, while grade II neurotoxicity was 17%. Gastrointestinal toxicity (mild diarrhea) was seen in 11.3% of the patients. CONCLUSION: Adjuvant treatment of stage III colon cancer with the Nordic-FLOX regimen can be an alternative regimen to infusional and other bolus regimens due to its easy administration, lower toxicity, and similar efficacy.

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.

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.

A case with three different synchronous primaries of the female genital system and their treatment.

Multiple carcinomas of the genital system are rare in the literature. We report a 43-year-old female patient who presented with 3 different synchronous primary genital system malignancies (cervix, endometrium and ovary). After Wertheim's hysterectomy there was a 4 x 2 cm residual mass for which systemic chemotherapy and radiotherapy were administered. The patient rapidly deteriorated and died due to disease progression. Registration of cases with multiple tumors in a single centre using a standardized investigation for predisposing parameters may contribute much to the management of such conditions.

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.

Combined administration of ethodolac, ascorbic acid and radiotherapy as adjuvant therapies in an extrathoracic desmoid tumor with gross postoperative residual disease; case report and review of the literature.

A 37-year-old man was admitted with an extrathoracic desmoid tumor invading the brachial plexus. Magnetic resonance imaging (MRI) of the thorax demonstrated a 20 x 9 x 14 cm mass in the supraclavicular fossa, axillary fossa and the right side of the chest. It invaded the brachial plexus and circumscribed the subclavian and axillary arteries concentrically. Biopsy revealed desmoid tumor which was resected subtotally with the brachial plexus. The gross residual mass was treated postoperatively with radiotherapy (60 Gy) which resulted in major regression of the mass. Following radiotherapy, ethodolac with ascorbic acid were administered. The tumor was clinically indiscernible 35 months post-radiotherapy. This case shows the high effectiveness of radiotherapy along with less toxic medical treatment modalities in instances where local control is hard to achieve with surgery and highlights the importance of using multidisciplinary treatments to maintain good functional results.

Infratemporal fossa and maxillary sinus metastases from colorectal cancer: a case report.

Head and neck metastases from colorectal carcinoma are very rare. We report on a 47-year-old woman who had a vegetating tumor located at the distal sigmoid colon with initial liver metastases. She underwent palliative transverse colostomy to prevent intestinal obstruction. She was then treated with 5-fluorouracil, leucovorin and CPT-11. At the third cycle she presented with toothache and numbness of her upper lip. Computed tomography (CT) of the head and neck showed a gross mass involving the sphenoid sinus, left maxillary sinus, left pterygopalatine plate, pterygopalatine and infratemporal fossa. Histology of the mass revealed metastatic adenocarcinoma which was similar with the primary sigmoid carcinoma. The patient underwent radiotherapy and died 2 months later. Although cranial fossa metastases from colorectal cancer are very rare, the physicians should be aware of this type of metastatic pattern in patients who suffer of toothache, painful mastication or numbness of the lips, especially if decay has not been determined.