Mustafa Dikilitas

Protective effects of nebivolol against anthracycline-induced cardiomyopathy: A randomized control study

BACKGROUND We aimed to evaluate the effect of prophylactic nebivolol use on prevention of antracycline-induced cardiotoxicity in breast cancer patients. METHODS In this small, prospective, double-blind study, we randomly assigned 45 consecutive patients with breast cancer and planned chemotheraphy to receive nebivolol 5mg daily (n=27) or placebo (n=18). Echocardiographic measurements and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels were obtained at baseline and at 6-month of chemotherapy. RESULTS Both studied groups had comparable echocardiographic variables and NT-pro-BNP levels at baseline. At 6-month, the left ventricular (LV) end-systolic and end-diastolic diameters increased in the placebo group (LVESD: 29.7 ± 3.4 to 33.4 ± 4.5mm; LVEDD: 47.2 ± 3.8 to 52.0 ± 4.6mm, p=0.01 for both) but remained unchanged in the nebivolol group (LVESD: 30.4 ± 3.5 to 31.0 ± 3.6mm, p=0.20; LVEDD: 47.0 ± 4.4 to 47.1 ± 4.0mm, p=0.93). The placebo group also had lower LVEF than the nebivolol group (57.5 ± 5.6% vs. 63.8 ± 3.9%, p=0.01) at 6-month. NT-pro-BNP level remained static in the nebivolol group (147 ± 57 to 152 ± 69 pmol/l, p=0.77) while it increased in the placebo group (144 ± 66 to 204 ± 73 pmol/l, p=0.01). CONCLUSIONS Prophylactic use of nebivolol treatment may protect the myocardium against antracycline-induced cardiotoxicity in breast cancer patients.

Association between the Thr431Asn polymorphism of the ROCK2 gene and risk of developing metastases of breast cancer.

The objective of this study was to analyze the genotype distributions and allele frequencies for ROCK2 Thr431Asn and Arg83Lys polymorphisms among breast cancer patients. In this case-control study, 223 patients with breast cancer were recruited and divided into two groups according to metastases (n = 128) and without metastases (n = 95). Genomic DNA from the patients and the control cases (n = 150) was analyzed by real-time PCR using a Light-Cycler. Neither genotype distributions nor the allele frequencies for the Arg83Lys polymorphism showed a significant difference between the groups. Although no marked changes were observed with nonmetastatic group, a statistically significant association was found between the control and metastatic group for the Thr431Asn polymorphism. Although homozygous carriers of the Thr431Thr genotype were more frequent, heterozygous carriers of the Thr431Asn genotype were less frequent among the metastatic patients than among controls. There was also an increase in Thr431 allele (60.5% in patients vs. 51.7% in controls) and decrease in Asn431 allele frequencies (48.3% in control vs. 39.5% in metastatic patients) in metastatic groups (p = 0.036). Our results demonstrate that Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis.

Effects of Cyanocobalamin on Immunity in Patients with Pernicious Anemia

Objective: The aim of the study was to evaluate the role of vitamin B12 in patients with pernicious anemia. Materials and Methods: This study was conducted prospectively at the Turgut Özal Medical Center, Department of Hematology, between April and November 2002. Absolute numbers and ratio of the surface antigens of T and B lymphocyte subgroups, CD4/CD8 ratio were calculated in order to evaluate changes in leukocyte and lymphocyte numbers; natural killer (NK) cell count, serum C3, C4, and levels of immunoglobulins G, A, and M were also measured to evaluate vitamin B12 effect on immunity. Values obtained before treatment with cyanocobalamin were compared with those found during peak reticulocyte count. Results: In vitamin B12-deficient patients, absolute numbers of CD4+ and especially CD8+ lymphocytes were found to be decreased; CD4/CD8 ratio increased, and NK cell activity was depressed. After cyanocobalamin treatment, absolute numbers and percentage of lymphocyte subgroups were elevated. Increased CD4/CD8 ratio and depressed NK cell activity were restored and levels of C3, C4, and immunoglobulins were elevated. Conclusion: These findings suggest that vitamin B12 has important immunomodulatory effects on cellular immunity, and abnormalities in the immune system in pernicious anemia are restored by vitamin B12 replacement therapy.

Positive effects of oral β-glucan on mucositis and leukopenia in colorectal cancer patients receiving adjuvant FOLFOX-4 combination chemotherapy.

The present study aimed to determine the effect of oral β-glucan on mucositis and leukopenia in 62 consecutive patients with colorectal cancer treated with an adjuvant FOLFOX-4 regimen. The patients were retrospectively evaluated in 2 groups: one group received β-glucan and the other did not (control group). Leucocytes, neutrophils, and platelets were evaluated before and 1 week after chemotherapy and oral mucositis and diarrhea were noted. Leucocyte and neutrophil counts after chemotherapy in the β-glucan group were 7,300/mm3 and 3,800/mm3, respectively, and the reductions, as compared to baseline, were not significant (p=0.673 and 0.784). The median platelet count was 264,000/mm3 after chemotherapy in the β-glucan group and the reduction, as compared to baseline, was borderline significant (p=0.048). In the control group, reduction in leucocyte, neutrophil, and platelet counts was statistically significant. Oral mucositis and diarrhea were less common in the β-glucan group. We conclude that β-glucan can be used to reduce the adverse effects of chemotherapy.

Do thrombophilic gene mutations have a role on thromboembolic events in cancer patients

Aim:  Thromboembolism is common in patients with cancer and may be considered a major cause of morbidity and mortality. We studied the most common genetic polymorphism characteristics that may have roles in the development of thrombosis in patients with cancer.

Modified Docetaxel and Cisplatin in Combination with Capecitabine (DCX) as a First-Line Treatment in HER2-Negative Advanced Gastric Cancer

BACKGROUND Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. MATERIALS AND METHODS Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. RESULTS The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. CONCLUSIONS DCX regimen offers prominent anti-tumor activity and considered to be effective first- line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Recovery of paraneoplastic hypercalcemia by sunitinib treatment for renal cell carcinoma: a case report and review of the literature

Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor. İt has higher response rates and progression-free survival in patients with metastatic renal cell carcinoma (RCC) when compared with standard chemotherapy and interferon-α. We report a case of paraneoplastic hypercalcemia, resistant to conventional treatment but recovers by sunitinib treatment as the first case in the literature, in a 33-years-old man with metastatic RCC. At the sixth month of follow-up period, in this case, serum calcium level was still in normal ranges. Besides sunitinib is effective in symptom control, it is also helpful in management of paraneoplastic hypercalcemia, a life-threatening entity.

Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer

OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m2 docetaxel and 20 mg/m2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC.

The effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy.

The aim of this study was to examine the effect of being overweight on survival in patients with gastric cancer undergoing adjuvant chemoradiotherapy and chemotherapy. In this study 152 patients were evaluated. Radiotherapy dose was 45 Gy given in 5 weeks. 5-FU 425 mg/m(2) and folinic acid 20 mg/m(2) were administered weekly during the radiotherapy and four cycles with 4-week intervals as consolidation chemotherapy after radiotherapy. Patients were assigned into two groups according to their body mass index: overweight (body mass index ≥25 kg/m(2)) and normal weight (body mass index <25.0 kg/m(2)). The median overall survival was 39 months vs. 18 months and median disease-free survival was 27 months vs. 13 months in the overweight and normal-weight groups respectively (P = 0.004 and P = 0.006 respectively). The 5-year survival was better in the patients with overweight than those with normal weight (42% vs. 17%; P = 0.004). The overall survival was significantly better with being overweight and early pathological stage (P = 0.016 and P = 0001 respectively). Overall survival, disease-free survival and long-term survival in patients with gastric cancer undergoing adjuvant treatment were better in overweight than normal-weight patients. Moreover, it was shown that body mass index and pathological stage were associated to survival and prognosis.

The effect of small-molecular-weight heparin added to chemotherapy on survival in small-cell lung cancer - A retrospective analysis

Aims and Background: Small cell lung cancer (SCLC) is a chemotherapy-responsive tumor and associated with alterations in the coagulation system. Addition of low-molecular-weight heparin (LMWH) to combination chemotherapy (CT) had resulted in increase in survival. The present retrospective trial was designed to determine whether the duration of dalteparin usage has an effect on progression and survival. Materials and Methods: The medical records of 67 patients with SCLC who were given cisplatin-etoposide and concomitant LMWH (dalteparin) was evaluated retrospectively. Results: Median follow-up of patients was 11.3 months. Outcome: 10.6% complete response, 3.0% good partial response, 36.4% partial response, 10.6% stable disease, and 39.4% progressive disease. Side-effects were seen in 40.3% of the patients. Median dalteparin duration was 6,1 months. According the duration of dalteparin patients were grouped in three: who took dalteparin less than 4 months (Group A), 4-6 months (Group B) and more than 6 months (Group C). Mean overall survival (OS) in Group A was 6.5 months, in Group B 11.8 months, and Group C 14.6 months. Mean OS in Group B and C were statistically significantly (P < 0.001) longer than Group A, between Group B and C there was not any significant difference (P = 0.037). Mean progression free survival (PFS) was 9 months. Conclusions: The CT plus LMWH minimum 4 months long is well-tolerable, and may improve PFS and OS in patients with SCLC. For treatment of patients with SCLC CT plus LMWH may be considered as effective future-therapy, and further multi-centre randomised prospective clinical trials must be done to determine the new standard treatment approach for SCLC.