First-line nivolumab plus ipilimumab versus chemotherapy in patients with unresectable malignant pleural mesothelioma: 3-year outcomes from CheckMate 743.

BACKGROUND: In the phase III CheckMate 743 study (NCT02899299), first-line nivolumab plus ipilimumab significantly improved overall survival (OS) versus chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). We report updated data with 3-year minimum follow-up. PATIENTS AND METHODS: Adults with previously untreated, histologically confirmed, unresectable MPM and Eastern Cooperative Oncology Group performance status of ≤1 were randomized 1 : 1 to nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks) for up to 2 years, or six cycles of platinum plus pemetrexed chemotherapy. This report includes updated efficacy and safety outcomes, exploratory biomarker analyses including four-gene inflammatory expression signature score, and a post hoc efficacy analysis in patients who discontinued treatment due to treatment-related adverse events (TRAEs). RESULTS: With a median follow-up of 43.1 months, nivolumab plus ipilimumab continued to prolong OS versus chemotherapy. Median OS was 18.1 versus 14.1 months [hazard ratio (95% confidence interval), 0.73 (0.61-0.87)], and 3-year OS rates were 23% versus 15%, respectively. Three-year progression-free survival rates were 14% versus 1%, and objective response rates were 40% versus 44%. At 3 years, 28% versus 0% of responders had an ongoing response. Improved survival benefit with nivolumab plus ipilimumab versus chemotherapy was observed across subgroups, including histology. A high score of the four-gene inflammatory signature appeared to correlate with improved survival benefit with nivolumab plus ipilimumab. No new safety signals were observed with nivolumab plus ipilimumab, despite patients being off therapy for 1 year. In patients who discontinued nivolumab plus ipilimumab due to TRAEs, median OS was 25.4 months, and 34% of responders maintained their responses for ≥3 years after discontinuation. CONCLUSIONS: With 3 years' minimum follow-up, nivolumab plus ipilimumab continued to provide long-term survival benefit over chemotherapy and a manageable safety profile, supporting the regimen as standard-of-care treatment for unresectable MPM, regardless of histology.

Photodynamic Therapy of Melanoma B16 with Chlorin E6 Conjugated with a PSMA-Ligand.

The efficacy of a new photosensitizer of chlorin E6 conjugated with a prostate-specific membrane antigen (PSMA) in photodynamic therapy of murine melanoma B16 was studied in in vivo experiments. The dynamics of photosensitizer accumulation in the tumor and surrounding tissues was evaluated and antitumor efficacy of photodynamic therapy was assessed by parameters of regression and morphological characteristics of experimental transplanted melanoma B16. The inhibitory effect of photodynamic therapy on melanoma was evaluated by complete regression of the tumor, absolute tumor growth coefficient in animals with continuation of tumor growth, and the increase in life span in comparison with the control; the criterion of cure was the absence of signs of tumor recurrence in mice within 90 days after therapy. The therapeutic potential of photodynamic therapy was determined by devitalization of tumor cells (histological examination of the zones of laser exposure on day 21 after treatment). The photosensitizer with PSMA-ligand exhibited high antitumor activity in photodynamic therapy for melanoma B16. Photodynamic therapy carried out at the optimum time after photosensitizer injection with experimentally determined parameters of laser exposure allows achieving the maximum inhibitory effect on melanoma. Pathomorphological study in the zones of exposure detected no survived tumor cells.

Photodynamic Therapy of Sarcoma M-1 in Rats with Photosensitizer Photoran E6.

We studied the effectiveness of photodynamic therapy with the photosensitizer Photoran E6 on the model of rat sarcoma M-1 positive for mutant p53 gene. Experiments showed that Photoran E6 exhibits high antitumor activity in photodynamic therapy of solid tumor of the connective tissue. Photodynamic therapy carried out during the optimal period after injections of Photoran E6 with the determined parameters of laser exposure allows achieving the maximum inhibitory effect on sarcoma M-1: 100% cured animals. Immunohistochemical study revealed no live tumor cells with expression of the mutant p53 protein in areas of photodynamic exposure.

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.

Modifying Effect of Autotransfusion of Mesenchymal Stromal Cells on the Production of Reactive Oxygen Species and Cytokines by Mononuclear Cells in Patients with Chronic Heart Failure.

We studied in vivo modifying effect of autotransfusion of human bone marrow mesenchymal stromal cells on ROS generation and production of cytokines (TNFα,TNFß, IL-1α, IL-10, IFNγ, and GM-CSF) and PGE2 by mononuclear cells of patients (N=21) with chronic heart failure. These parameters were evaluated prior to (control) and after (immediately and on day 14) intravenous administration of stromal cells in doses of 100-200×106. Immediately after autotransfusion, significant increase of in vitro zymosan-induced chemiluminescence of blood mononuclear cells from 10 patients was observed. At later terms after autotransfusion (day 14), inhibition of chemiluminescent activity of blood mononuclear cells was revealed in 50% patients. We discuss possible mechanisms of involvement of transplanted autologous bone marrow mesenchymal stromal cells in reprogramming of blood mononuclear phagocytes from the pro- to anti-inflammatory phenotype under conditions of their in vivo interaction manifesting in transition from activation to inhibition of ROS-producing activity of macrophages and significant suppression of in vitro LPS-induced production of TNFα and GM-CSF by blood mononuclears against the background of significantly elevated TNFß, IL-10, and IL-1α concentrations.

Efficacy of photodynamic therapy for basal cell carcinoma using photosensitizers of different classes.

The paper presented results of photodynamic therapy for 139 patients with basal cell carcinoma. We conducted a study of the efficacy and safety of four methods of photodynamic therapy. There were used the following photosensitizers: photohem, photosens, photolon and photodithazine. Photodynamic therapy using photosensitizers of chlorine series (photolon and photoditazin) provides a better long-term results improving disease-free 3-year survival rate to 90.4% and 92.3%, respectively compared to 54.7% and 71.1% in groups, in which treatment was restricted by photohem and photosens.

Development of bacteriochlorophyll a-based near-infrared photosensitizers conjugated to gold nanoparticles for photodynamic therapy of cancer.

We report the synthesis and characterization of a new sulfur-containing derivative of bacteriochlorophyll a. The latter was isolated from biomass of the nonsulfur purple bacterium Rhodobacter capsulatus strain B10. The developed photosensitizer is N-aminobacteriopurpurinimide with an exocyclic amino group acylated with a lipoic acid moiety, which is a biogenic substance that acts as a cofactor of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes in the body. The disulfide moiety of lipoic acid confers the compound aurophilicity, thus allowing its conjugation with gold nanoparticles (NP-Au) via S-Au bonds. The shape and the size of the resulting nanoconjugate with immobilized photosensitizer (PS-Au) were assessed by dynamic light scattering and transmission electron microscopy. The conjugated nanoparticles are spherical with hydrodynamic diameter of 100-110 nm. The PS-Au conjugate absorbs light at 824 nm and emits strong fluorescence at 830 nm, which allowed in vivo study of its dynamic biodistribution in rats bearing sarcoma M-1. Compared to the free photosensitizer, PS loaded on the gold nanoparticles (PS-Au) showed extended circulation time in the blood and enhanced tumor uptake due to nonspecific passive targeting when the drug accumulates in tumor sites through the leaky tumor neovasculature and does not return to the circulation.

Hypoglycemic Effect of the Methanol flower Extract of Piper Claussenianum and the Major Constituent 2',6'-dihydroxy-4'-methoxychalcone in Streptozotocin Diabetic Rats.

Piper claussenianum inflorescences crude methanol extract was tested for hypoglycemic effect in streptozotocin-induced diabetic rats. The blood glucose levels of rats treated with methanol extract were reduced from 318.4±28.1 mg/dl before treatment to 174.2±38.3 mg/dl after 12 days of treatment (P<0.05). Phytochemical studies were carried out on inflorescences methanol crude extract in order to investigate the possible metabolites responsible for the pharmacological properties of the extract. After chromatographic procedures, three flavonoids were isolated and characterized. The major compound 2',6'-dihydroxy-4'-methoxychalcone was also tested. Rats that received the chalcone content also displayed a reduction in blood glucose levels from 277.4±7.7 mg/dl before treatment to 158.8±9.2 mg/dl after 12 days of treatment (P<0.05). The results suggest this chalcone is one of the metabolite responsible for the blood glucose levels reduction in rats with streptozotocin-induced diabetes. The inflorescence crude extract of P. claussenianum was found to be composed mainly by flavonoids and may be a potential natural source of compounds with hypoglycemic properties.

Screening antimycobacterial activity of Baccharis dracunculifolia, Centella asiatica, Lantana camara and Pterodon emarginatus / Atividade anti-micobacteriana de Baccharis dracunculifolia, Centella asiatica, Lantana camara e Pterodon emarginatus

ABSTRACT The permanent investigation of new antimycobacterial drugs is necessary for the eradication programs of tuberculosis and other mycobacterium-related diseases. The aim of the present study is to search for new sources of antimycobacterial drugs using plant materials. In this study, 11 plant materials (extracts, essential oils and some fractions) obtained from 4 species of medicinal plants traditionally used as general therapeutics for different illnesses and specifically as treatment of tuberculosis, were evaluated using the microplate resazurin assay against 2 species of the Mycobacterium tuberculosis Complex and 3 nontuberculous mycobacteria. The results showed the hexane extract and the essential oil from fruits of Pterodonemarginatus (Vogel) as potential sources of antimycobacterial drugs against 4 species of tested mycobacteria. The hexane fraction of methanol extract from leaves of Centella asiatica also presented significant mycobacterial growth inhibition, but against M. chelonae only. In conclusion, it was possible to contribute to the antimycobacterial investigations by presenting three new samples of plants with significant antimicrobial activity against four Mycobacteriumspp and suggest future studies about the antimycobacterial properties of fruits from P. emarginatus.

RESUMO A investigação permanente de novas drogas antimicobacterianas é necessária no programa de erradicação da tuberculose e de outras doenças relacionadas com micobactérias. O objetivo deste estudo foi buscar novas fontes de drogas antimicobacterianas usando material vegetal. Neste estudo, 11 materiais de base vegetal (extratos, óleos essenciais e algumas frações) foram avaliados contra 5 espécies de micobactérias. Estes materiais foram obtidos a partir de 4 espécies de plantas medicinais tradicionalmente utilizadas como terapêutica geral para diferentes doenças e, especificamente, no tratamento de tuberculose (Baccharis dracunculifolia, Centella asiatica, Lantana camara, Pterodon emarginatus). Os ensaios foram realizados em microplacas com resazurina contra duas espécies do Complexo Mycobacteriumtuberculosis e 3 espécies de micobactérias não tuberculosas. Os resultados mostraram o extrato hexânico e o óleo essencial de frutos de P.emarginatus como potenciais fontes para drogas antimicobacterianas contra quatro espécies de micobactérias testadas. A fração hexânica do extrato metanólico das folhas de C. asiatica também apresentou significativa inibição do crescimento de micobactérias apenas contra M.chelonae. Em conclusão, foi possível contribuir para as investigações de antimicobacterianos por apresentar três novas amostras de plantas com atividade antimicrobiana significativa contra quatro Mycobacterium spp e sugerir a realização de estudos futuros sobre as propriedades antimicobacterianas de frutos de P. emarginatus.

Photodynamic therapy of experimental sarcoma M-1 with boronated chlorine as a photosensitizer.

Using rat model of experimental sarcoma M-1 we studied the efficacy of photodynamic therapy with boronated chlorine as a photosensitizer in doses of 1.25, 2.5, 5.0, and 10.0 mg/ kg body weight. Laser irradiation was performed at energy densities of 150, 300 J/cm(2) and power density of 0.25 and 0.42 W/cm(2). Treatment efficacy was evaluated by the percentage of animals with complete tumor regression, percentage of tumor recurrence and, in cases of its growth, by tumor growth coefficient. The efficacy of photodynamic therapy depended on the dose of boronated chlorine and parameters of the laser irradiation. Optimal conditions were the dose of 2.5 mg/kg at laser energy density of 300 J/cm(2) and power density of 0.42 W/cm(2) and a dose of 5.0 mg/kg at 150 J/cm(2) and 0.25 W/cm(2).

The predictive role of Paraoxonase 1 (PON1) activity on survival in patients with metastatic and nonmetastatic gastric cancer.

BACKGROUND: Oxidative stress is known to be implicated in the pathogenesis of malignancies including gastric cancer (GC). Paraoxonase 1(PON1) is a member of antioxidant defense system which acts by hydrolysing peroxidases. Our aim is to assess the levels PON1 activity in different stages and localizations of GC and analyze the predictive role of PON1 activity on overall survival in GC. MATERIALS AND METHODS: One hundred and twenty six patients with GC were enrolled to the study. Patients were divided into two groups; group I (nonmetastatic GC, n=65) and group II (metastatic GC, n=61). Paraoxonase 1 activity, albumine and lactate dehidrogenase levels and whole blood count were analyzed. Union Internationale Contre le Cancer system was used for staging procedure. RESULTS: Patients at advanced N or M stage have significantly lower levels of PON1 (34.26 U/L and 29.88 U/L, p=0.04 and p=0.03; respectively). Gender, Lauren's classification, grade, localization and T stage of tumor have nonsignificant impact on PON1 activity. PON1 activity was a significant prognostic factor in GC as well as metastasis, localization of tumor and low hemoglobine or albumine level. CONCLUSIONS: Lower levels of paraoxonase 1 activity in patients with metastatic gastric cancer may reflect the presence of enhanced oxidative stress in advanced stages of the disease. PON1 activity is a significant and independent predictor of overall survival. Identifying novel prognostic markers can help to establish appropriate therapeutic strategies, to determine preventive measures and to improve survival rates.

A novel nerolidol-rich essential oil from Piper claussenianum modulates Candida albicans biofilm.

Candidiasis is a major opportunistic fungal infection in humans, and its incidence has increased steadily over the last two decades. Candida albicans, the main species of the genus, has a large arsenal of virulence attributes that contribute to successful infections, such as dimorphism and biofilm formation. The adverse effects of eukaryotic antimicrobial therapies associated with an increase in resistance to the compounds presently available have boosted efforts to improve the therapeutic arsenal against candidiasis with a newer and cheaper range of drugs. In this study, a novel nerolidol-rich essential oil (EO) derived from Piper claussenianum (Miq.) C. DC., Piperaceae, was tested on the growth, transition (yeast to hyphae), formation and stability of biofilms produced by C. albicans. Both inflorescence and leaf EOs were evaluated and revealed MIC values ranging from 0.04 to 0.1 % and 0.2 to 1.26 %, respectively. Furthermore, leaf EO managed to downregulate the yeast-to-hyphae transition by 81 %, as well as reducing biofilm formation by about 30 and 50 % after incubation for 24 and 48 h, respectively. The EO was also able to reduce the viability of pre-formed biofilm by 63.9 %. Finally, the association between the leaf EO and fluconazole was evaluated and revealed an interesting synergistic effect. Taken together, these results demonstrate that this novel compound could be a promising agent and could reinforce the arsenal of therapeutic alternatives for the treatment of candidiasis. Furthermore, it may represent a novel and natural source of nerolidol, which could be of interest pharmaceutically.

Is (18)F-FDG-PET/CT prognostic factor for survival in patients with small cell lung cancer? Single center experience.

BACKGROUND: Although a number of studies in patients with a variety of malignant tumors have shown that metabolic activity on fluorine-18 deoxyglucose positron emission tomography computed tomography ((18)F-FDG-PET/CT) is correlated with survival, there are few studies about the impact of (18)F-FDG-PET/CT for survival in small cell lung cancer (SCLC) patients. There is still some ambiguity as to whether FDG PET in patients with SCLC will ensure prognostic knowledge for survival. We performed a retrospective analysis of prognostic implication of (18)F-FDG-PET/CT in patients with SCLC. METHODS: We retrospectively reviewed 54 patients with histologically or cytologically proven SCLC who had undergone pre-treatment (18)F-FDG-PET/CT scanning between September 2007 and November 2011 in the Dicle University, School of Medicine, Department of Medical Oncology. SUVmax and other potential prognostic variables were chosen for analysis in this study. Univariate and multivariate analyses were conducted to identify prognostic factors associated with survival. RESULT: Among the eleven variables of univariate analysis, three variables were identified as having prognostic significance: Performance status (p < 0.001), stage (p = 0.02) and diabetes mellitus (p = 0.05). Multivariate analysis showed that performance status and stage were considered independent prognostic factors for survival (p < 0.001 and p = 0.002 respectively). CONCLUSION: In conclusion, performance status and stage were identified as important prognostic factors, while (18)F-FDG-PET/CT uptake of the primary lesions was not associated with prognostic importance for survival in patients with SCLC.

Effects of treatment regimens on survival in patients with malignant pleural mesothelioma.

BACKGROUND AND OBJECTIVE: In this study, we aimed to investigate the factors affecting the survival of patients with malignant pleural mesothelioma (MPM) according to their treatment regimens, including best supportive care (BSC), chemotherapy, surgical group and multimodality (MM) therapy. PATIENTS: A retrospective analysis was performed on clinical data and treatment outcomes of 400 patients registered in our hospital with MPM between January 1989 and April 2010. RESULTS: Mean age (p < 0.001), presence of asbestos exposure (p = 0.0014), presence of smoking history (p < 0.001), Karnofsky performance status (p < 0.001), histological subtype (p = 0.034) and stage (p < 0.001) variables were found to be significantly different among the four treatment regimens. Mean survival time of all patients was 12.32 months. Mean survival time 10.5 months for the BSC group, 15.7 for the surgical group, 16.02 for the chemotherapy group, and 26.55 for the MM group. There were significant differences in mean survival time among the four treatment regimens. In addition, a significant difference was found in survival time between the two chemotherapy groups (p = 0.032). Mean survival time for cisplatin + gemcitabine was found to be 14.49 months and for cisplatin + pemetrexed, 18.34 months. CONCLUSIONS: The MM group had better survival rates than the other groups. The new chemotherapy combination, cisplatin + pemetrexed, can be helpful in improving survival time.      

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

[Influence of systemic photodynamic therapy on circulating tumor cells in peripheral blood of cancer patients].

The aim of this investigation is to study the number of circulating tumor cells (CTCs) in the blood of cancer patients after systemic photodynamic therapy (PDT) at different times and to assess apoptosis of these cells. The study group consisted of 19 patients with malignant tumors of epithelial origin at various stages (II-IV). CTC identification was performed with flow cytometry by immunophenotype Ep-CAM (CD326)+ CD45-. CTC apoptosis was identified by criteria of plasma membrane integrity and phosphatidylserine translocation on the outer surface of the membrane. Negative correlation between the CTC frequency and apoptotic death rate of these cells was found in patients before the treatment (R = -0.51, p = 0.03). CTC frequency gradually reduced during the first three days after PDT, and then it was maintained at the same level until the end of the follow-up (7 days). At the individual level, the effect of PDT depended on the frequency of CTCs before the treatment: the decrease in these cell frequency occurred significantly more often in the patients with an initially high frequency of CTCs than in other patients (p = 0.05). With the decrease in the CTC frequency, apoptotic death increased within 6 hours after the treatment and remained at the same level until the end of the follow-up period. The results demonstrate the efficacy of systemic PDT for elimination of tumor cells circulating in the peripheral blood of cancer patients with different localization of primary tumor and stage of disease.

Prognostic factors in elderly patients with advanced non-small cell lung cancer treated with first-line cisplatin-based chemotherapy: a retrospective analysis of single institution.

PURPOSE: Non-small cell lung cancer (NSCLC) makes up 80-85% of all lung cancers cases. Lung cancer in older individuals is frequently undertreated. Patients eligible for cisplatin- based chemotherapy should be selected carefully. The aim of this retrospective single-center study was to evaluate prognostic factors for overall survival (OS) in elderly (≥65 years) patients with advanced NSCLC who received first-line cisplatin-based chemotherapy. METHODS: We retrospectively reviewed 110 elderly patients with locally advanced or metastatic NSCLC who had been administered cisplatin-based first-line chemotherapy between December 2004 and November 2011. Seventeen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. RESULTS: Among the 17 variables of univariate analysis, 4 were identified to have prognostic significance for OS: comorbidities (p<0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p=0.02), first-line chemotherapy cycles (p<0.001) and serum albumin level (p=0.04). Multivariate analysis showed that only ECOG PS (p=0.01) was independent prognostic factor for OS. CONCLUSION: PS was important prognostic factor in elderly patients with advanced NSCLC. The findings of this study may facilitate pretreatment prediction of OS and therefore can be used for selecting the most appropriate treatment for elderly patients.

Contribution of low-molecular weight heparin addition to concomitant chemoradiotherapy in the treatment of glioblastoma multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is the most common brain tumor in adults and has a very aggressive course. Median survival is as short as 2 years with standard treatment (chemoradiotherapy followed by adjuvant temozolomide). The purpose of this study was to determine the contribution of low molecular weight heparin (LMWH) addition to concomitant chemoradiotherapy in the treatment of GBM. METHODS: All patients with newly diagnosed GBM between March 2004-May 2009 were evaluated. After surgical intervention (total, subtotal resection or only biopsy) all of them were treated with concomitant chemoradiotherapy (2 Gy daily, 5 days a week, 30 fractions, total tumor dose 60 Gy; and 75 mg/m² temozolomide, 7 days a week), followed by adjuvant temozolomide (6 cycles, 150-200 mg/m², 5 days every 28 days), with or without LMWH (4000 IU/day, 7 days a week, concomitant with radiotherapy) because of risk of thrombosis. The primary endpoint was the determination of progression-free survival (PFS) and overall survival (OS); secondary endpoints were 1- and 2-year OS survival. RESULTS: 30 patients (13 patients in the group non receiving LMWH (LMWH-) and 17 patients in the group receiving LMWH (LMWH+)) were included in the study. Median age was 54 years (range 24-75). Median PFS was 57 and 38 weeks in LMWH+ and LMWH- groups, respectively (p=0.068). Median OS was 69 and 44 weeks (p=0.095), 1-year OS survival 84.6 and 41.2% (p=0.016), and 2-year OS survival 38.5 and 5.9% in LMWH+ and LMWH-, respectively (p=0.061). No significant difference was noted between the two groups for grade 3-4 toxicity (p>0.05). CONCLUSION: Better PFS, OS and 2-year OS survival were obtained in present study with the addition of LMWH to concomitant chemoradiation for GBM but without statistical significance. One-year OS survival was statistically significant favoring the LMWH group. The addition of LMWH did not increase temozolomide toxicity.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Docetaxel and Cisplatin Plus Fluorouracil compared with Modified Docetaxel, Cisplatin, and 5-Fluorouracil as first-line therapy for advanced gastric cancer: a retrospective analysis of single institution.

Gastric cancer is the second most common among cancer-related deaths in the world. Systemic chemotherapy for patients with gastric cancer has limited impact on overall survival. We performed a retrospective analysis of the efficacy and side effects of Docetaxel and Cisplatin Plus Fluorouracil (DCF) versus Modified-Dose Docetaxel, Cisplatin, and 5-Fluorouracil (mDCF) in the metastatic gastric cancer with first-line chemotherapy treated patients. Retrospectively were reviewed 107 locally advanced or metastatic gastric cancer patients who were treated DCF or mDCF as first-line treatment from June 2007 to August 2011 in Dicle University Hospital, Department of Medical Oncology.The DCF protocol included 75 mg/m2 docetaxel and cisplatin on day 1 and 750 mg/m2/day 5-FU infusion for 5 days, repeated every 3 weeks. The mDCF protocol included 60 mg/m² docetaxel and cisplatin on day 1 and 600 mg/m² 5-Fluorouracil continuous infusion per day on days 1-5, every 3 weeks.Patients were treated using DCF arm 85 (M: 56, F: 29), the mDCF arm 22 (M: 13, F: 9) After treatment toxicities were: Grade III-IV neutropenia (48.2% vs 13.6% p=0.003), anemia (21.2% vs 4.5% p=0.06), nausea (44.7% vs 13.6% p=0.008) and vomiting (31.8% vs 4.5%, p=0.01) was higher in the DCF arm. Other toxicities profile was similar in both groups (p>0.05). The rate of response was similar in both arm. Among patients with the DCF and mDCF arm rate complete response (10.3% vs 6.7%, p>0.05), partial response (35.3% vs 40.0%, p>0.05), stable disease (32.4% vs 33.3%, p>0.05), progressive disease (22.1% vs 20.0%, p>0.05) and overall response (45.6% vs 46.7%, p>0.05) did not have a statistically difference (p>0.05). Progression-free survival (PFS) and overall survival (OS) were more favorable in the DCF arm than mDCF arm, but the difference was not significant statistically (9.9 vs 8.6, 7.4 vs 6.5 p>0.05)In conclusion, the response rate, median PFS and median OS are similar in both arms, while the mDCF regimen are more favorable than the DCF for toxicity profile regimen in advanced gastric cancer patients who were undergoing first-line palliative treatment. Therefore, a prospective and larger clinical trials are needed.