Tissue Antioxidant Status and Lipid Peroxidation Are Related to Dietary Intake of n-3 Polyunsaturated Acids: A Rabbit Model.

Polyunsaturated fatty acid (PUFA) metabolism and tissue distribution is modulated by the oxidation of these molecules. This research aimed to investigate the implication of dietary n-3 PUFA supplementation (precursor and long-chain PUFA) on the PUFA profile and oxidative status of the liver, testis, and brain of adult rabbit bucks. Twenty New Zealand White rabbit bucks were divided into four experimental groups (n = 5 per group) and were fed different diets for 110 days: control (CNT), standard diet containing 50 mg/kg alpha-tocopheryl acetate (vitamin E); CNT+, standard diet + 200 mg/kg vitamin E; FLAX, standard diet + 10% flaxseed + 200 mg/kg vitamin E; or FISH, standard diet + 3.5% fish oil + 200 mg/kg vitamin E. Antioxidants (enzymatic and non-enzymatic), oxidative status (malondialdehyde and isoprostanoids), and n-3 and n-6 PUFAs of tissues were analysed. A chain mechanism of oxidant/antioxidant molecules, which largely depended on the particular PUFA composition, was delineated in the different organs. The liver showed an oxidant/antioxidant profile and lipid pathways widely modulated by PUFA and vitamin E administration; on the other hand, the testis' oxidative profile rather than its lipid profile seemed to be particularly affected, an outcome opposite to that of the brain (modulation operated by dietary PUFA).

Cytotoxic Effects of Cannabinoids on Human HT-29 Colorectal Adenocarcinoma Cells: Different Mechanisms of THC, CBD, and CB83.

In this study, we investigated the effects of exposition to IC50 dose for 24 h of a new synthetic cannabinoid (CB83) and of phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) on HT-29 colorectal carcinoma cells. Cell viability and proliferative activity evaluated using the MTT, lactate dehydrogenase (LDH), and CyQUANT assays showed that cell viability was significantly affected when CB83, THC, and CBD were administered to cells. The results obtained showed that the reduced glutathione/oxidized glutathione ratio was significantly reduced in the cells exposed to CBD and significantly increased in the cells treated with the CB83 when compared to the controls. CBD treatment causes a significant increase in malondialdehyde content. The catalase activity was significantly reduced in HT-29 cells after incubation with CB83, THC, and CBD. The activities of glutathione reductase and glutathione peroxidase were significantly increased in cells exposed to THC and significantly decreased in those treated with CBD. The ascorbic acid content was significantly reduced in cells exposed to CB83, THC, and CBD. The ultrastructural investigation by TEM highlighted a significantly increased percentage of cells apoptotic and necrotic after CB83 exposition. The Annexin V-Propidium Iodide assay showed a significantly increased percentage of cells apoptotic after CB83 exposition and necrotic cells after CBD and THC exposition. Our results proved that only CBD induced oxidative stress in HT-29 colorectal carcinoma cells via CB receptor-independent mechanisms and that CB83 caused a mainly CB2 receptor-mediated antiproliferative effect comparable to 5-Fuorouracil, which is still the mainstay drug in protocols for colorectal cancer.

Feasibility of modified docetaxel, oxaliplatin, capecitabine followed by capecitabine as maintenance chemotherapy as first-line therapy for patients with metastatic gastric or gastroesophageal cancer.

The aim of this study was to evaluate the efficacy and safety of modified docetaxel, oxaliplatin, capecitabine (DOC) combination chemotherapy, followed by maintenance capecitabine as first-line therapy for patients with metastatic gastric or gastroesophageal junction (GEJ) cancer. Treatment consisted of docetaxel 35 mg/m (days 1-8), l-OHP 85 mg/m (day 1), and capecitabine 750 mg/m twice daily (days 1-14), every 3 weeks. After six cycles of DOC, patients who did not progress received maintenance treatment with three-weekly capecitabine 1000 mg/m twice daily (days 1-14), until disease progression or unacceptable toxicity. Six-month disease control rate (DCR) was the primary endpoint and overall survival (OS), progression-free survival (PFS) and safety were the secondary endpoints. The Kaplan-Meier method was applied to estimate OS and PFS. Between July 2014 and September 2017, 37 patients with metastatic gastric or GEJ cancer were enrolled at our institution. Upon completion of the DOC regimen, 35 patients (94.5%) received capecitabine as maintenance chemotherapy for a median of 7 cycles (range, 3-14 cycles). The six-month DCR was 83.7% [95% confidence interval (CI), 71.8-95.6%], median PFS was 8.2 months (95% CI, 6.3-9.8 months), and median OS was 14.4 months (95% CI, 11.7-18.6 months). During DOC chemotherapy, the most common grade 3-4 adverse events were neutropenia (29.7%), anemia (10.8%), and diarrhea (10.8%). During maintenance treatment, toxicity was sporadic and mainly of grade 1-2. Modified DOC followed by capecitabine as maintenance chemotherapy seems to be an active and well tolerated first-line treatment strategy for patients with metastatic gastric and GEJ cancer.

Resistin in Human Seminal Plasma: Relationship with Lipid Peroxidation, CAT Activity, GSH/GSSG Ratio, and Semen Parameters.

Resistin is an adipokine involved in inflammation and able to induce the expression of other proinflammatory cytokines. It is known that, in human semen, resistin is correlated with inflammatory cytokines and sperm quality. The aim of this prospective study was to explore the potential relationship between resistin, lipid peroxidation (LPO), catalase (CAT) activity, and reduced and oxidized glutathione (GSH/GSSG) ratio in semen samples of infertile patients with leukocytospermia (no. 19), infertile patients with varicocele (no. 17), and fertile men (no. 17). Semen analysis was performed following the WHO guidelines, and sperm apoptosis and necrosis were evaluated with annexin V/propidium iodide assay. Seminal plasma samples were used to determine resistin levels by an immunological method, MDA concentration by a HPLC analysis with UV detection, GSH/GSSG ratio by an enzymatic method, CAT activity by a spectrophotometric method. The results showed that, in both groups of infertile patients, semen parameters were significantly reduced (P < 0.001) and sperm apoptosis and necrosis percentages were increased. Resistin levels were significantly higher in leukocytospermia and varicocele groups (P < 0.001 and P < 0.01, respectively) as well as MDA concentration (P < 0.001) compared to controls. The MDA level was also significantly increased in the leukocytospermia group versus the varicocele group (P < 0.05). The GSH/GSSG ratio was higher in fertile controls than the leukocytospermia group (P < 0.05) and the varicocele group (P < 0.001) and in the leukocytospermia group versus the varicocele group (P < 0.05). Both the leukocytospermia and varicocele groups showed increased values of CAT activities (P < 0.001) than controls. Briefly, the correlation between variables, calculated in the whole patient population, showed that resistin levels positively correlated with MDA levels, CAT activity, sperm apoptosis, and necrosis and negatively with sperm parameters and GSH/GSSG ratio. These results support an active role of resistin in an inflammatory process causing LPO, increase of CAT activity, and decrease of GSH/GSSG ratio in seminal plasma of infertile men vs. fertile controls.

Capecitabine Plus Oxaliplatin and Bevacizumab, Followed by Maintenance Treatment With Capecitabine and Bevacizumab for Patients Aged > 75 Years With Metastatic Colorectal Cancer.

BACKGROUND: The aim of the present study was to evaluate the efficacy and safety of the combination of CAPOX-Bev (capecitabine [Cap] plus oxaliplatin and bevacizumab [Bev]), followed by maintenance Cap and Bev, for patients with metastatic colorectal cancer (mCRC) and aged > 75 years. PATIENTS AND METHODS: The regimen consisted of intravenous oxaliplatin 130 to 100 mg/m2 on day 1, oral Cap 750 to 1000 mg/m2 twice daily on days 1 to 14, and Bev 7.5 mg/kg on day 1, every 3 weeks. After 4 cycles of CAPOX-Bev, the patients without evidence of disease progression received maintenance treatment with Cap 1000 to 1250 mg/m2 twice daily on days 1 to 14 and Bev 7.5 mg/kg on day 1, every 3 weeks, until disease progression or unacceptable toxicity. The primary endpoint was the 9-month disease control rate. Progression-free survival (PFS), overall survival (OS), and safety were the secondary endpoints. RESULTS: Overall, 36 patients were enrolled from March 2012 to April 2017 at our institution. After completion of CAPOX/Bev, 15 patients (41.7%) had a partial response, 18 (50.0%) had stable disease, and 3 (8.3%) had progressive disease. Thirty-three patients (91.7%) received the Cap/Bev regimen as maintenance treatment for a median of 8.6 cycles (range, 3-14 cycles). The 9-month DCR was 58.3% (95% confidence interval [CI], 40.8-74.5), the median PFS was 8.8 months (95% CI, 6.7-10.3 months), and the median OS was 20.8 months (95% CI, 16.1-25.4 months). With the CAPOX/Bev regimen, the most common grade 3 toxicity included neutropenia (11.1%), diarrhea (5.5%), nausea/vomiting (2.8%), and fatigue (2.8%). Grade 3 neurotoxicity was not observed. With Cap/Bev maintenance therapy, grade 3 hand-foot syndrome was observed in 2 patients (6.0%). CONCLUSION: CAPOX/Bev, followed by Cap/Bev as maintenance treatment, is safe and effective in terms of PFS and OS for elderly patients aged > 75 years with mCRC.

Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy.

BACKGROUND: In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. PATIENTS AND METHODS: Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. RESULTS: Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. CONCLUSION: Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS.

Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review.

Traumatic brain injury (TBI) is one of the world's leading causes of morbidity and mortality among young individuals. TBI applies powerful rotational and translational forces to the brain parenchyma, which results in a traumatic diffuse axonal injury (DAI) responsible for brain swelling and neuronal death. Following TBI, axonal degeneration has been identified as a progressive process that starts with disrupted axonal transport causing axonal swelling, followed by secondary axonal disconnection and Wallerian degeneration. These modifications in the axonal cytoskeleton interrupt the axoplasmic transport mechanisms, causing the gradual gathering of transport products so as to generate axonal swellings and modifications in neuronal homeostasis. Oxidative stress with consequent impairment of endogenous antioxidant defense mechanisms plays a significant role in the secondary events leading to neuronal death. Studies support the role of an altered axonal calcium homeostasis as a mechanism in the secondary damage of axon, and suggest that calcium channel blocker can alleviate the secondary damage, as well as other mechanisms implied in the secondary injury, and could be targeted as a candidate for therapeutic approaches. Reactive oxygen species (ROS)-mediated axonal degeneration is mainly caused by extracellular Ca2+. Increases in the defense mechanisms through the use of exogenous antioxidants may be neuroprotective, particularly if they are given within the neuroprotective time window. A promising potential therapeutic target for DAI is to directly address mitochondria-related injury or to modulate energetic axonal energy failure.

Nitric oxide, malondialdheyde and non-enzymatic antioxidants assessed in viable spermatozoa from selected infertile men.

There are growing evidences that the semen of infertile male population shows higher reactive oxygen species (ROS) levels concomitant with lower antioxidant capacity compared to those detected in semen of fertile population. The plasma membrane of the sperm cell, which has high levels of polyunsaturated fatty acids, renders it particularly sensitive to ROS. The aim of this study was to compare the sperm parameters (concentration, motility, morphology and vitality) and the levels of malondialdehyde (MDA), as marker of lipid peroxidation (LPO), nitric oxide (NO), ascorbic acid (AA), total (GSHt) and oxidized glutathione (GSSG) in viable sperm in a group of 38 infertile patients and in a group of 55 control subjects with unknown reproductive potential. The comparison between variables in infertile patients and controls revealed that the sperm quality was reduced in the infertile group, whereas the levels of NO, AA and GSH were significantly increased in viable spermatozoa from infertile men; however, the endogenous levels of MDA were similar in infertile and control groups. Based on our results, we could speculate that the rise of GSHt and AA levels in viable sperm of infertile group help partially to counteract the damaging effect of ROS and partly prevent a substantial LPO. The observation of the concomitant increase of NO and antioxidant indices in viable spermatozoa of infertile subjects is a novel finding and we think that these results can be useful since the viable sperm population is conceivably used in assisted reproductive technology.

Biofortification with Iron and Zinc Improves Nutritional and Nutraceutical Properties of Common Wheat Flour and Bread.

The effect of field foliar Fe and Zn biofortification on concentration and potential bioavailability of Fe and Zn and health-promoting compounds was studied in wholemeal flour of two common wheat varieties (old vs modern). Moreover, the effect of milling and bread making was studied. Biofortification increased the concentration of Zn (+78%) and its bioavailability (+48%) in the flour of the old variety, whereas it was ineffective in increasing Fe concentration in both varieties. However, the old variety showed higher concentration (+41%) and bioavailability (+26%) of Fe than the modern one. As regard milling, wholemeal flour had higher Fe, Zn concentration and health-promoting compounds compared to white flour. Bread making slightly change Fe and Zn concentration but greatly increased their bioavailability (77 and 70%, respectively). All these results are of great support for developing a production chain of enriched functional bread having a protective role against chronic cardio-vascular diseases.

Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose.

The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these issues, biochemical and immunohistological markers of oxidative/nitrosative stress were evaluated. We found that i-NOS, NOX2 and nitrotyrosine expression were significantly higher in the hearts of subjects who had died from high doses of cocaine, compared to the control group. Increase of these markers was associated with a dramatic increase in 8-OHdG, another marker of oxidative stress. A high number of TUNEL-positive apoptotic myocells was observed in the study group compared to the control group. The immunoexpression of TNF-α was significantly higher in the cocaine group compared to the control group. Furthermore, we detected a significantly stronger immunoresponse to anti-SMAC/DIABLO in our study group compared to control cases. Both cardiac Fas-dependent and mitochondria-dependent apoptotic pathways appeared to be activated to a greater extent in the cocaine group than in the control group. Our results highlight the central role of oxidative stress in cocaine toxicity. High levels of NOS can promote the oxidation process and lead to apoptosis.

Apatinib for the treatment of gastric cancer.

INTRODUCTION: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2, has demonstrated encouraging anti-cancer activity in gastric cancer within both in vitro and in vivo models. AREAS COVERED: Apatinib's efficacy, tolerability and safety have been evaluated in one Phase II and one Phase III study in metastatic/advanced gastric cancer. In this review, we focus on the mechanism of action of apatinib, its pharmacokinetic profile and its clinical activity in the treatment of advanced/metastatic gastric cancer. Expert commentary: Unfortunately, as yet, there is no definitive biomarker data for apatinib in gastric cancer.

Maintenance treatment with oral cyclophosphamide and bevacizumab in patients with recurrent epithelial ovarian cancer.

AIM: To evaluate the efficacy and safety of maintenance treatment with oral cyclophosphamide (Cy) and bevacizumab (Bev) in patients with recurrent ovarian cancer. PATIENTS & METHODS: Induction treatment consisted of cisplatin, epirubicin, Cy and Bev every 3 weeks, for a maximum of six cycles. Maintenance treatment consisted of oral Cy 50 mg, days 1-14 and Bev 15 mg/kg, every 3 weeks until disease progression occurred. RESULTS: In total, 39 patients were enrolled: after induction chemotherapy, the objective response was 74.3%. The median progression-free survival was 13.3 months, and the median overall survival was 33.2 months. Toxicity during maintenance treatment was mild. CONCLUSION: Maintenance with Cy and Bev may achieve encouraging results in terms of progression-free survival and overall survival in recurrent ovarian cancer patients.

Treatment of advanced oesophagogastric cancer with FOLFOX-4 regimen followed by leucovorin/bolus and continuous infusion 5-FU as maintenance chemotherapy in patients aged ≥ 75 years with impaired performance status.

OBJECTIVES: To evaluate the efficacy and safety of FOLFOX-4 combination chemotherapy, followed by leucovorin (LV)/bolus and continuous infusion 5-fluorouracil (5-FU) as maintenance chemotherapy in elderly (≥ 75 years) patients with advanced oesophagogastric cancer with impaired performance status (PS). MATERIALS AND METHODS: Patients with a PS score >1 were included in this study. PS evaluations were performed by a geriatrician and two medical oncologists. FOLFOX-4 consisted of oxaliplatin concurrently with LV/bolus and continuous infusion 5-FU every 2 weeks. After a maximum of six FOLFOX-4 cycles, patients with no evidence of disease progression received maintenance treatment with LV/bolus and continuous infusion 5-FU every 2 weeks until disease progression or unacceptable toxicity. RESULTS: Thirty-eight patients were enrolled in this study. Of these, 32 (84.2%) patients had a PS score of 2 and six (15.7%) patients had a PS score of 3. After completion of FOLFOX-4, 18 (47.3%) patients achieved a partial response and 14 (36.8%) patients had stable disease. Thirty-two patients (84.2%) received maintenance chemotherapy for a median of eight cycles (range one to 26 cycles). The 6-month disease-control rate was 47.3% [95% confidence interval (CI) 30.9-64.1]. The median progression-free survival was 5.9 months (95% CI 4.7-6.8) and the median overall survival was 9.6 months (95% CI 8.1-11.7). Grade 3 neutropenia occurred in six patients (15.7%), and Grade 3 anaemia and thrombocytopenia occurred in two patients (5.2%). CONCLUSION: FOLFOX-4 followed by LV/bolus and continuous infusion 5-FU as maintenance chemotherapy seems to be an active and well-tolerated first-line treatment strategy for elderly patients with advanced oesophagogastric cancer and impaired PS.

Role of chemotherapy in the treatment of metastatic castration-resistant prostate cancer patients who have progressed after abiraterone acetate.

Abiraterone acetate is a novel irreversible inhibitor of CYP17 that was recently approved for men with post-chemotherapy or chemo-naive castration-resistant prostate cancer. Unfortunately, this agent is not curative, and patients often ultimately develop resistance. However, men who progress after treatment with this new hormonal agent may be considered for another line of chemotherapy-based treatment. In 2004, docetaxel (D) and prednisone were found to improve survival compared with older regimens. More recently, cabazitaxel (C), a novel taxane chemotherapy, has been found to prolong survival in patients who exhibit disease progression during or after D chemotherapy. Here, we review the first clinical studies in which castration-resistant prostate cancer patients received chemotherapy with D or C after progression during abiraterone acetate treatment.

Carboplatin, methotrexate, vinblastine, and epirubicin (M-VECa) as salvage treatment in patients with advanced bladder cancer: a phase II study.

The primary objective of this study was to determine the activity and safety of carboplatin, methotrexate, vinblastine, and epirubicin (the M-VECa regimen) in patients with advanced bladder cancer after failure of at least one chemotherapy line. Treatment consisted of carboplatin 250 mg/m on day 1, methotrexate 30 mg/m on days 1 and 22, vinblastine 3 mg/m on days 2 and 22, and epirubicin 50 mg/m on day 2 every 28 days until disease progression or death. Response rate was the main end-point. Twenty-five patients were enrolled: the median age was 67 years (range 42-83) and there were 14 patients aged at least 70 years (56%). Fourteen patients had previously received vinflunine as a second-line treatment. Complete remission occurred in one patient (4%), partial remission in five patients (20%), and stable disease in eight patients (32%). The overall response rate was 24% [95% confidence interval (CI), 9.3-45.1%] and the overall disease control rate was 56% (95% CI, 34.9-75.5%). The median progression-free survival was 5.1 months (95% CI, 3.9-6.4) and the median overall survival was 9.5 months (95% CI, 7.1-11.2). Treatment was well tolerated: grade 3 neutropenia was documented in five patients and grade 3 nausea and vomiting in two patients. The M-VECa regimen seems to be feasible as second-line or third-line treatment in patients with advanced bladder cancer who have been pretreated with one or more chemotherapy lines, and may achieve encouraging results in terms of disease control rate, progression-free survival, and overall survival.

Reduced Dose of Abiraterone Acetate with Concomitant Low-dose Prednisone in the Treatment of ≥ 85 Year-old Patients with Advanced Castrate-resistant Prostate Cancer.

AIM: The aim of the study was to evaluate the activity and safety of reduced-dose abiraterone acetate (AA) in ≥ 85 year-old patients with advanced castrate-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Patients received 750 mg oral AA as three 250-mg tablets once daily, with concomitant oral prednisone, 5 mg daily. RESULTS: Twenty-six patients were enrolled; median age was 88 years (range=85-93). Prostate-specific antigen (PSA) response was observed in 18 (69.2%) subjects, median time to PSA progression was 6.4 months (95% confidence interval (CI)=2.8-8.8) and median overall survival was 14.3 months (95% CI=7.2-18.3). The treatment was well-tolerated and adverse events, related to mineralocorticoid excess, were of grade 1-2 in all patients. CONCLUSION: Reduced dose of AA combined with a very low dose of prednisone is effective and well-tolerated in very elderly patients with advanced CRPC.

Targeted Therapies for Prostate Cancer.

New therapies for prostate cancer have emerged over the past three years. Nevertheless, none of these agents is curative, and unfortunately, patients often ultimately develop resistance to these agents. Therefore, the development of innovative and effective therapies that overcome these resistances is necessary. Unfortunately, the results of a phase III trial evaluating docetaxel in combination with targeted therapies demonstrated no difference in survival. Moreover, scarce data on the combination of a targeted therapy with new agents are currently available. New trials are investigating these possible combination treatments; the results of these (on-going) clinical studies are awaited.

Sequential treatment with epirubicin, oxaliplatin and 5FU (EOF) followed by docetaxel, oxaliplatin and 5FU (DOF) in patients with advanced gastric or gastroesophageal cancer: a single-institution experience.

PURPOSE: The aim of this study was to evaluate the activity and safety of epirubicin (EPI), oxaliplatin (l-OHP) and 5fluorouracil (5FU) (EOF) followed by docetaxel (D), l-OHP and 5FU (DOF) in patients with advanced gastric or gastroesophageal junction (GEJ) cancer. METHODS: Forty-five patients were enrolled: 26 gastric and 19 GEJ cancer. Median age was 69 years (range 34-83); ECOG performance status was 0-1 in 37 patients. Treatment consisted of EPI 50 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (EOF), every 3 weeks for a maximum of 4 cycles. After EOF completion, patients received D 70 mg/m(2) combined with l-OHP 130 mg/m(2) on day 1 and continuous infusion 5FU 750 mg/m(2) days 1-5 (DOF), every 3 weeks for a maximum of 4 cycles. RESULTS: After sequential EOF/DOF, the overall response rate was 51.1 % (95 % CI 35.7-66.2 %) and 93.3 % of patients were progression free 6 months after the onset of chemotherapy. The median progression-free survival was 9.5 months (95 % CI 8.0-11.9 months), and the median overall survival was 15.8 months (95 % CI 13.6-18.9 months). Grade 3 neutropenia was observed in 15 patients (33.3 %) after sequential EOF/DOF. CONCLUSIONS: The sequential treatment EOF/DOF is feasible in well-selected patients with advanced gastric or GEJ cancer and shows encouraging survival results.

Switch maintenance treatment with oral vinorelbine and bevacizumab after induction chemotherapy with cisplatin, gemcitabine and bevacizumab in patients with advanced non-squamous non-small cell lung cancer: a phase II study.

The present study evaluated the efficacy and safety of cisplatin (Cis), gemcitabine (Gem) and bevacizumab (Bev), followed by maintenance treatment with Bev and oral vinorelbine (Vnb), in patients with advanced non-squamous non-small cell lung cancer (NSCLC). The patients were administered six cycles of induction chemotherapy consisting of intravenously (i.v.) Cis 70 mg/m(2) on day 1 plus i.v. Gem 1000 mg/m(2) on days 1 and 8, plus i.v. Bev 7.5 mg/kg on day 1, every 3 weeks. Patients who did not experience tumor progression remained on maintenance treatment with Bev combined with oral Vnb 60 mg/m(2) weekly until occurrence of disease progression or unacceptable toxicity. Thirty-seven patients were enrolled: The median age was 67 years (range 38-81); 22 patients were male, and 30 patients had stage IV tumors. The response rate was 32.4 % (95 % CI 18-49.7). The 9-month disease-control rate was 45.9 %. The median PFS was 8.4 months (95 % CI 4.4-10.7), and the median OS was 18.1 months (95 % CI 15.3-20.8 months). Grade 3-4 neutropenia occurred in 6 (16.2 %) patients and grade 3-4 thrombocytopenia in four (10.8 %) patients during induction chemotherapy. Bev- or Vnb-associated toxicities were mild. Switch maintenance treatment with Bev and oral Vnb after first-line Cis, Gem and Bev is feasible in patients with non-squamous NSCLC and may achieve encouraging results in terms of PFS and OS.

Gemcitabine, oxaliplatin, and capecitabine (GEMOXEL) compared with gemcitabine alone in metastatic pancreatic cancer: a randomized phase II study.

BACKGROUND: Single-agent gemcitabine (GEM) has been considered for many years as the standard first-line treatment for advanced pancreatic cancer. However, recently, several studies reported encouraging activity and good tolerability for some combination regimens. Considering the apparently non-overlapping toxicity and the proved individual efficacy of GEM, oxaliplatin (L-OHP), and capecitabine (CAP), this randomized phase II study compared the activity and safety of the combination GEM, L-OHP, and CAP (GEMOXEL) versus GEM alone, in patients with metastatic pancreatic cancer. MATERIALS AND METHODS: The treatment in GEMOXEL arm consisted of GEM 1,000 mg/m(2) as a 30-min intravenous infusion on days 1, 8, 15, 22, L-OHP 100 mg/m(2) i.v. on day 2, and CAP 1,500 mg/m(2)/day in two divided doses on days 1-14, every 21 days (one cycle). In both treatment groups, GEM was administered weekly for seven consecutive weeks followed by 1-week rest for the first 8 weeks, and thereafter, GEM was continued on days 1, 8, 15, every 28 days. Chemotherapy was administered until disease progression or unacceptable toxicity. RESULTS: Sixty-seven patients were enrolled in the study. Thirty-four were randomly assigned to GEMOXEL and 33 to GEM. At 4 months, disease control rate was 79.4% with GEMOXEL versus 45.4 % with GEM (p = 0.004). The median progression-free survival was 6.8 months (95% CI 5.3-7.3 months) in GEMOXEL arm and 3.7 months (95% CI 2.9-4.7 months) in GEM arm (p < 0.001). The median OS was 11.9 months (95% CI 10.6-12.9 months) in GEMOXEL arm and 7.1 months (95% CI 5.5-9.1 months) in GEM arm (p < 0.001). Hematologic and non-hematologic toxicity was more severe with combination chemotherapy, yet still tolerable. No grade 4 adverse events were observed with either regimen. CONCLUSION: GEMOXEL regimen seemed to be safe and more efficient than the standard therapy with GEM alone in the treatment of metastatic pancreatic cancer.