Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases.

Background: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.

Methods: Eighty patients with BM from HER2-positive breast cancer were identified.

Pilot study on sex hormone levels and fertility in women with malignant gliomas.

The standard treatment of patients with high-grade gliomas based on conformal radiation therapy (RT) with or without chemotherapy (CT) may induce endocrine deficiencies of pituitary and subsequently also of peripheral hormones. In 24 premenopausal women with high-grade gliomas treated with RT and CT, hormonal changes and their impact on quality of life were investigated. Serum concentrations of gonadal, pituitary and of thyroid hormones were measured at various time points after initial anti-neoplastic therapy.

Bevacizumab treatment for advanced breast cancer.

Significant advances in the treatment of patients with breast cancer have been made in the past 10 years. The current systemic treatment of breast cancer is characterized by the discovery of multiple cancer targets leading to treatments that are more sophisticated and specific than conventional cytotoxic chemotherapy. Two classes of compounds that have helped improve clinical outcomes are small molecules and monoclonal antibodies targeting specific tyrosine kinase receptors.

Third CECOG consensus on the systemic treatment of non-small-cell lung cancer.

The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137).

The role of fibrinogen plasma levels, the -455G>A fibrinogen and the factor XIII A subunit (FXIII-A) Val34Leu polymorphism in cancer-associated venous thrombosis.

Venous thromboembolism (VTE) is a life-threatening complication in cancer patients. Identification of risk factors has been in focus in the past years. Functional single nucleotide polymorphisms (SNP) of coagulation factors known to influence the concentration or function may be considered to influence the risk of VTE in cancer patients.

Her-2/neu gene amplification and over-expression in stomach and esophageal adenocarcinoma: from pathology to treatment.

Discovery of the over-expression of Her-2/neu or the amplification of its regulatory gene in stomach and esophageal cancer has resulted in targeted treatment directed at this protein. The fact itself and its consequences have been the topic of an abundance of studies and clinical trials. In the present report we review the current state of the art as regards diagnosis of the over-expression and amplification of Her-2/neu, its inhibition as a new therapeutic concept, treatment toxicity, and the development of resistance to Her-2/neu as a limiting factor in stomach and esophageal adenocarcinoma.

Trastuzumab beyond progression: overall survival analysis of the GBG 26/BIG 3-05 phase III study in HER2-positive breast cancer.

Background: Continuation of trastuzumab plus capecitabine (XH) showed a significantly improved overall response rate and time to progression compared with capecitabine (X) alone in women with HER2-positive breast cancer progressing during trastuzumab treatment. Here, we report the final analysis on overall survival.

Patients And Methods: Patients with HER2-positive, advanced breast cancer who progressed during treatment with trastuzumab with or without 1st-line metastatic chemotherapy were prospectively randomised to X (2500mg/m(2) on days 1-14, q3w) or XH (6 (8)mg/kg, q3w).

Safety and efficacy of temsirolimus in heavily pretreated patients with metastatic renal cell carcinoma.

Background: First line treatment with temsirolimus is considered standard of care in poor risk patients with metastatic renal cell carcinoma. The role of temsirolimus in pretreated patients with any risk profile is unclear. The aim of this retrospective analysis was to investigate the impact of temsirolimus in patients who had progressed on various treatment lines.

Comparative susceptibility of Deschutes River, Oregon, Tubifex tubifex populations to Myxobolus cerebralis.

Dams along the Deschutes River (DR) in central Oregon have blocked fish migration for over 40 years. Reestablishment of anadromous fish runs above the dams as part of a fish passage plan may introduce fish pathogens, such as Myxobolus cerebralis, the myxozoan parasite that causes salmonid whirling disease. This parasite is carried by adult salmon that stray into the DR system during their return to enzootic areas of the upper Columbia River basin, and it is now known to be established in at least one lower DR tributary.

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma.

Background: Bortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations.

Design And Methods: The activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma.

Evaluating the impact of Relative Total Dose Intensity (RTDI) on patients' short and long-term outcome in taxane- and anthracycline-based chemotherapy of metastatic breast cancer- a pooled analysis.

Background: Chemotherapy dose delay and/or reduction lower relative total dose intensity (RTDI) and may affect short- and long-term outcome of metastatic breast cancer (MBC) patients.

Methods: Based on 933 individual patients' data of from 3 randomized MBC trials using an anthracycline and taxane we examined the impact of RTDI on efficacy and determined the lowest optimal RTDI for MBC patients.

Results: Median time to disease progression (TTDP) and overall survival (OS) of all patients were 39 and 98 weeks.

Prediction of venous thromboembolism in patients with cancer by measuring thrombin generation: results from the Vienna Cancer and Thrombosis Study.

Purpose: Patients with cancer are at increased risk of venous thromboembolism (VTE). Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE.

Dissecting the human immunologic memory for pathogens.

Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells.

Treatment-by-histology interaction analyses in three phase III trials show superiority of pemetrexed in nonsquamous non-small cell lung cancer.

Introduction: Recently, histology has emerged as a predictive factor for pemetrexed efficacy in non-small cell lung cancer (NSCLC). These analyses evaluate whether the differential efficacy of pemetrexed by NSCLC histology is reproducible and consistent across three registration studies of different lines of therapy (first-line/second-line and maintenance settings).

Methods: The reported studies for patients with advanced NSCLC were pemetrexed versus docetaxel in previously treated patients (N = 571), cisplatin plus pemetrexed versus cisplatin plus gemcitabine in chemotherapy-naive patients (N = 1725), and maintenance pemetrexed plus best supportive care versus placebo plus best supportive care (N = 663).

2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours.

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival.

Capecitabine and Vinorelbine as an All-Oral Chemotherapy in HER2-Negative Locally Advanced and Metastatic Breast Cancer.

BACKGROUND: The oral formulation of vinorelbine together with capecitabine allows for an all-oral combination chemotherapy which promises to raise quality of life of patients with advanced breast cancer. PATIENTS AND METHODS: Patients with HER2-negative, locally advanced, inoperable or metastatic breast cancer were included in this prospective observational trial (treatment schedule: capecitabine 500 mg/m2 twice daily, days 1-14; vinorelbine 60 mg/m2, days 1+8; repeated in 3-week cycles). RESULTS: All 32 patients (median age 50 years) were evaluable for toxicity, and 30 patients for response.

The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells.

Resistance against first and second generation (irreversible) ErbB inhibitors is an unsolved problem in clinical oncology. The purpose of this study was to examine the effects of the irreversible ErbB inhibitors pelitinib and canertinib on growth of breast and ovarian cancer cells. Although in vitro growth-inhibitory effects of both drugs exceeded by far the effects of all reversible ErbB blockers tested (lapatinib, erlotinib, and gefitinib), complete growth inhibition was usually not reached.

Circulating procoagulant microparticles in cancer patients.

Accumulating evidence indicates that microparticles (MPs) are important mediators of the interaction between cancer and the hemostatic system. We conducted a large prospective cohort study to determine whether the number of circulating procoagulant MPs is elevated in cancer patients and whether the elevated MP levels are predictive of occurrence of venous thrombembolism (VTE). We analyzed plasma samples of 728 cancer patients from the ongoing prospective observational Vienna Cancer and Thrombosis Study.

Intensified adjuvant IFADIC chemotherapy in combination with radiotherapy versus radiotherapy alone for soft tissue sarcoma: long-term follow-up of a prospective randomized feasibility trial.

Adjuvant chemotherapy for grade 2 and 3 soft tissue sarcoma (STS) patients still has to be considered experimental. Fifty-nine patients underwent primary surgery by wide or marginal excision and were subsequently randomized to receive radiotherapy alone or in combination with six courses of chemotherapy consisting of ifosfamide, DTIC, and doxorubicin administered in 14-day intervals supported by G-CSF on days 5-13. Twenty-eight patients received radiotherapy (control group) and 31 patients were treated with additional chemotherapy.

Thrombosis risk and survival in cancer patients with elevated C-reactive protein.

Background: The incidence of venous thromboembolism (VTE) is increased among cancer patients.

Objective: We assessed serum levels of C-reactive protein (CRP) in order to study their prognostic significance for VTE and survival in the prospective observational Cancer and Thrombosis Study (CATS).

Patients And Methods: This study includes patients with recently diagnosed cancer or progression of disease after remission.

Hypothyroidism in patients with renal cell carcinoma: blessing or curse?

Background: Sunitinib and sorafenib are tyrosine kinase inhibitors that have important antitumor activity in metastatic renal cell carcinoma (mRCC). Hypothyroidism constitutes a commonly reported side effect of both drugs, and particularly of sunitinib. The objective of this analysis was to investigate whether the occurrence of hypothyroidism during treatment with sunitinib and sorafenib affects the outcome of patients with mRCC.

Prediction of venous thromboembolism in cancer patients.

The risk of venous thromboembolism (VTE) is increased in cancer patients. To improve prediction of VTE in cancer patients, we performed a prospective and observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. A previously developed risk scoring model for prediction of VTE that included clinical (tumor entity and body mass index) and laboratory (hemoglobin level and thrombocyte and leukocyte count) parameters was expanded by incorporating 2 biomarkers, soluble P-selectin, and D-Dimer.

Efficacy of the combination of bortezomib and dexamethasone in systemic AL amyloidosis.

Bortezomib-dexamethasone (Btz/Dex) is an active regimen in patients with multiple myeloma and has been used in few patients with amyloidosis. Here, we report a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis (AL). Eighteen patients (69%) received Btz/Dex as first-line treatment.

Extracerebral metastases determine the outcome of patients with brain metastases from renal cell carcinoma.

Background: In the era of cytokines, patients with brain metastases (BM) from renal cell carcinoma had a significantly shorter survival than patients without. Targeted agents (TA) have improved the outcome of patients with metastatic renal cell carcinoma (mRCC) however, their impact on patients with BM is less clear. The aim of this analysis was to compare the outcome of patients with and without BM in the era of targeted agents.

NeoGemOx: Gemcitabine and oxaliplatin as neoadjuvant treatment for locally advanced, nonmetastasized pancreatic cancer.

Background: Neoadjuvant chemotherapy can facilitate pancreatic resection in patients with initially unresectable pancreatic cancer (PC). We report the results of a phase II trial of gemcitabine-oxaliplatin neoadjuvant chemotherapy for patients with locally advanced, nonmetastatic PC.

Methods: A prospective, phase II clinical trial using neoadjuvant chemotherapy, consisting of gemcitabine (900 mg/m(2)) and oxaliplatin (60 mg/m(2)) given as intravenous infusion once a week at day 1 of each treatment cycle (NeoGemOx protocol).