Axitinib dose titration: analyses of exposure, blood pressure and clinical response from a randomized phase II study in metastatic renal cell carcinoma.

Background: In a randomized, double-blind phase II trial in patients with metastatic renal cell carcinoma (mRCC), axitinib versus placebo titration yielded a significantly higher objective response rate. We evaluated pharmacokinetic and blood pressure (BP) data from this study to elucidate relationships among axitinib exposure, BP change, and efficacy.

Patients And Methods: Patients received axitinib 5 mg twice daily during a lead-in period.

A phase 3 randomized, double-blind, placebo-controlled trial of ganitumab or placebo in combination with gemcitabine as first-line therapy for metastatic adenocarcinoma of the pancreas: the GAMMA trial.

Background: This double-blind, phase 3 study assessed the efficacy and safety of ganitumab combined with gemcitabine as first-line treatment of metastatic pancreatic cancer.

Patients And Methods: Patients with previously untreated metastatic pancreatic adenocarcinoma were randomly assigned 2 : 2 : 1 to receive intravenous gemcitabine 1000 mg/m(2) (days 1, 8, and 15 of each 28-day cycle) plus placebo, ganitumab 12 mg/kg, or ganitumab 20 mg/kg (days 1 and 15 of each cycle). The primary end point was overall survival (OS).

Efficacy of sunitinib in patients with metastatic or unresectable renal cell carcinoma and renal insufficiency.

Aim: The aim of this retrospective, registry-based study was to analyse treatment outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib and renal insufficiency (RI).

Methods: The cohort included 790 patients treated with sunitinib between 2006 and 2013. At the start of sunitinib therapy 22, 234, and 534 patients had severe (glomerular filtration rate [GFR] <30ml/min/1.

The role of cytochromes p450 and aldo-keto reductases in prognosis of breast carcinoma patients.

Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients. Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients.

Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study.

Background: HannaH (NCT00950300) was a phase III, randomized, international, open-label study that compared pharmacokinetics (PK), efficacy, and safety of two different trastuzumab formulations [subcutaneous (s.c.) and intravenous (i.

Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial.

Background: Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part).

Prognostic significance of CD3+ tumor-infiltrating lymphocytes in patients with endometrial carcinoma.

Aim: The aim of the present study was to investigate tumor-infiltrating leukocytes in patients with endometrial carcinoma.

Patients And Methods: Cluster of differentiation (CD)3(+), CD8(+) and C20(+) tumor-infiltrating lymphocytes (TILs) and CD68(+) tumor-associated macrophages (TAMs) were evaluated retrospectively by immunohistochemistry in tumor specimen from 124 patients with endometrial carcinoma.

Results: A significant decrease of CD3(+) TILs and an increase of CD68(+) TAM count was associated with higher tumor stage.

Oral ridaforolimus plus trastuzumab for patients with HER2+ trastuzumab-refractory metastatic breast cancer.

Background: Although trastuzumab-containing therapies prolong survival in patients with metastatic breast cancer (MBC), most tumors develop trastuzumab resistance, potentially mediated by aberrant phosphatidylinositide 3-kinase (PI3K)/AKT signaling. Ridaforolimus (a mammalian target of rapamycin [mTOR] inhibitor) may overcome trastuzumab resistance by inhibiting PI3K signaling.

Methods: A single-arm, phase IIb trial was conducted to evaluate the efficacy and safety of ridaforolimus-trastuzumab in human epidermal growth factor receptor 2-positive (HER2(+)) trastuzumab-refractory MBC (NCT00736970).

Non-coding polymorphisms in nucleotide binding domain 1 in ABCC1 gene associate with transcript level and survival of patients with breast cancer.

Objectives: ATP-Binding Cassette (ABC) transporters may cause treatment failure by transporting of anticancer drugs outside of the tumor cells. Multidrug resistance-associated protein 1 coded by the ABCC1 gene has recently been suggested as a potential prognostic marker in breast cancer patients. This study aimed to explore tagged haplotype covering nucleotide binding domain 1 of ABCC1 in relation with corresponding transcript levels in tissues and clinical phenotype of breast cancer patients.

Prevalence of perfusion defects detected by stress 99mtechnetium sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with breast cancer.

Aim: The aim of the present study was to investigate myocardial perfusion in relation to disease history and laboratory parameters of atherosclerosis risk in asymptomatic patients with breast carcinoma.

Patients And Methods: One-hundred and eighty-one patients with breast carcinoma were studied. Myocardial perfusion was assessed using single-photon emission computed tomography (SPECT) with 99mtechnetium sestamibi.

Efficacy of everolimus in second- and third-line therapy for metastatic renal cell carcinoma: a registry-based analysis.

Objectives: The aim of the present study was to describe the efficacy and safety of everolimus in the treatment of metastatic renal cell carcinoma (mRCC) after administration of 1 vs. 2 prior tyrosine kinase inhibitors (TKIs).

Patients And Methods: A national renal information system database was used as the data source for the retrospective study.

Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial.

Background: An unmet medical need exists for patients with metastatic renal cell carcinoma who have progressed on VEGF-targeted and mTOR-inhibitor therapies. Fibroblast growth factor (FGF) pathway activation has been proposed as a mechanism of escape from VEGF-targeted therapies. Dovitinib is an oral tyrosine-kinase inhibitor that inhibits VEGF and FGF receptors.

Clinical and laboratory prognostic factors in patients with metastatic renal cell carcinoma treated with sunitinib and sorafenib after progression on cytokines.

Objectives: The aim of this retrospective study was to analyze prognostic factors in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors (TKIs) sunitinib or sorafenib after progression on cytokine therapy.

Materials And Methods: A national database of patients treated with targeted agents was used as the data source. A total of 319 patients treated with sunitinib (n = 181) or sorafenib (n = 138) after progression on cytokine therapy were analyzed.

Human equilibrative nucleoside transporter 1 (hENT1): do we really have a new predictive biomarker of chemotherapy outcome in pancreatic cancer patients?

Although systemic chemotherapy significantly improves the overall survival of pancreatic cancer patients, the prognosis remains extremely poor. The development of a drug resistance, either de novo or induced resistance, significantly limits the effectiveness of chemotherapy. SLC29A1 gene encodes human equilibrative nucleoside transporter 1 (hENT1) protein that is mediating the transport of nucleotides, both purines and pyrimidines, into the tumor cells.

Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.

Background: Vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2)-mediated signalling and angiogenesis can contribute to the pathogenesis and progression of gastric cancer. We aimed to assess whether ramucirumab, a monoclonal antibody VEGFR-2 antagonist, prolonged survival in patients with advanced gastric cancer.

Methods: We did an international, randomised, double-blind, placebo-controlled, phase 3 trial between Oct 6, 2009, and Jan 26, 2012, at 119 centres in 29 countries in North America, Central and South America, Europe, Asia, Australia, and Africa.

A multinational phase II trial of bevacizumab with low-dose interferon-α2a as first-line treatment of metastatic renal cell carcinoma: BEVLiN.

Background: Avastin and Roferon in Renal Cell Carcinoma (AVOREN) demonstrated efficacy for bevacizumab plus interferon-α2a (IFN; 9 MIU tiw) in first-line metastatic renal cell carcinoma (mRCC). We evaluated bevacizumab with low-dose IFN in mRCC to determine whether clinical benefit could be maintained with reduced toxicity.

Methods: BEVLiN was an open-label, single-arm, multinational, phase II trial.

Upside-down stomach - results of mini-invasive surgical therapy.

Aim: The authors evaluate the results of mini-invasive therapy in patients diagnosed with upside-down stomach.

Material And Methods: From 1998 to 2008, a total of 27 patients diagnosed with upside-down stomach were surgically treated at the 1st Department of Surgery, University Hospital Olomouc. Before the operation, patients were examined endoscopically and a barium swallow was performed.

Bevacizumab in combination with IFN-α in metastatic renal cell carcinoma: the AVOREN trial.

Metastatic renal cell carcinoma (mRCC) is tumor resistant to all cytotoxic agents. During the last decade, effective targeted therapies emerged including sunitinib, pazopanib and the combination of bevacizumab with IFN-α. The use of bevacizumab plus IFN-α combination in mRCC is supported by the AVOREN trial.

Metastases of esophageal carcinoma to skeletal muscle: single center experience.

Metastases of esophageal carcinoma to the skeletal muscle are rare, but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography (PET/CT). A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases. Four patients had skeletal muscle metastases of esophageal carcinoma, including two patients with squamous cell carcinoma.

Carotid intima-media thickness and laboratory parameters of atherosclerosis risk in patients with breast cancer.

Aim: To investigate the relation between intima-media thickness (IMT) and laboratory parameters of atherosclerosis risk in patients with breast carcinoma.

Patients And Methods: IMT and a panel of laboratory parameters associated with the risk of atherosclerosis were studied in 192 patients with histologically-verified breast carcinoma.

Results: Patients with metastatic disease had significantly higher fibrinogen, C-reactive protein (CRP), urinary neopterin and mean IMT, and significantly lower serum albumin and hemoglobin concentrations.

Laboratory medicine and medical oncology: the tale of two Cinderellas.

Cancer represents a leading cause of death in the developed countries. The past 50 years have witnessed major progress in both laboratory medicine and clinical oncology that has translated into improved prognosis of cancer patients. From the humble beginnings as unrelated specialties, major advances in the understanding of molecular bases of cancer progression led to increased interactions between laboratory medicine and clinical (mostly medical) oncology.

Skin toxicity and efficacy of sunitinib and sorafenib in metastatic renal cell carcinoma: a national registry-based study.

Background: A retrospective, registry-based analysis to assess the outcomes of metastatic renal cell cancer (mRCC) patients treated with sunitinib and sorafenib who developed dermatologic adverse events was performed.

Patients And Methods: Data on mRCC patients treated with sunitinib or sorafenib were obtained from the Czech Clinical Registry of Renal Cell Cancer Patients. Outcomes of patients who developed hand-foot syndrome (HFS) of any grade and/or grade 3/4 rash during the treatment were compared with patients without HFS and no, mild, or moderate rash.

Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis.

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically.

Hypomagnesaemia in patients with metastatic colorectal carcinoma treated with cetuximab.

Background/aims: Cetuximab is a chimeric antibody registered for the therapy of advanced colorectal carcinoma. Among the side-effects of cetuximab hypomagnesaemia has been described, but the information is still limited.

Methodology: We have evaluated retrospectively serum magnesium, potassium, calcium, creatinine and albumin in 51 consecutive patients with metastatic colorectal carcinoma treated with cetuximab, mostly combined with irinotecan-based combination chemotherapy.