Pasotuxizumab, a BiTE immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings.

 We report results of a first-in-human study of pasotuxizumab, a PSMA bispecific T-cell engager (BiTE) immune therapy mediating T-cell killing of tumor cells in patients with advanced castration-resistant prostate cancer. We assessed once-daily subcutaneous (SC) pasotuxizumab. All SC patients developed antidrug antibodies; therefore, continuous intravenous (cIV) infusion was assessed.

Basket trials: From tumour gnostic to tumour agnostic drug development.

Molecular profiling provides the insight that specific genetic alterations can be detected across a wide range of different histologically characterised tumour types. Thus, the basic concept of basket trials (BTs) to target those genetic alterations with the same anti-tumour agents independent of the underlying tumour type was tumour agnostic. BTs can be divided into tumour gnostic, tumour semi-gnostic, and tumour agnostic trials which cover BTs of the conventional and the complex multiple-parallel type.

A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer.

Purpose: This phase 1b study investigated the maximum tolerated dose (MTD; primary objective), safety, pharmacokinetics, and antitumor activity (secondary objectives) of eribulin combined with carboplatin in patients with solid tumors and, in particular, non-small cell lung cancer (NSCLC).

Methods: Two dose-escalation schemes were evaluated with carboplatin, at an area under the curve (AUC) of either 5 or 6 mg/mL·min. Eribulin, dose-escalated from 0.

Phase Ib trial combining capecitabine, erlotinib and bevacizumab in pancreatic adenocarcinoma - REBECA trial.

Background Purpose of this phase Ib trial was to establish the maximum tolerable dose (MTD) of capecitabine and to escalate the dosages of erlotinib and bevacizumab to determine the recommended phase II dose (RP2D) in patients with advanced/metastatic pancreatic adenocarcinoma not pretreated for metastatic disease. Methods Starting doses were capecitabine 500 mg/m bid orally continuously, erlotinib 100 mg orally daily, and bevacizumab 5 mg/kg intravenously q 2 weeks. Dose escalation was performed according to a 3 + 3 design for capecitabine until MTD, for erlotinib and bevacizumab until the maximum doses registered by applying a substance-related, toxicity-based scheme accompanied by pharmacokinetic analysis.

Efficacy of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Inhibitor, in Patients with Previously Treated Advanced Urothelial Carcinoma with Alterations.

BGJ398, a potent and selective pan-FGFR antagonist, was prospectively evaluated in patients with metastatic urothelial carcinoma bearing a diverse array of alterations. Patients ( = 67) who were unable to receive platinum chemotherapy were enrolled. The majority (70.

Monitoring of erlotinib in pancreatic cancer patients during long-time administration and comparison to a physiologically based pharmacokinetic model.

Purpose: In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico.

Methods: Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.

Comparing Neoadjuvant Nab-paclitaxel vs Paclitaxel Both Followed by Anthracycline Regimens in Women With ERBB2/HER2-Negative Breast Cancer-The Evaluating Treatment With Neoadjuvant Abraxane (ETNA) Trial: A Randomized Phase 3 Clinical Trial.

Importance: Studies of neoadjuvant chemotherapy regimens using anthracyclines followed by taxanes have reported a doubling of pathological complete remission (pCR) rates compared with anthracycline-based regimens alone. A reverse sequence did not reduce activity. Nab-paclitaxel is an albumin-bound nanoparticle of paclitaxel that allows for safe infusion without premedication, and its use led to a significantly higher rate of pCR in the GeparSepto trial.

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live.

Assessment of Pharmacokinetic Interaction Between Capecitabine and Cetuximab in Metastatic Colorectal Cancer Patients.

Aim: This study focuses on the plasma disposition and metabolic activation of capecitabine (CCB) when administered alone or when combined with cetuximab (CTX).

Patients And Methods: Twenty-four chemo-naïve patients with KRAS wild-type colorectal cancer were randomized into two arms and received either CCB alone (1,000 mg/m(2) bid p.o.

Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial.

There is increasing evidence that breast cancer evolves over time under the selection pressure of systemic treatment. Today, treatment decisions in early breast cancer are based on primary tumour characteristics without considering the disease evolution. Chemoresistant micrometastatic disease is poorly characterised and thus it is not used in current clinical practice as a tool to personalise treatment approaches.

Breast Cancer Subtypes in Patients Aged 70 Years and Older.

Recurrence and survival pattern in breast cancer (bc) patients (pts) ≥ 70 years subcategorized according to subtype and age are still an area of uncertainty. Tumor characteristics, patient demographics, therapies applied, and recurrence pattern were compared between luminal A (LA), luminal B (LB), Her2/neu overexpressing (Her+) and triple-negative (TN) bc subtypes and the age subcategories 70-74, 75-79, ≥80 years. Based on univariate Cox-regression-analyses distant-disease-free-survival (DDFS) differed significantly for bc subtypes (p = 0.

Immune-mediated liver injury of the cancer therapeutic antibody catumaxomab targeting EpCAM, CD3 and Fcγ receptors.

The immunotherapeutic catumaxomab targets EpCAM positive cancers and is approved for the treatment of peritoneal carcinomatosis. To assess the safety of intravenous applications a phase 1 clinical trial was initiated. Treatment of EpCAM positive tumor patients with catumaxomab caused dose dependent hepatitis as evidenced by significant elevations in serum alanine- and aspartate aminotransferases, bilirubin, γGT and induction of the acute phase C-reactive protein (CRP) and the cytokines IL6 and IL8.

Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial.

We investigated rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (n=662) or follicular lymphoma grade 3b (n=21) in first complete remission. Patients were randomized to rituximab maintenance (n=338) or observation (n=345). At a median follow-up of 45 months, the event-free survival rate (the primary endpoint) at 3 years was 80.

The changing world of drug development.

Cancer drug development is undergoing a substantial shift nowadays. The underlying drivers are multi-factorial. On the one side, drug development is performed more rationally than ever, profiting from the scientific advances in molecular biology in general and the elucidation of the various "omes" from genome to metabolome in particular.

A phase I trial of intravenous catumaxomab: a bispecific monoclonal antibody targeting EpCAM and the T cell coreceptor CD3.

Purpose: The aim of the study was to evaluate the safety and determine the maximum tolerated dose (MTD) of intravenous catumaxomab, a trifunctional bispecific antibody that binds to EpCAM on epithelial cancer cells and CD3 on T cells.

Methods: The trial was a dose-escalation study with a 3 + 3 design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab.

A simple method for comparing enzymatic capecitabine activation in various mono- and combination chemotherapies.

Before being able to develop a pharmacodynamic effect, a number of drugs have to be activated by enzymes, which are known to be potentially influenced by manifold factors, leading to a possible alteration of their activity behaviour. Based on capecitabine, we report a simple and rapid method for the estimation and comparison of the so-called 'apparent enzyme activity' (R), not only intra- (different dose levels) but also inter-schedule, to contribute to therapeutic success. Dividing the area under the curve (AUC) of the product by the AUC of the precursor generates a factor which indicates the apparent activity of the enzyme involved in the biotransformation of a compound.

Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial.

Background: Trastuzumab, one important treatment option for HER2-positive metastatic breast cancer (MBC) is limited by its cardiotoxic potential. Lapatinib and pegylated liposomal doxorubicin (PLD) represent a cardiosparing alternative that can cross the blood brain barrier. This is important, because one third of breast cancer patients develop brain metastases.

A phase 1 dose escalation study of BI 831266, an inhibitor of Aurora kinase B, in patients with advanced solid tumors.

Purpose BI 831266 is a potent, selective, low-molecular-weight inhibitor of Aurora kinase B. This trial aimed to determine the maximum tolerated dose (MTD) of BI 831266 in patients with advanced solid tumors (NCT00756223; EudraCT 2008-001631-36; 1257.1).

Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma.

Background: Second-line treatment options for patients with advanced urothelial carcinoma (UC) are limited. Fibroblast growth factor receptor 3 (FGFR3) is dysregulated in UC by activating mutations or protein overexpression in non-mutant tumours. In this study, the efficacy, pharmacodynamics and safety of dovitinib-a broad-targeted inhibitor of tyrosine kinases, including FGFR3-were evaluated in patients with previously treated advanced UC with and without FGFR3 mutations.

Quantitative profiling of peptides from RNAs classified as noncoding.

Only a small fraction of the mammalian genome codes for messenger RNAs destined to be translated into proteins, and it is generally assumed that a large portion of transcribed sequences--including introns and several classes of noncoding RNAs (ncRNAs)--do not give rise to peptide products. A systematic examination of translation and physiological regulation of ncRNAs has not been conducted. Here we use computational methods to identify the products of non-canonical translation in mouse neurons by analysing unannotated transcripts in combination with proteomic data.

Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab.

Background: The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF.

Case Report: The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented.

Impact of co-administered drugs on drug monitoring of capecitabine in patients with advanced colorectal cancer.

Background: Drug monitoring is a useful tool for obtaining detailed information about the disposition of a drug in an individual patient during chemotherapy. According to the international guidelines, the analytical assay for quantification of a compound in biological samples must be validated. Among a number of parameters, peak purity is an important requirement.

A randomised phase II study of pemetrexed versus pemetrexed+erlotinib as second-line treatment for locally advanced or metastatic non-squamous non-small cell lung cancer.

Introduction: Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed+erlotinib in patients with advanced non-squamous NSCLC.

Methods: NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, ≥ 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤ 2 were eligible.