Heike Richly's research while affiliated with University of Duisburg-Essen and other places

Publications (75)

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Purpose In uveal melanoma patients, liver metastases can be treated by hepatic artery infusion chemotherapy (HAIC). During this procedure, melphalan or, less frequently, fotemustine is infused into the hepatic artery or the hepatic lobe arteries in regularly repeated interventions to achieve local tumor control. The aim of this study was to investi...
Article
Background Growth and differentiation factor 15 (GDF-15) is a TGF-β superfamily member physiologically expressed mainly in placenta and linked to feto-maternal tolerance. Under pathophysiologic conditions, prevention of excessive immune cell infiltration during tissue damage and cachexia induction have been ascribed to GDF-15. Recent research has t...
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Background: Eye salvaging therapy of malignant melanomas of the uvea can preserve the eye in most cases, but still about half of patients die from metastatic disease. Previous analyses of cell-free DNA from plasma had shown detectable levels of tumor-specific GNAQ/GNA11 mutations in patients with the clinical diagnosis of progressive disease. Howe...
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Background The aim of the study was to evaluate pretreatment inflammatory markers as prognostic factors in patients with unresectable uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion. Patients and methods 54 patients (44% male, median age: 61 years) were retrospectively assessed. A median of 3 (range: 1–11) treatme...
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Purpose To assess serum lactate dehydrogenase (LDH) as a pretreatment prognostic factor in patients with uveal melanoma liver metastases treated with transarterial hepatic chemoperfusion (THC). Materials and Methods 56 patients (48 % male, median age: 63.5 years) underwent a median of 4 THC sessions. Kaplan-Meier for median overall survival (OS) an...
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PurposeDiagnosis and treatment of breast cancer have changed profoundly over the past 25 years. The outcome improved dramatically and was well quantified for early stage breast cancer (EBC). However, progress in the treatment of metastatic disease has been less convincingly demonstrated. We have studied survival data of patients with metastatic bre...
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Background: The clinical activity of fibroblast growth factor receptor (FGFR) inhibitors seems restricted to cancers harbouring rare FGFR genetic aberrations. In preclinical studies, high tumour FGFR mRNA expression predicted response to rogaratinib, an oral pan-FGFR inhibitor. We aimed to assess the safety, maximum tolerated dose, recommended pha...
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Introduction: IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods:...
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494 Background: Activation of FGFR signaling is involved in a variety of malignancies including advanced urothelial cancer (UC). Rogaratinib is an oral pan-FGFR kinase inhibitor. We report here the results from a phase I expansion cohort in UC patients prescreened for FGFR1-3 mRNA expression levels and activating mutations. (NCT01976741) Methods: P...
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9511 Background: There is no established systemic treatment for pts with MUM. The STREAM study evaluated the efficacy of the oral multikinase inhibitor S in chemonaïve pts with MUM with the primary endpoint progression-free survival (PFS). Methods: During the initial 56d run-in period all pts received oral S 400 mg bid with concomitant monitoring b...
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Purpose This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the Aurora B kinase inhibitor BI 811283 in patients with advanced solid tumors. Methods BI 811283 was administered via 24-h infusion on Days 1 and 15 of a 4-week cycle (schedule A) or Day 1 of a 3-week cycl...
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To the editor: The anaplastic lymphoma kinase (ALK) gene is expressed in >50% of anaplastic large-cell lymphomas (ALCLs).[1][1] Although most patients with ALK-positive ALCL respond well to anthracycline-based chemotherapy, relapses do occur (5-year failure-free survival 60%) and require salvage
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Overall survival (OS) of patients with hepatic metastases of uveal melanoma is strongly linked with hepatic tumor control. Due to the lack of an effective systemic chemotherapy, locoregional therapies like radioembolization should play an increasingly important role. To report complications and response rates of radioembolization as salvage therapy...
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To report the nonrandomized first-in-human phase I trial of PRS-050, a novel, rationally engineered Anticalin based on human tear lipocalin that targets and antagonizes vascular endothelial growth factor A (VEGF-A). Patients with advanced solid tumors received PRS-050 at 0.1 mg/kg to 10 mg/kg by IV in successive dosing cohorts according to the 3+3...
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Biomarker-stratified cancer pharmacotherapy was pioneered in the care of breast cancer patients. The utility of agents modulating hormone receptors, synthesis of steroid hormones, or HER2-targeting agents has been greatly enhanced by the detection of predictive biomarkers in diagnostic tumor samples. Based on deeper understanding of breast cancer b...
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Tivozanib is a potent selective tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. This Phase Ib study investigated the safety/tolerability, pharmacokinetics (PK), and activity of tivozanib with weekly paclitaxel in metastatic breast cancer (MBC). MBC patients with no prior VEGFR TKI treatment rece...
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Multiple investigational drugs are currently explored in cancer patient populations defined by specific biomarkers. This demands a new process of patient selection for clinical trials. Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or co...
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4035 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumours, but PDAC is still associated with a poor prognosis in advanced disease with an overall 5-year survival of only about 15%. Therefore there is a need for new treatment strategies. To improve the standard therapy with gemcitabine we initiated a prospe...
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Purpose Pazopanib plus gemcitabine combination therapy was explored in patients with advanced solid tumors. Methods In a modified 3 + 3 enrollment scheme, oral once-daily pazopanib was administered with intravenous gemcitabine (Days 1 and 8, 21-day cycles). Three protocol-specified dose levels were tested: pazopanib 400 mg plus gemcitabine 1,000 m...
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2086 Background: Deregulation of the PI3K/AKT pathway has been preclinically involved in the pathophysiology of GBM. The mammalian target of rapamycin (mTOR) is an important downstream mediator of PI3K/AKT signalling. The mTOR-inhibitor temsirolimus (Tem) achieves significant drug levels in brain. Thus, Tem may be effectively combined with irinotec...
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In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). Patients received oral regorafenib 60-220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Asse...
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Background: Anticalins are a new class of therapeutic small protein (20kDa) antibody mimetics based on human lipocalins which can be engineered to bind key molecules involved in tumor progression with high affinity and specificity. PRS-050 (40kDa PEGylated Anticalin) targets VEGF-A. The first clinical trial of this putative therapeutic drug is repo...
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s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 12-16, 2011; San Francisco, CA Background: There is no effective systemic therapy for patients (pts) with metastatic uveal melanoma (metUvMel). Due to the paucity of clinical trials pts are frequently offered individual treatment options. We have analyzed th...
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Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Introduction: TriN 2755 is a cytotoxic compound with a novel chemical structure, which carries a triazene group as cytotoxic principle. TriN 2755 demonstrated antitumor activity in human colon carcinoma, breast cancer and malignant melanoma models in nude mouse and rat. In co...
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1092 Background: Tivozanib (T; AV-951) is a potent and selective oral small molecule tyrosine kinase inhibitor (TKI) of VEGFR-1, -2, and -3. This phase Ib open-label, multicenter study investigated the safety/tolerability, pharmacokinetics (PK), and activity of T in combination with weekly paclitaxel (P) in metastatic breast cancer (MBC). Methods:...
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Background Tivozanib (T, AV-951) is a potent and selective oral small molecule tyrosine kinase inhibitor (TKI) of VEGFR-1, -2, and -3; its high specificity for the receptor may afford improved activity over multi-targeted TKIs. This phase 1b open-label, multicenter study investigated the safety and tolerability, pharmacokinetics (PK), activity, and...
Conference Paper
Background: MGN1703 is a novel synthetic DNA-based immunomodulator, which acts as a toll-like receptor 9 agonist. The safety of MGN1703 has previously been shown in several animal toxicity studies models as well as in the first clinical observations of MGN1703 in form of Investigator-initiated-trials (ITT). A clinical phase I study was conducted in...
Conference Paper
Background: MGN1703 is a novel synthetic DNA-based immunomodulator, which acts as a toll-like receptor 9 agonist. The antineoplastic activity of MGN1703 has been previously shown in vitro and in several animal models. In this clinical phase I study patients with metastatic cancer without further treatment options were treated with MGN1703. Method:...
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e13065 Background: BI 811283 has demonstrated potent antitumor activity in cancer models at well-tolerated doses, with hallmarks of Aurora B inhibition. Methods: Patients with advanced, nonresectable and/or metastatic solid tumors were randomized to two treatment schedules (4-week and 3-week) in a bicentric phase I dose-escalation study. The primar...
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3011 Background: The serine/threonine kinase Aurora B regulates several mitotic processes and is an attractive target for therapeutic intervention. BI 811283 has demonstrated potent antitumor activity in cancer models at well-tolerated doses, with hallmarks of Aurora B inhibition. Methods: Patients with advanced, nonresectable and/or metastatic sol...
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4730 Background The DNA-based immunomodulator MGN1703 stimulates the innate and cellular immune system mainly via the TLR9-receptor. The results of the recent in vivo experiments showed potent anti-tumor efficacy of MGN1703 in several mouse tumor models in prophylactic and therapeutic settings as well as a good safety profile in various animals. T...
Conference Paper
Background: The DNA-based immunomodulator MGN1703 stimulates the innate and cellular immune system mainly via the TLR9-receptor. The results of the recent in vivo experiments showed potent anti-tumor efficacy of MGN1703 in several mouse tumor models in prophylactic and therapeutic settings as well as a good safety profile in various animals. Two in...
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Sorafenib, an oral multikinase inhibitor, shows efficacy in renal cell and hepatocellular carcinoma (HCC) and is well tolerated when combined with doxorubicin in other solid tumours. Eighteen patients with inoperable HCC received doxorubicin 60 mg/m(2) IV for up to six 3-week cycles. Sorafenib 400mg bid was administered continuously starting day 4....
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Sorafenib is an oral multikinase inhibitor that inhibits Raf serine/threonine kinases and receptor tyrosine kinases involved in tumor growth and angiogenesis. It has demonstrated preclinical and clinical activity in several tumor types. Sorafenib 400 mg twice daily (bid) has been approved in several countries worldwide for the treatment of renal ce...
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Sorafenib (BAY 43-9006), a novel, oral multi-kinase inhibitor, blocks serine/threonine and receptor tyrosine kinases in the tumor and vasculature. Sorafenib demonstrated single-agent activity in Phase I studies, and was tolerated and inhibited tumor growth in combination with doxorubicin in preclinical studies. This Phase I dose-escalation study de...
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Sorafenib (BAY 43-9006), a multiple kinase inhibitor, has been shown to inhibit tumor growth and tumor angiogenesis by targeting Raf kinase, vascular endothelial growth factor receptor, and platelet-derived growth factor receptor. In phase I studies, sorafenib demonstrated single-agent activity in patients with advanced solid tumors and was success...
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BAY 43-9006 is a novel dual-action Raf kinase and vascular endothelial growth factor receptor inhibitor that inhibits tumor cell proliferation and angiogenesis. This study established the safety and pharmacokinetics of BAY 43-9006 in 69 patients with advanced refractory solid tumors. BAY 43-9006 (50 to 800 mg) was administered once or twice daily o...
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BBR 3576 is a novel aza-anthrapyrazole with limited potential for cardiotoxicity in preclinical models. This phase I clinical and pharmacokinetic study was performed to determine the maximum tolerated dose, the dose-limiting toxicity (DLT) and the pharmacokinetic profile of BBR 3576 administered i.v. as a 1-h infusion repeated every 4 weeks. In tot...