Hartmut Link

• MD, PhD, Professor of Medicine
• Head at Hematology Oncology, Kaiserslautern

Die supportive Therapie ist essenziell für den Erfolg der onkologischen Behandlung. Evidenzbasierte Leitlinien (LL) empfehlen die besten Möglichkeiten der Supportiv-therapie. Onkologische LL sind evidenzbasierte Behandlungsempfehlungen in der medizinischen Versorgung. Wirksame Strategien zur Umsetzung und Einhaltung von LL spielen eine entscheidend...

13 Background: Optimal patient selection for first-line treatment targeting epithelial growth factor receptor (EGFR) in RAS-WT mCRC is based on primary tumor sidedness (PTS) with anti-EGFR being the preferred option for patients with left-sided mCRC (LC). Right-sided mCRCs (RC) are preferentially treated in combination with bevacizumab targeting va...

Purpose Anemia in cancer should be diagnosed and treated according to guideline recommendations. The implementation of ESMO and German guidelines and their effect on anemia correction was analyzed. Methods This retrospective epidemiological study, representative for Germany, analyzed data on anemia management of cancer patients with anemia ≥ grade...

Purpose Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CS...

Introduction: Anemia is a common complication in patients with breast cancer (BC), gastrointestinal tumors (GC), lung cancer (LC), and malignant lymphoma (ML). Guidelines (GL) for the management of anemia (ESMO; DGHO) provide specific algorithms for the diagnosis and treatment of anemia. The aim of this study was to analyze the adherence to GL (GLA...

Infektionen gehören zu den häufigsten Komplikationen bei Tumorpatienten und werden in Fieber unbekannter Ursache („fever of unknown origin“, FUO) sowie klinisch bzw. mikrobiologisch dokumentierte Infektionen eingeteilt. Einer der wichtigsten Risikofaktoren für das Auftreten und einen komplizierten Verlauf von Infektionen ist die Neutropenie. Patien...

Infektionen gehören zu den häufigsten Komplikationen bei Tumorpatienten und werden in Fieber unbekannter Ursache („fever of unknown origin“, FUO) sowie klinisch bzw. mikrobiologisch dokumentierte Infektionen eingeteilt. Einer der wichtigsten Risikofaktoren für das Auftreten und einen komplizierten Verlauf von Infektionen ist die Neutropenie. Patien...

Introduction: Anemia is a frequent complication in patients with breast cancer (BC), gastrointestinal tumors (GC), lung cancer (LC) and malignant lymphomas (ML). Guidelines (GL) on anemia management (ESMO; DGHO) provide dedicated algorithms for diagnosis and treatment of anemia. Aim of the study was to analyze GL adherence (GLAD) in Germany. Method...

PurposeWe assessed the occurrence of neutropenia and febrile neutropenia (FN) and the associated healthcare resource in cancer patients receiving myelosuppressive chemotherapy in combination with pegfilgrastim versus lipegfilgrastim.Methods This is a retrospective analysis using a German health insurance claims database. Adults receiving chemothera...

Background: Anemia is a frequent complication in patients with breast cancer (BC), gastrointestinal tumors (GC), lung cancer (LC) and malignant lymphomas (ML). Guidelines (GL) on anemia management (ESMO, DGHO) provide dedicated algorithms for diagnosis and treatment of anemia. GL adherence (GLAD) was analyzed. Methods: This was a retrospective samp...

Infections in patients with neutropenia following chemotherapy are mostly manifested as fever (febrile neutropenia, FN). Some of the most important determinants of the risk of FN are the type of chemotherapy, the dose intensity and patient-specific factors. When the risk of FN is 20% or more granulopoiesis is prophylactically stimulated with granul...

The frequency and severity of nausea and/or vomiting in patients receiving anticancer drugs are influenced by numerous factors, e.g., by the specific therapeutic agent, the dosage, the schedule and the form of administration. They are also influenced by individual factors of the patients, e.g., young age, female gender, previous cancer treatment, l...

Infections in patients with neutropenia following chemotherapy are mostly manifested as fever (febrile neutropenia, FN). Some of the most important determinants of the risk of FN are the type of chemotherapy, the dose intensity and patient-specific factors. When the risk of FN is 20% or more granulopoiesis is prophylactically stimulated with granul...

Introduction In secondary immunodeficiency, immunoglobulin replacement therapy (IgRT) is recommended by guidelines (GL) for patients with IgG level < 4 g/l and more than 3 infections or a severe infection. IgRT may be appropriate if IgG level < 4 g/l and/or 1–3 less severe infections (≤ grade 2). Methods This was a retrospective sample analysis re...

Anämie und Eisenmangel sind häufige Komplikationen bei Patienten mit soliden Tumoren und hämatologischen Neoplasien, insbesondere wenn sie chemotherapeutisch behandelt werden [1, 10, 16, 17]. Tumortherapie-induzierte Anämie (TIA) ist besonders bei Hb-Werten < 10g/dl mit reduzierter Lebensqualität (QoL) [5, 6, 7] sowie Konsequenzen für ein beeinträc...

Background: Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at...

Introduction: In SID immunoglobulin replacement therapy (IgRT) is recommended by guidelines (GL) for patients (pts) with IgG level < 400mg/dl (or IgG subclass deficiency) and more than 3 infections (INF) or a severe INF (≥ grade 3), and may be appropriate in 1-3 less severe INF (≤ grade 2). GL adherence (GLAD) was analyzed according to Onkopedia GL...

To assess adherence to the current European Society for Medical Oncology (ESMO) clinical practice guideline on bone health in cancer patients and the German guidelines for lung, breast, and prostate cancer among German oncologists in hospitals and office-based physicians and to identify predictors of guideline compliance to assess the needs for ded...

Therapieinduzierte Immundefekte im Zeitalter zielgerichteter Tumortherapien Sekundäre Immundefekte (SID) sind erworbene Funktionsstörungen des Immunsystems, die häufig bei Patienten mit chronischer lymphatischer Leukämie (CLL) oder multiplem Myelom (MM) auftreten. Mit der Erweiterung des Behandlungsspektrums durch zielgerichtete und Immuntherapien...

Purpose Recombinant granulocyte colony-stimulating factors (rG-CSFs), such as filgrastim, are administered to prevent complications in patients receiving chemotherapy. In Europe, a biosimilar to filgrastim, tevagrastim/ratiograstim/biograstim, was approved in 2008. In the USA, the same product was approved as tbo-filgrastim under a 351(a) biologic...

Background Current guidelines (GL) recommend neutropenia prophylaxis with G-CSF after chemotherapy (CTX) for patients with high (≥ 20%), or, if additional risk factors are present, intermediate (≥ 10–20%) risk of febrile neutropenia. The first sample survey in 2012 (NP1) showed lack of GL adherence. The aim of this second sample survey was to evalu...

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Method The process of updating the S3 guideline published in 2012 was based on the adaptation of id...

Purpose The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer. Methods The process of updating the S3 guideline dating from 2012 was based on the adaptation of id...

Objective: To evaluate the clinical and cost benefits of the administration of aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) during highdose chemotherapy (HDCT). Methods: We retrospectively reviewed the charts of patients who received HDCT at our institution between January 2009 and December 2013. Costeffectivene...

Background: The combination of intermediate-dose cytarabine plus mitoxantrone (IMA) can induce high complete remission rates with acceptable toxicity in elderly patients with acute myeloid leukemia (AML). We present the final results of a randomized-controlled trial comparing IMA with the standard 7 + 3 induction regimen consisting of continuous i...

Die Supportivtherapie ist essentieller Bestandteil der onkologischen Therapie und muss insbesondere bei Patienten mit Komorbidität und älteren Patienten gleichermaßen gewertet und beachtet werden. Die Toxizität der Therapieverfahren ist höher, so dass die supportive Therapie früher und intensiver erfolgt als bei den sonstigen Patienten, bei denen a...

PurposeChemotherapy-induced febrile neutropenia (FN) causes treatment delays and interruptions and can have fatal consequences. Current guidelines provide recommendations on granulocyte colony-stimulating factors (G-CSF) for prevention of FN, but guidance is unclear regarding use of short- vs long-acting G-CSF (e.g., filgrastim vs pegfilgrastim/lip...

Fever may be the only clinical symptom at the onset of infection in neutropenic cancer patients undergoing myelosuppressive chemotherapy. A prompt and evidence-based diagnostic and therapeutic approach is mandatory. A systematic search of current literature was conducted, including only full papers and excluding allogeneic hematopoietic stem cell t...

Chronic myeloid leukemia (CML)-study IV was designed to explore whether treatment with imatinib (IM) at 400 mg/day (n=400) could be optimized by doubling the dose (n=420), adding IFN (n=430) or cytarabine (n=158) or using IM after IFN-failure (n=128). From July 2002 to March 2012, 1551 newly diagnosed patients in chronic phase were randomized into...

Background: For the treatment of patients with cancer to be successful and well-tolerated, the complications and side effects of the disease and its treatment must be treated and limited as far as possible. Summarized recommendations based on the constantly increasing evidence in the area of supportive care must be defined, standardized, and commu...

Hintergrund und Ziele: Cisplatin-induzierte Nephrotoxizität betrifft vorrangig die proximalen Tubuli; die tubuläre Schädigung beeinträchtigt wiederum die glomeruläre Filtrationsrate. Niedrigerer Blutdruck führt zur Hypoperfusion der Niere, was eine ischämische akute Nierenschädigung (ANS) begünstigt. In diesem Beitrag untersuchen wir den Zusammenha...

Purpose: The initial results of the APL0406 trial showed that the combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series...

In the context of discussions on the reproducibility of clinical studies, we reanalyzed a prospective randomized study on the role of splenic irradiation as adjunct to the conditioning for hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML). Between 1986 and 1989, a total of 229 patients with CML were randomized; of th...

The aim of this prospective cohort study was to assess current antianemic treatment of cancer patients in German routine practice, including diagnostics, treatments, and quality of life (QoL). 88 study sites recruited 1018 patients at the start of antianemic treatment with hemoglobin (Hb) levels <11 g/dL (females) or <12 g/dL (males). Patients were...

Background: Preclinical data and results from non-randomised trials suggest that the multikinase inhibitor sorafenib might be an effective drug for the treatment of acute myeloid leukaemia. We investigated the efficacy and tolerability of sorafenib versus placebo in addition to standard chemotherapy in patients with acute myeloid leukaemia aged 60...

DNA methylation changes are a constant feature of Acute Myeloid Leukemia. Hypomethylating drugs such as azacitidine are active in AML as monotherapy. Azacitidine monotherapy is not curative. The AML-AZA trial tested the hypothesis that DNA methyltransferase inhibitors such as azacitidine can improve chemotherapy outcome in AML. This randomized, con...

Introduction: Antiemetic guidelines (GL) of ASCO and MASCC/ESMO recommend for highly emetogenic chemotherapy (HEC, emetic risk > 90%) a prophylaxis with a 5-HT3-receptor antagonist (5HT3RA), NK1-receptor antagonist (NK1RA) and dexamethasone (DEX) in the acute phase (first 24h). In the delayed phase DEX should be combined with NK1RA for 2 days (if n...

Iron deficiency and iron deficiency-associated anemia are common complications in cancer patients. Most iron deficient cancer patients present with functional iron deficiency (FID), a status with adequate storage iron, but insufficient iron supply for erythroblasts and other iron dependent tissues. FID is the consequence of the cancer-associated cy...

Febrile neutropenia (FN) after chemotherapy increases complications, morbidity, risk of death, reduction of dose delivery and impairs quality of life. Primary granulocyte-colony stimulating factor (G-CSF) prophylaxis after chemotherapy is recommended in the guideline (GL) if the risk of FN is high (≥20 %) or intermediate (≥10-20 %) with additional...

The cytotoxic therapy of malignant diseases can cause myelosuppression. Neutropenia, febrile neutropenia, and neutropenia-related infections are dose-limiting events during chemotherapy of malignant diseases. The risk of febrile neutropenia and infection is directly related to the degree and duration of neutropenia. Apart from more frequent days in...

Salvage therapy followed by high-dose therapy (HDT) remains a mainstay for patients with relapsed lymphoma, however no optimal regimen has been defined. Here we report on the results of R-DexaBEAM (rituximab, dexamethasone, carmustine, etoposide, cytarabine, melphalan) followed by HDT. Patients aged 18–65 years, Eastern Cooperative Oncology Group p...

Hintergrund Knochenmetastasen kommen häufig beim fortgeschrittenen Mamma- und Prostatakarzinomen vor, Osteolysen sind wiederum typisch beim multiplen Myelom. Knochenerkrankungen durch Metastasen sind bedeutende Ursachen der Morbidität bei Krebs. Tumorzellen können sich in den Nischen der hämatopoetischen Stammzellen absiedeln und dort lange Zeit r...

Background: Cetuximab and bevacizumab have both been shown to improve outcomes in patients with metastatic colorectal cancer when added to chemotherapy regimens; however, their comparative effectiveness when partnered with first-line fluorouracil, folinic acid, and irinotecan (FOLFIRI) is unknown. We aimed to compare these agents in patients with...

The impact of imatinib dose on response rates and survival in older patients with chronic myeloid leukemia in chronic phase has not been studied well. We analyzed data from the German CML-Study IV, a randomized five-arm treatment optimization study in newly diagnosed BCR-ABL-positive chronic myeloid leukemia in chronic phase. Patients randomized to...

OriginalpublikationBennett CL, Djulbegovic B, Norris LB, Armitage JO (2013) Colony-stimulating factors for febrile neutropenia during cancer therapy. N Engl J Med 368:1131–1139HintergrundDie meisten Chemotherapien mit Standarddosierung gehen mit einer 6- bis 8-tägigen Neutropenie einher. Wichtigster Hinweis auf eine Infektion bei neutropenischen Pa...

Hintergrund: Angestrebt wurde eine aktuelle Bestandsaufnahme der Prävalenz und der Behandlung der krebsassoziierten Anämie gemäß den Kriterien der Weltgesundheitsorganisation (WHO) sowie ihrer Risikofaktoren. Patienten und Methoden: Dies war eine prospektive, internetbasierte, 2-tägige Querschnittserhebung zu Patienten mit nichtmyeloider maligner E...

The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new...

Background All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity. Methods We conducted a phase 3, multicenter trial compari...

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medi...

This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medi...

How oncologists adhere to evidence-based G-CSF-guidelines to prevent febrile neutropenia: A sample survey in hospitals and practices in Germany

Background: The aim was to re-evaluate the current prevalence and management of cancer-associated anaemia as defined by the World Health Organisation (WHO) and related risk factors. Patients and methods: This was a prospective, 2-day web-based cross-sectional survey in cancer patients with non-myeloid malignancies in German outpatient clinics....

The role of allogeneic stem cell transplantation (HSCT) as compared to chemotherapy in acute myeloid leukaemia (AML) patients with abnormalities of chromosome 17p [abnl(17p)] has not yet been defined. Therefore, we analysed 3530 AML patients treated in three randomized, prospective, controlled clinical trials and compared post-remission therapies u...

Das Informationsmedium Internet ist aufgrund der weltweiten Präsenz sowie der technischen Fortentwicklung im privaten wie auch beruflichen Bereich aus unserer Gesellschaft nicht mehr wegzudenken. Aufgrund der Vielzahl der onkologischen Informationsportale im Internet mit unterschiedlichen Schwerpunkten ist eine schnelle, zielgerichtete Informations...

Fluorouracil-based chemoradiotherapy is regarded as a standard perioperative treatment in locally advanced rectal cancer. We investigated the efficacy and safety of substituting fluorouracil with the oral prodrug capecitabine. This randomised, open-label, multicentre, non-inferiority, phase 3 trial began in March, 2002, as an adjuvant trial compari...

Fever during neutropenia may be a symptom of severe life threatening infection, which must be treated immediately with antibiotics. If signs of infection persist, therapy must be modified. Diagnostic measures should not delay treatment. If the risk of febrile neutropenia after chemotherapy is ≥ 20%, then prophylactic therapy with G-CSF is standard...

This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). P...

4014 Background: 5-FU based CRT is regarded standard perioperative treatment in LARC. Here we report safety data of a non-inferiority phase III trial investigating (neo-)adjuvant CRT with Cape in comparison with 5-FU. Methods: Patients (pts) aged ≥18 years with LARC UICC stages II or III were recruited in this two-arm, two-strata randomized phase-I...

8029 Background: Superiority of irinotecan over etoposide in combination with cis- or carboplatin was demonstrated in a Japanese and a Scandinavian phase III trial. However, both cisplatin-based North American phase III studies could not detect any difference in efficacy. We report the final results of the German randomized phase III trial comparin...

Carcinomas of unknown primary (CUP) account for approximately 2-5% of all cancer diagnoses. Except for some subsets with favorable prognosis, for most of these patients treatment options are limited, and no standard first-line regimen has been identified. We performed a phase II study with oxaliplatin (OX) and capecitabine (CAP) as first-line treat...

Anaemia occurs in 50% of tumour patients which should be clarified by differential diagnosis and treated in accordance with the underlying causes. The quality of life of anaemic tumour patients can be improved by correction of the anaemia. Anaemia is often caused by activation of the immune system in chronic diseases (ACD anaemia of chronic disease...

Platinum/taxane combinations are widely used in patients with carcinoma of unknown primary (CUP), yielding response rates of 30% and median overall survival of 9-11 months in selected patients. Yet these combinations have not been subject to a randomised trial to overcome selection bias, a major problem in CUP. We randomised 92 patients to either p...

The study aimed to demonstrate the noninferiority of capecitabine to 5-fluorouracil (5-FU)/folinic acid (FA), in relation to progression-free survival (PFS) after first-line treatment of metastatic colorectal cancer and the benefit of adding celecoxib (C) to irinotecan/fluoropyrimidine regimens compared with placebo (P). Patients were randomly assi...

Anemia is frequently experienced by cancer patients receiving chemotherapy and can negatively impact the patient's prognosis. Blood transfusions, iron supplementation (in absolute or functionally iron-deficient anemias), and erythropoiesis-stimulating agents (ESAs) are among the treatment options for anemia. Treatment options for anemia management...

The prognosis of neoplastic meningitis is poor even with therapy. The diagnosis of neoplastic meningitis mostly indicates a disseminated metastasis of the cancer disease. The present gold standard for the diagnosis of neoplastic meningitis is nuclear magnetic resonance of the central nervous system and the spinal column. Disseminated tumor cells in...

Anaemia is frequently diagnosed in patients with cancer, and may have a detrimental effect on quality of life (QoL). We previously conducted a systematic literature review (1996–2003) to produce evidence-based guidelines on the use of erythropoietic proteins in anaemic patients with cancer.[Bokemeyer C, Aapro MS, Courdi A, et al. EORTC guidelines f...

The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics alone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy. A prospective, randomized controlled trial was conducted at 22 cancer centers in Germany. Patients w...