Defining the role of surgery for patients with multiple brain metastases.

PURPOSE: To better define the role of surgery, we investigated survival and functional outcomes in patients with multiple brain metastases. METHODS: Pertinent clinical and radiological data of 131 consecutive patients (156 surgeries) were analyzed retrospectively. RESULTS: Surgical indications included mass effect (84.6%) and need for tissue acquisition (44.9%, for molecularly informed treatment: 10 patients). Major (i.e. CTCAE grade 3-5) neurological, surgical and medical complication were observed in 6 (3.8%), 12 (7.7%), and 12 (7.7%) surgical cases. Median preoperative and discharge KPS were 80% (IQF: 60-90%). Median overall survival (mOS) was 7.4 months. However, estimated 1 and 2 year overall survival rates were 35.6% and 25.1%, respectively. Survival was dismal (i.e. mOS ≤ 2.5 months) in patients who had no postoperative radio- and systemic therapy, or who incurred major complications. Multivariate analysis with all parameters significantly correlated with survival as univariate parameters revealed female sex, oligometastases, no major new/worsened neurological deficits, and postoperative radio- and systemic therapy as independent positive prognostic parameters. Univariate positive prognostic parameters also included histology (best survival in breast cancer patients) and less than median (0.28 cm3) residual tumor load. CONCLUSIONS: Surgery is a reasonable therapeutic option in many patients with multiple brain metastases. Operations should primarily aim at reducing mass effect thereby preserving the patients' functional health status which will allow for further local (radiation) and systemic therapy. Surgery for the acquisition of metastatic tissue (more recently for molecularly informed treatment) is another important surgical indication. Cytoreductive surgery may also carry a survival benefit by itself.

[Cancer in people with an intellectual disability in Germany: prevalence, genetics, and care situation]. / Krebserkrankungen bei Menschen mit einer Intelligenzminderung in Deutschland: Prävalenzen, Genetik und Versorgungslage.

Intellectual disability has a prevalence rate of approximately 1% of the population; in Germany, this is around 0.5-1 million people. The life expectancy of this group of people is reduced, with cancer being one of the most common causes of death (approx. 20%). Overall, the risk of cancer and mortality is increased compared to the general population.Certain genetic syndromes predispose to cancer in this vulnerable group, but associated comorbidities or lifestyle could also be risk factors for cancer. People with cognitive impairments are less likely to attend preventive check-ups, and challenges arise in medical care due to physical, communicative, and interactional characteristics. Optimized cooperation between clinical centers for people with disabilities and the respective cancer centers is required in order to tailor the processes to the individual.In Germany, there is a lack of data on the prevalence of cancer entities and the use and need for healthcare services. There is an urgent need to focus attention on cancer prevention, treatment, and research in the vulnerable and heterogeneous group of people with intellectual disabilities suffering from cancer in order to effectively counteract the increase in cancer-related deaths in this population group.The article summarizes specialist knowledge on cancer in people with an intellectual disability, identifies special features of treatment, presents care structures, and derives specific requirements for clinics and research.

Durable response from fibroblast growth factor receptor inhibition in intrahepatic cholangiocarcinoma terminated by metachronous acute myeloid leukemia: a case report.

INTRODUCTION: Advances in the treatment of biliary tract cancer have been made possible through gains in genomic and epigenetic tumor understanding. The use of fibroblast growth factor receptor inhibitor has enabled significant clinical improvement in a specific group of patients with intrahepatic cholangiocarcinoma, some of whom with very durable responses. CASE PRESENTATION: We present the case of a 69-year-old Caucasian patient with advanced intrahepatic cholangiocarcinoma who received the therapy with selective oral inhibitor of fibroblast growth factor receptor 1, 2, and 3 pemigatinib after multiple previous chemotherapies. This resulted in a durable stable disease condition for 15 months with good tolerability. The diagnosis of acute myeloid leukemia was an unanticipated serious adverse event, in which the impact of fibroblast growth factor receptor inhibition could not yet be determined due to inadequate data. CONCLUSIONS: It is still possible to achieve durable tumor response in advanced previously treated intrahepatic cholangiocarcinoma through targeted therapies. The prolonged progression free survival means that there could be an increased risk of secondary malignancy in this patient group, which necessitates diagnostic and therapeutic strategies.

AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants.

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients. However, ongoing epidemiological changes and rise of new virus variants require repeated revisions and adaptations of prophylaxis and treatment strategies to meet these new challenges. Therefore, this guideline provides an update on evidence-based recommendations with regard to vaccination, pharmacological prophylaxis and treatment of COVID-19 in cancer patients in light of the currently dominant omicron variants. It was developed by an expert panel of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) based on a critical review of the most recent available data.

Targeting NF-κB Signaling in Cancer Stem Cells: A Narrative Review.

Among the cell populations existing within a tumor, cancer stem cells are responsible for metastasis formation and chemotherapeutic resistance. In the present review, we focus on the transcription factor NF-κB, which is present in every cell type including cancer stem cells. NF-κB is involved in pro-tumor inflammation by its target gene interleukin 1 (IL1) and can be activated by a feed-forward loop in an IL1-dependent manner. Here, we summarize current strategies targeting NF-κB by chemicals and biologicals within an integrated cancer therapy. Specifically, we start with a tyrosine kinase inhibitor targeting epidermal growth factor (EGF)-receptor-mediated phosphorylation. Furthermore, we summarize current strategies of multiple myeloma treatment involving lenalidomide, bortezomib, and dexamethasone as potential NF-κB inhibitors. Finally, we discuss programmed death-ligand 1 (PD-L1) as an NF-κB target gene and its role in checkpoint therapy. We conclude, that NF-κB inhibition by specific inhibitors of IκB kinase was of no clinical use but inhibition of upstream and downstream targets with drugs or biologicals might be a fruitful way to treat cancer stem cells.

Surgical Treatment of Cerebellar Metastases: Survival Benefits, Complications and Timing Issues.

We retrospectively studied 73 consecutive patients who underwent surgery 2015-2020 for removal of cerebellar metastases (CM). Median overall survival (medOS) varied widely between patients and compared favorably with the more recent literature (9.2, 25-75% IQR: 3.2-21.7 months vs. 5-8 months). Prognostic factors included clinical (but not radiological) hydrocephalus (medOS 11.3 vs. 5.2 months, p = 0.0374). Of note, a third of the patients with a KPI <70% or multiple metastases survived >12 months. Chemotherapy played a prominent prognostic role (medOS 15.5 vs. 2.3, p < 0.0001) possibly reflecting advances in treating systemic vis-à-vis controlled CNS disease. Major neurological (≥30 days), surgical and medical complications (CTCAE III-V) were observed in 8.2%, 13.7%, and 9.6%, respectively. The occurrence of a major complication markedly reduced survival (10.7 vs. 2.5 months, p = 0.020). The presence of extracerebral metastases did not significantly influence OS. Postponing staging was not associated with more complications or shorter survival. Together these data argue for individualized decision making which includes offering surgery in selected cases with a presumably adverse prognosis and also occasional urgent operations in cases without a preoperative oncological work-up. Complication avoidance is of utmost importance.

Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematologic malignancies and solid tumors: 2020 updated guidelines of the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology (AGIHO/DGHO).

Hematologic and oncologic patients with chemo- or immunotherapy-related immunosuppression are at substantial risk for bacterial infections and Pneumocystis jirovecii pneumonia (PcP). As bacterial resistances are increasing worldwide and new research reshapes our understanding of the interactions between the human host and bacterial commensals, administration of antibacterial prophylaxis has become a matter of discussion. This guideline constitutes an update of the 2013 published guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO). It gives an overview about current strategies for antibacterial prophylaxis in cancer patients while taking into account the impact of antibacterial prophylaxis on the human microbiome and resistance development. Current literature published from January 2012 to August 2020 was searched and evidence-based recommendations were developed by an expert panel. All recommendations were discussed and approved in a consensus conference of the AGIHO prior to publication. As a result, we present a comprehensive update and extension of our guideline for antibacterial and PcP prophylaxis in cancer patients.

Prophylaxis, diagnosis and therapy of infections in patients undergoing high-dose chemotherapy and autologous haematopoietic stem cell transplantation. 2020 update of the recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

To ensure the safety of high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT), evidence-based recommendations on infectious complications after HDC/ASCT are given. This guideline not only focuses on patients with haematological malignancies but also addresses the specifics of HDC/ASCT patients with solid tumours or autoimmune disorders. In addition to HBV and HCV, HEV screening is nowadays mandatory prior to ASCT. For patients with HBs antigen and/or anti-HBc antibody positivity, HBV nucleic acid testing is strongly recommended for 6 months after HDC/ASCT or for the duration of a respective maintenance therapy. Prevention of VZV reactivation by vaccination is strongly recommended. Cotrimoxazole for the prevention of Pneumocystis jirovecii is supported. Invasive fungal diseases are less frequent after HDC/ASCT, therefore, primary systemic antifungal prophylaxis is not recommended. Data do not support a benefit of protective room ventilation e.g. HEPA filtration. Thus, AGIHO only supports this technique with marginal strength. Fluoroquinolone prophylaxis is recommended to prevent bacterial infections, although a survival advantage has not been demonstrated.

Central venous catheter-related infections in hematology and oncology: 2020 updated guidelines on diagnosis, management, and prevention by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

[Infections as oncologic emergencies]. / Infektionen als Notfall der Onkologie: Übersicht über die aktuellen Leitlinien.

Background: Patients with oncologic diseases, particularly those with hematologic malignancies, are at an increased risk of common infections and unique treatment-related complications with high mortality and morbidity. The annual incidence and prevalence of cancer in Germany is rising. Although modern treatments have generally led to improved survival, increasing age, comorbidities, and frailty of the patients require multidisciplinary strategies for handling complex therapeutic concepts and treatment of the associated complications. Methods: A selective literature search and guidelines from the European Society for Medical Oncology (ESMO), the German Society of Hematology and Medical Oncology (Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, DGHO), the Infectious Diseases Working Group of the DGHO (Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie, AGIHO), and the American Society of Clinical Oncology (ASCO) formed the basis of this study. Conclusion: Recognition of severe infections in cancer patients and their discrimination from treatment-associated complications is a challenge. Neutropenic fever is the most frequent infectious emergency in oncology. Early empiric treatment with broad-spectrum antibiotics and escalated diagnostic strategies are needed to successfully treat this vulnerable patient group. In this article, a range of potentially life-threatening infections in immunocompromised patients are discussed.

[Infections as oncologic emergencies]. / Infektionen als Notfall der Onkologie: Übersicht über die aktuellen Leitlinien.

BACKGROUND: Patients with oncologic diseases, particularly those with hematologic malignancies, are at an increased risk of common infections and unique treatment-related complications with high mortality and morbidity. The annual incidence and prevalence of cancer in Germany is rising. Although modern treatments have generally led to improved survival, increasing age, comorbidities, and frailty of the patients require multidisciplinary strategies for handling complex therapeutic concepts and treatment of the associated complications. METHODS: A selective literature search and guidelines from the European Society for Medical Oncology (ESMO), the German Society of Hematology and Medical Oncology (Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie, DGHO), the Infectious Diseases Working Group of the DGHO (Arbeitsgemeinschaft Infektionen in der Hämatologie und Onkologie, AGIHO), and the American Society of Clinical Oncology (ASCO) formed the basis of this study. CONCLUSION: Recognition of severe infections in cancer patients and their discrimination from treatment-associated complications is a challenge. Neutropenic fever is the most frequent infectious emergency in oncology. Early empiric treatment with broad-spectrum antibiotics and escalated diagnostic strategies are needed to successfully treat this vulnerable patient group. In this article, a range of potentially life-threatening infections in immunocompromised patients are discussed.

Treatment of invasive fungal diseases in cancer patients-Revised 2019 Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

BACKGROUND: Invasive fungal diseases remain a major cause of morbidity and mortality in cancer patients undergoing intensive cytotoxic therapy. The choice of the most appropriate antifungal treatment (AFT) depends on the fungal species suspected or identified, the patient's risk factors (eg length and depth of granulocytopenia) and the expected side effects. OBJECTIVES: Since the last edition of recommendations for 'Treatment of invasive fungal infections in cancer patients' of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) in 2013, treatment strategies were gradually moving away from solely empirical therapy of presumed or possible invasive fungal diseases (IFDs) towards pre-emptive therapy of probable IFD. METHODS: The guideline was prepared by German clinical experts for infections in cancer patients in a stepwise consensus process. MEDLINE was systematically searched for English-language publications from January 1975 up to September 2019 using the key terms such as 'invasive fungal infection' and/or 'invasive fungal disease' and at least one of the following: antifungal agents, cancer, haematological malignancy, antifungal therapy, neutropenia, granulocytopenia, mycoses, aspergillosis, candidosis and mucormycosis. RESULTS: AFT of IFDs in cancer patients may include not only antifungal agents but also non-pharmacologic treatment. In addition, the armamentarium of antifungals for treatment of IFDs has been broadened (eg licensing of isavuconazole). Additional antifungals are currently under investigation or in clinical trials. CONCLUSIONS: Here, updated recommendations for the treatment of proven or probable IFDs are given. All recommendations including the levels of evidence are summarised in tables to give the reader rapid access to key information.

Effectiveness of eslicarbazepine acetate in dependency of baseline anticonvulsant therapy: Results from a German prospective multicenter clinical practice study.

Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells.

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score.

IMPORTANCE: REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline α-fetoprotein (αFP). OBJECTIVE: To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial. DESIGN, SETTINGS, AND PARTICIPANTS: Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8). INTERVENTIONS: Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks. MAIN OUTCOMES AND MEASURES: Overall survival (OS), defined as time from randomization to death from any cause. RESULTS: In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline αFP levels of 400 ng/mL (to convert ng/mL to µg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P = .01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher incidence of grade 3 or higher treatment-emergent adverse events, including ascites and asthenia, and special-interest events, including liver injury and/or failure and bleeding, compared with patients with Child-Pugh scores of 5 or 6. CONCLUSIONS AND RELEVANCE: In unselected patients, a trend for ramucirumab survival benefit was observed only for patients with a Child-Pugh score of 5. In patients with baseline αFP levels of 400 ng/mL or more, a ramucirumab survival benefit was observed for Child-Pugh scores of 5 and 6. Ramucirumab had a manageable toxic effect profile. These results support the ongoing REACH-2 study of ramucirumab in patients with advanced HCC with underlying Child-Pugh A cirrhosis and baseline αFP levels of 400 ng/mL or more. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01140347.

Sunitinib added to FOLFIRI versus FOLFIRI in patients with chemorefractory advanced adenocarcinoma of the stomach or lower esophagus: a randomized, placebo-controlled phase II AIO trial with serum biomarker program.

BACKGROUND: As a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response. METHODS: This double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively. RESULTS: Overall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70-1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50-1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed. CONCLUSIONS: Although sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted. TRIAL REGISTRATION: This study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland-Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009.

Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer: a randomised phase II trial of the Arbeitsgemeinschaft Internistische Onkologie.

INTRODUCTION: Human epidermal growth factor receptor 2 (HER2) amplification is present in a subgroup of gastroo-esophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-epidermal growth factor receptor (EGFR) and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC. MATERIALS AND METHODS: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250mg per day 1-21 plus capecitabine (CAP) 2000mg/m(2) on days 1-14 of a 21-day cycle or LAP 1500mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary end-point was the objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). We aimed to include 38 pts per arm to show an interesting response rate of ⩾20% in either of the two arms. RESULTS: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% confidence interval (CI): 1.37-34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38-61) days in the LAP group and 83 (95% CI: 42-86) days in the LAP+CAP group. Other secondary efficacy end-points (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhoea were higher with LAP+CAP (61%; 95% CI: 35-83) compared to 26% (95% CI 9-51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] versus 17 [90%]). DISCUSSION: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. (ClinicalTrials.gov Identifier, NCT01145404).

Antimicrobial therapy of febrile complications after high-dose chemotherapy and autologous hematopoietic stem cell transplantation--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

More than 18,000 autolgous transplantation were performed in Europe in the year 2009. It as a routine procedure in experienced centres. Even if there is a low mortality rate, infections are a major issue after transplantation, occurring in more than 60 % of the patients. In this review we discuss all aspects of infections after autologous stem transplantation, including epidemiology, diagnostics, therapeutic algorithms, prophylaxis and supportive therapy.