Capecitabine and bevacizumab with or without vinorelbine in first-line treatment of HER2/neu-negative metastatic or locally advanced breast cancer: final efficacy and safety data of the randomised, open-label superiority phase 3 CARIN trial
Welt A.,University of Duisburg - Essen |
Marschner N.,The Interdisciplinary Center |
Lerchenmueller C.,Oncology Outpatient Center |
Decker T.,Oncology Outpatient Center |
And 5 more authors.
Breast Cancer Research and Treatment | Year: 2016
The study was designed to evaluate efficacy and superiority of capecitabine/bevacizumab + vinorelbine (CAP/BEV/VIN) compared to CAP/BEV alone. Main purpose was to introduce a taxane-/anthracycline-free first-line treatment in advanced breast cancer (ABC), in order to avoid long-term toxicities. In this open-label, superiority, phase 3 trial, patients with HER2-negative ABC were randomized 1:1 to receive either oral CAP at 1000 mg/m2 [twice daily, days 1–14, q3w] plus intravenous BEV at 15 mg/kg [day 1, q3w] (arm A) or in addition to this protocol intravenous VIN at 25 mg/m2 [days 1 + 8, q3w] (arm B) until disease progression, unacceptable toxicity or withdrawal of consent. Between 26 February 2009 and 26 October 2012, we randomised 600 patients (arm A N = 300; arm B N = 300) from 57 German outpatient-centres and 2 university hospitals. Median progression-free survival (PFS) (primary endpoint) was not improved with VIN (CAP/BEV, 8.8 months; CAP/BEV/VIN, 9.6 months; HR 0.84 [95 % CI 0.70–1.01], P = 0.058). Median overall survival (OS) (secondary endpoint) was 25.1 and 27.2 months for CAP/BEV and CAP/BEV/VIN, respectively, average HR 0.85 [95 % CI 0.70–1.03], P = 0.104). The 1- and 2-year OS rates appeared to be similar (78.0 and 77.0 %; 53.0 and 54.0 %). Toxicity profiles were generally mild and manageable. Adverse events occurred more frequently in arm B. Regarding the balance between clinical efficacy (PFS, OS) and toxicity, the CAP/BEV combination provides a favourable treatment option in first-line ABC avoiding taxane- and/or anthracycline-induced long-term toxicity. Superiority of CAP/BEV/VIN was not met, and side effects were even enhanced. Nevertheless, no safety issues occurred. © 2016, The Author(s).
Schimanski C.C.,University Hospital Freiburg |
Mohler M.,University Hospital Freiburg |
Schon M.,Municipal Hospital of Karlsruhe |
van Cutsem E.,University Hospital Gasthuisberg |
And 20 more authors.
BMC Cancer | Year: 2012
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.Methods/Design: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 μg once weekly for 8 weeks, followed by s.c. L-BLP25 930 μg maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion.Trial Registration: EudraCT Number 2011-000218-20. © 2012 Schimanski et al; licensee BioMed Central Ltd.
Goebell P.J.,Friedrich - Alexander - University, Erlangen - Nuremberg |
Muller L.,Oncology Outpatient Center |
Hurtz H.-J.,Group Practice for Oncology |
Koska M.,IOMEDICO |
And 2 more authors.
Clinical Genitourinary Cancer | Year: 2016
Background The management of symptoms associated with treatment of metastatic renal cell carcinoma (mRCC) is crucial to ensure treatment adherence and outcome. The perception of symptoms can vary between the treating physician and patient, leading to assumptions and subsequent changes in treatment, potentially affecting treatment effectiveness. The aim of the present cross-sectional study was to evaluate the perception of the common symptoms of fatigue, mucositis, hand-foot syndrome, and dysgeusia in patients with mRCC receiving systemic therapies in routine practice. Patients and Methods German patients receiving first-line systemic treatment for mRCC and their physicians were independently queried about the incidence and severity of fatigue, mucositis, hand-foot syndrome, and dysgeusia. Patients also completed the Functional Assessment of Cancer Therapy-General questionnaire to assess their quality of life (QOL). The effect of the 4 symptoms on QOL was analyzed using linear regression modeling. Results A total of 63 matching questionnaires were completed by both physicians and patients with first-line treatment. The incidence and severity of symptoms differed between the patients and physicians. Patients rated the severity of symptoms significantly higher than did the physicians. A greater severity of symptoms correlated with a lower QOL. In multivariate regression analysis, fatigue adversely affected overall QOL. Conclusion Physicians underestimated the severity of common symptoms in patients with mRCC. The incorporation of patient-reported outcome measures into routine practice might increase awareness of patients' overall QOL and thereby potentially improve treatment adherence. A thorough evaluation of fatigue, its potential underlying causes, and active measures to manage fatigue could potentially improve patients' QOL. © 2016 Elsevier Inc. All rights reserved.
Steinmetz T.,Outpatient Clinic for Hematology and Oncology |
Schroder J.,Outpatient Clinic for Oncology |
Plath M.,Outpatient Clinic for Oncology |
Link H.,Westpfalz Klinikum |
And 3 more authors.
Anemia | Year: 2016
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 followed up for 12 weeks. 63% of the patients had inoperable solid tumors, 22% operable solid tumors, and 15% hematological malignancies. Over 85% received chemotherapy. Median age was 67 years; 48% were male. Red blood cell transfusions (RBCTx) were given to 59% of all patients and to 55% of the patients with Hb ≥8 g/dL on day 1 of the observation period (day 1 treatment). Erythropoiesis-stimulating agents (ESAs) were the second most frequently applied day 1 treatment (20%), followed by intravenous (IV) iron (15%) and ESA + IV iron (6%). Only about a third of patients were tested for blood serum iron parameters at the start of treatment. Overall, more than half of the patients had long-term responses to antianemic therapy. Our data suggest that in routine practice diagnostics for treatable causes of anemia are underused. A high proportion of cancer patients receive RBCTx. It should be discussed whether thorough diagnostics and earlier intervention could decrease the need for RBCTx. This trial is registered with NCT01795690. © 2016 Tilman Steinmetz et al.
Knauf W.,Onkologische Gemeinschaftspraxis |
Abenhardt W.,Munchner Onkologische Praxis |
Dorfel S.,Onkozentrum |
Meyer D.,Hamatologisch Onkologische Schwerpunktpraxis |
And 4 more authors.
Hematological Oncology | Year: 2015
Various treatment options exist for patients with chronic lymphocytic leukaemia (CLL). Clinical registries provide insight into routine treatment and identify changes in treatment over time. The Tumour Registry Lymphatic Neoplasms prospectively collects data on the treatment of patients with lymphoid B-cell neoplasm as administered by office-based haematologists in Germany. Data on patient and tumour characteristics, co-morbidities, systemic treatments, and outcome parameters are recorded. Eight hundred and six patients with CLL were recruited between May 2009 and August 2013. At the start of first-line treatment, median age was 71years, 64% were male, and 44% had a Binet stage C disease. The most frequently used first-line/second-line regimens were bendamustine+rituximab (BR, 56%/55%), fludarabine+cyclophosphamide+rituximab (FCR, 22%/11%), and bendamustine (B, 5%/9%). Chlorambucil was used in only 7% (first-line) and 6% (second-line) of patients. Patients treated with FCR were younger and healthier than patients treated with BR. Overall, 91% of first-line treatments were successful (40% complete response). Real-life patient populations differ considerably from patients treated in randomized controlled trials. BR and FCR dominate the first-line and second-line treatments of CLL by office-based haematologists in Germany. Future analysis will investigate progression-free and overall survival times. © 2014 The Authors. Hematological Oncology Published by John Wiley & Sons, Ltd. © 2015 John Wiley & Sons, Ltd.