PubMed | Oncologisch Centrum, UZ Brussel, ASZ, Consultant in Statistics and University Hospitals Leuven
Type: | Journal: Clinical colorectal cancer | Year: 2016
This study aims to evaluate the relevance of geriatric assessment (GA) in older patients with colorectal cancer (CRC) and to study functional status (FS) and chemotherapy-related toxicity during treatment.Patients with CRC aged 70 years were evaluated at baseline using a GA. Results were communicated to the treating physician. At 2 to 3 months follow-up, FS was reassessed, and chemotherapy-related toxicity was recorded.A total of 193 patients, with a median age of 77 years, were included. GA was abnormal in 75% and revealed unknown problems in 40%. Treatment was altered in 37% based on clinical assessment. GA led to geriatric interventions in 9 patients (5%) and additionally influenced treatment in 1 patient. At follow-up (n= 164), functional decline was observed in 29 patients (18%) for activities of daily living (ADL) and in 60 patients (37%) for instrumental activities of daily living (IADL). Baseline IADL, depression, fatigue, and cognition were predictors for ADL decline, whereas no predictors for IADL decline could be identified. In the 109 patients receiving chemotherapy, stage and baseline fatigue were predictive for grade 3/4 hematologic toxicity, and baseline ADL, fatigue, and nutrition were predictive for grade 3/4 nonhematologic toxicity.Although GA identified previously unknown problems in more than one-third of older CRC patients, the impact on interventions or treatment decisions was limited. Baseline GA parameters may predict functional decline and chemotherapy-related toxicity. Education of physicians treating older patients with CRC is an essential step in the implementation of GA and subsequent interventions.
PubMed | Vesalius Research Center, University Hospitals Leuven, Dienst Medische Oncologie, Dienst Oncologie and Oncologisch Centrum
Type: | Journal: BMC pharmacology & toxicology | Year: 2015
This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer.Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival.The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C>T; p=0.023, OR=1.71, 95% CI=1.07-2.71), rs363717 (ABCA1, A>G; p=0.002, OR=2.08, 95% CI=1.32-3.27) and rs11615 (ERCC1, T>C; p=0.031, OR=1.61, 95% CI=1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C>G; p=0.004, OR=0.51, 95% CI=0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T>C; p=0.025, OR=4.99, 95% CI=1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A>G; p=0.039, OR=0.60, 95% CI=0.37-0.98), rs1695 (ABCC1, A>G; p=0.017, OR=0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G>A; p=0.042, OR=0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G>C; p=0.011, OR=2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G>A) G-allele had a prolonged platinum-free interval (p=0.016).Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.
Coiffier B.,Service dHematologie |
Radford J.,University of Manchester |
Bosly A.,Clinique Universitaires Ucl Of Mont Godinne |
Martinelli G.,Instituto Europeo Of Oncologia |
And 13 more authors.
British Journal of Haematology | Year: 2013
This international, multicentre phase II study was conducted to assess ofatumumab, a human anti-CD20 monoclonal antibody, in patients with relapsed/progressive diffuse large B-cell lymphoma (DLBCL) who were ineligible for autologous stem cell transplantation (TI) or who had relapse/progression after transplantation (PT). Eighty-one patients received ofatumumab 300 mg intravenously (IV) on Day 1, followed by seven weekly IV infusions of 1000 mg. Patients in the TI and PT groups had received a median of 3 (range, 1-7) and 5 (range, 2-7) prior therapies, respectively. One-third of patients did not respond to the last prior therapy, and 53% had failed two or more rituximab-containing therapies. Overall response rate was 13% for the TI group (seven partial responses) and 8% for the PT group (two complete responses). Median progression-free survival was 2·6 months, and median duration of response was 9·5 months. The most common Grade 3-4 adverse events were neutropenia (11%), leucopenia (6%), lymphopenia (6%) and thrombocytopenia (6%). Sixteen deaths have been reported, with disease progression as the most common cause of death. In conclusion, ofatumumab monotherapy was well tolerated and provided clinical benefit to some DLBCL patients in this study. This trial was registered at www.clinicaltrials.gov (NCT00622388). © 2013 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.
Schuler M.,University of Duisburg - Essen |
Awada A.,Free University of Colombia |
Harter P.,Dr Horst Schmidt Kliniken GmbH |
Canon J.L.,Grand Hopital de Charleroi |
And 16 more authors.
Breast Cancer Research and Treatment | Year: 2012
Afatinib (BIBW 2992) is an ErbB-family blocker that irreversibly inhibits signaling from all relevant ErbB-family dimers. Afatinib has demonstrated preclinical activity in human epidermal growth factor receptor HER2 (ErbB2)-positive and triple-negative xenograft models of breast cancer, and clinical activity in phase I studies. This was a multicenter phase II study enrolling patients with HER2-negative metastatic breast cancer progressing following no more than three lines of chemotherapy. No prior epidermal growth factor receptor-targeted therapy was allowed. Patients received 50-mg afatinib once daily until disease progression. Tumor assessment was performed at every other 28-day treatment course. The primary endpoint was clinical benefit (≥B) for ≥4 treatment courses in triple-negative (≥ohort A) metastatic breast cancer (TNBC) and objective responses measured by Response Evaluation Criteria in Solid Tumors in patients with HER2-negative, estrogen receptor-positive, and/or progesterone receptorpositive breast cancer (≥ohort B). Fifty patients received treatment, including 29 patients in Cohort A and 21 patients in Cohort B. No objective responses were observed in either cohort. Median progression-free survival was 7.4 and 7.7 weeks in Cohorts A and B, respectively. Three patients with TNBC had stable disease for C4 treatment courses, one of them for 12 courses (median 26.3 weeks; range 18.9-47.9 weeks). The most frequently observed afatinib-associated adverse events (AEs) were gastrointestinal and skin-related side effects, which were manageable by symptomatic treatment and dose reductions. Afatinib pharmacokinetics were comparable to those observed in previously reported phase I trials. In conclusion, afatinib had limited activity in HER2-negative breast cancer. AEs were generally manageable and mainly affected the skin and the gastrointestinal tract. © The Author(s) 2012. This article is published with open access at Springerlink.com.
Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer
Wildiers H.,University Hospitals Leuven |
Fontaine C.,Oncologisch Centrum |
Vuylsteke P.,Sint Elisabeth Hospital |
Martens M.,Sint Elisabeth Hospital |
And 6 more authors.
Breast Cancer Research and Treatment | Year: 2010
The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) ≥5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III-IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of ≥5 months after an objective response to taxanes. Furthermore, toxicity was significant. © 2010 Springer Science+Business Media, LLC.
PubMed | Jules Bordet Institute, Oncologisch Centrum, Free University of Colombia and Vrije Universiteit Brussel
Type: Journal Article | Journal: Clinical genetics | Year: 2016
Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs), and conventional chemotherapy is the only effective systemic treatment. Germline BRCA1/2 mutations are found in approximately 15% of TNBC patients. In the past, we have documented pathogenic mutations in BARD1, a BRCA1 interacting protein, in families at high risk for BC. In this study, we have analyzed germline DNA from 61 estrogen receptor negative patients (of which 42 were TNBC) for the presence of mutations in the BRCA1, BRCA2 and BARD1 gene. BRCA1/2 mutations were found in 8 out of 42 (19%) TNBC patients, but not in the ER-/HER2+ cohort. We also found four good candidate pathogenic BARD1 mutations in the TNBC cohort, including two protein-truncating mutations (p.Gln564Ter and p.Arg641Ter). Our data suggest that TNBC patients are enriched for pathogenic BARD1 germline mutations as compared to control samples and high BC risk families. Ten of the 42 investigated TNBC patients carry a BRCA pathway mutation (in BRCA1, BRCA2 or BARD1) rendering them susceptible to homologous recombination deficiency. These patients should become eligible for exploring the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors.
Verschelden G.,VUB |
Van Eetvelde E.,Dienst Oncologische Chirurgie |
Djedaimi H.,Dienst Anatomopathologie |
De Greve J.,Oncologisch Centrum
Tijdschrift voor Geneeskunde | Year: 2015
A leiomyosarcoma of the vena cava is a rare but potentially lethal tumor. It is more common in women around the 6th decade and is most frequently localised in the mid vena cava inferior. An oncological resection is the only way to provide a long term remission. Adjuvant therapy, based on radio and/or chemotherapy may prolong progression-free survival, but without hard evidence. Illustrated by a the medical history of a 51-year-old male patient, the current knowledge on leiomyosarcoma is discussed. Additionally, the specific characteristics of a primary leiomyosarcoma of the inferior vena cava are described. © 2015, Tijdschrift voor Geneeskunde. All rights reserved.
Schallier D.,Oncologisch Centrum |
Decoster L.,Oncologisch Centrum |
Fontaine C.,Oncologisch Centrum |
De Greve J.,Oncologisch Centrum
Anticancer Research | Year: 2010
Background: Pemetrexed-induced eyelid edema is a rare side-effect of pemetrexed treatment. Patients and Methods: Retrospective analysis of the incidence and severity of eyelid edema was conducted in patients treated with pemetrexed in a single institution. Results: Eighty-six patients received pemetrexed-containing chemotherapy either as a single agent (45 patients) or in combination with cis- or carboplatin (41 patients). Two patients (2.3%) with stage IV non-small cell lung cancer (NSCLC) presented the edema typically localized in the lower eyelid after first-line treatment with carboplatin-pemetrexed. The edema remained identical in both patients during treatment and regressed in one patient in whom treatment was withdrawn. No other localizations of edema were observed in these patients. Conclusion: Pemetrexed-induced eyelid edema may be more frequent than originally reported. The physiopathological mechanism and, as a consequence, the treatment and/or prevention of this apparently benign sideeffect remains unknown.