Expert Opinion on Investigational Drugs | Year: 2012
Introduction: Drug development is a complex and risky enterprise. Clinical development must be a thoroughly paced process sequenced by clinical and developmental questions logically ordered. Drug development parameters are changing due to better insights in system biology and mechanisms of actions. Therefore, there is a need to revisit how clinical trials are designed and sequenced. Areas covered: In the context of this paper, the development of glufosfamide is placed in perspective of possible new trends for more optimal drug development. Glufosfamide is an alkylating agent with a favorable safety profile as its metabolic activation does not lead to the release of toxic metabolites such as acrolein. In addition, its cellular uptake mediated through the transmembrane receptors of glucose makes it an attractive agent for the treatment of highly proliferative tumors cells. These observations have served the rationale to bring this agent to the clinic from Phase I up to Phase III with a focus on pancreatic cancer. The pathways for its development have been challenging due in part to the fact that there is no proof of mechanism-based study for any alkylating agent, even those used in the clinic. Expert opinion: Solid mechanism and translational research-based clinical trials providing evidence on the mechanism of action and how the agent interacts with the biology of the targeted disease are today an absolute requirement for the development of new agents. Optimal clinical trial design must complement system biology understanding so that 'trials designed to learn' may give robust grounds to 'clinical trials designed to conclude'. © 2012 Informa UK, Ltd. Source
Joly F.,University of Caen Lower Normandy |
McAlpine J.,University of British Columbia |
Nout R.,Leiden University |
Avall-Lundqvist E.,Karolinska University Hospital |
And 2 more authors.
International Journal of Gynecological Cancer | Year: 2014
Background: There is increasing recognition that quality of life (QoL) and patientreported outcomes (PROs) are of fundamental importance and particularly relevant given the relatively high likelihood of long-term survival in most women with endometrial cancer (EC). However, there has been relatively little research focused on this topic. Our objective was to analyze our current knowledge and identify research questions to be included in the design of next clinical trials. Methods: Analyze and critically assess reported clinical trials in EC that have included QoL and PROs as primary or secondary end points. Results: Surgery has a significant impact on physical and functional domains of QoL particularlyinthefirst6months after diagnosis. Minimally invasive surgeryisassociated with less acute morbidity than open procedures and this persists over time. Lymphadenectomy is associated with increased incidence of lymphedema, important late effect. Adjuvant external irradiation may cause gastrointestinal and genitourinary symptoms that impact on physical functioning and which can persist over time.Incontrast, vaginal brachytherapy has less toxicity and fewer late effects than external irradiation. The impact of treatment on sexuality has been poorly evaluated in EC survivors. There are few published data on QoL and PROs in patients treated with chemotherapy and the long-term impact has not been addressed. There is no evidence that palliative chemotherapy reduces symptoms and improves QoL. There are very few longitudinal studies on survivorship that is an important concern in EC survivors. Conclusions: Although there have been some studies addressing QoL and PROs in EC, we have identified deficiencies and gaps in our knowledge. Careful consideration of QoL and PROs end points and how to include them in clinical trials will result in a better appreciation of how treatments can impact on patients QoL and lead to conduct interventions to reduce late effects. Copyright © 2014 by IGCS and ESGO. Source
Monitoring the response of bone metastases to treatment with Magnetic Resonance Imaging and nuclear medicine techniques: A review and position statement by the European Organisation for Research and Treatment of Cancer imaging group
Lecouvet F.E.,Catholic University of Louvain |
Lecouvet F.E.,Cliniques universitaires Saint Luc |
Talbot J.N.,University Pierre and Marie Curie |
Messiou C.,Royal Marsden Hospital |
And 4 more authors.
European Journal of Cancer | Year: 2014
Assessment of the response to treatment of metastases is crucial in daily oncological practice and clinical trials. For soft tissue metastases, this is done using computed tomography (CT), Magnetic Resonance Imaging (MRI) or Positron Emission Tomography (PET) using validated response evaluation criteria. Bone metastases, which frequently represent the only site of metastases, are an exception in response assessment systems, because of the nature of the fixed bony defects, their complexity, which ranges from sclerotic to osteolytic and because of the lack of sensitivity, specificity and spatial resolution of the previously available bone imaging methods, mainly bone scintigraphy. Techniques such as MRI and PET are able to detect the early infiltration of the bone marrow by cancer, and to quantify this infiltration using morphologic images, quantitative parameters and functional approaches. This paper highlights the most recent developments of MRI and PET, showing how they enable early detection of bone lesions and monitoring of their response. It reviews current knowledge, puts the different techniques into perspective, in terms of indications, strengths, weaknesses and complementarity, and finally proposes recommendations for the choice of the most adequate imaging technique. © 2014 The Authors. Source
News Article | November 15, 2015
Based on the results of EORTC trial 18071, the FDA expanded the approval of Yervoy (ipilimumab) in melanoma to include adjuvant treatment of patients with stage 3 melanoma at high risk of recurrence following complete resection.
News Article | September 8, 2016
A new study represents a long-term analysis of prognostic factors among some patients with breast cancer who were treated with breast-conserving therapy in the EORTC "boost no boost" trial, which evaluated the influence of a "boost" dose in radiotherapy.