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Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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At least 145 records · Page 8Linked to original sources
PubMed2004

Epidermal growth factor receptor: a promising target in solid tumours.

The epidermal growth factor receptor (EGFR) is expressed in a wide variety of solid tumours. It has been demonstrated that the EGFR-associated signaling pathway plays an important role in carcinogenesis and cancer progression. In the new therapeutic paradigm of molecular-targeted cancer therapy, interference with intracellular signaling cascades is an appealing treatment approach. Inhibitory strategies under study include monoclonal antibodies, tyrosine kinase inhibitors, EGFR-ligand conjugates, EGFR immunoconjugates, and antisense oligonucleotides. Many of these strategies have demonstrated efficacy against EGFR-expressing tumour cells in preclinical studies, prompting a large number of clinical trials. In particular, clinical studies using monoclonal antibody blockade and EGFR tyrosine kinase inhibitors have suggested that EGFR blockade is a well-tolerated and effective treatment strategy; however, more trials are needed to precisely define how these agents will fit into modern cancer care.

Animals↗
PubMed2004

Current concepts and review of efalizumab in the treatment of psoriasis.

Efalizumab is a recombinant humanized monoclonal IgG1 antibody that targets CD11a, a cell surface protein that plays a key role in the T-cell-mediated steps leading to the pathogenesis of psoriasis. The efficacy and safety of efalizumab have been studied extensively in patients with moderate to severe chronic plaque psoriasis. Clinical trial data developed in several large phase 3 studies have demonstrated that efalizumab rapidly improves both physician- and patient-assessed measures of clinical efficacy, and that the observed changes are sustainable over extended periods of continuous treatment, with a favorable safety profile. Efalizumab represents a new therapeutic option for the long-term management of moderate to severe chronic plaque psoriasis.

Antibodies, Monoclonal↗
PubMed2005

Proposal of a morphologic bone marrow response score for imatinib mesylate treatment in chronic myelogenous leukemia.

Cytogenetic and molecular analyses are essential disease-monitoring parameters in chronic myelogenous leukemia (CML) treated with imatinib. However, a bone marrow morphologic response has not been defined. We reviewed bone marrow histology and cytology of 39 imatinib-treated patients with CML over 49 weeks and introduced a morphologic response score. A significant positive correlation with a complete cytogenetic response was shown for absence of dry tap (P = .04) and abnormal megakaryocytes (P < 0.001), normalization of cellularity (P = .001) and reduction of fibrosis (P = .01), myelopoiesis:erythropoiesis index (P = .001), blast (P = .001) and basophil count (P < 0.001). The morphologic score integrating these parameters showed an early and late correlation with cytogenetic response. In conclusion, morphologic criteria for complete cytogenetic response in patients with CML treated with imatinib can be defined. Persistent high-level morphologic abnormalities herald early on a high likelihood to fail treatment and call for more intense or alternative therapy.

Adult↗
PubMed2005

[Proteasome inhibitors].

INTRODUCTION: Proteasome is involved in cell cycle and apoptosis regulation. Its deregulation could participate to oncogenesis. EXEGESIS: Bortezomib is the first proteasome inhibitor to reach clinical development. Its main adverse events are asthenia, thrombocytopenia and cumulative neurotoxicity which can limits long term use. As single agent, bortezomib displays antitumoral effects in refractory multiple myeloma and mantle cell lymphoma but has only modest activity in solid tumors. Preclinical data suggest that bortezomib could enhance antitumor activity of cytotoxics. CONCLUSION: Proteasome inhibition is a promising therapeutic pathway, especially in lymphoid malignancies.

Adenocarcinoma↗
PubMed2005

The current role of chemotherapy in metastatic hormone-refractory prostate cancer.

Since the publication of the Southwest Oncology Group (SWOG) 99-16 and TAX 327 studies, which demonstrated a survival benefit for docetaxel-based therapy, clinicians for the first time have a therapy to offer men with metastatic prostate cancer that is not merely palliative in its effects. Phase 2 and phase 3 trials are now building on the findings of SWOG 99-16 and TAX 327 by evaluating the potential of combination taxane-based therapies, such as docetaxel plus high-dose calcitriol, docetaxel-estramustine-bevacizumab, and docetaxel-thalidomide. The optimal timing of docetaxel-based chemotherapy is still unknown, as there are no prospective clinical trial data to indicate whether earlier treatment (eg, at the time of prostate-specific antigen failure) is more or less effective than later treatment (eg, in metastatic and/or symptomatic disease).

Androgen Antagonists↗
PubMed1997

Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.

PURPOSE: Promising results from new approaches such as radiosurgery or stereotactic surgery of brain metastases have recently been reported. Are these results due to the therapy alone or can the results be attributed in part to patient selection? An analysis of tumor/patient characteristics and treatment variables in previous Radiation Therapy Oncology Group (RTOG) brain metastases studies was considered necessary to fully evaluate the benefit of these new interventions. METHODS AND MATERIALS: The database included 1200 patients from three consecutive RTOG trials conducted between 1979 and 1993, which tested several different dose fractionation schemes and radiation sensitizers. Using recursive partitioning analysis (RPA), a statistical methodology which creates a regression tree according to prognostic significance, eighteen pretreatment characteristics and three treatment-related variables were analyzed. RESULTS: According to the RPA tree the best survival (median: 7.1 months) was observed in patients < 65 years of age with a Karnofsky Performance Status (KPS) of at least 70, and a controlled primary tumor with the brain the only site of metastases. The worst survival (median: 2.3 months) was seen in patients with a KPS less than 70. All other patients had relatively minor differences in observed survival, with a median of 4.2 months. CONCLUSIONS: Based on this analysis, we suggest the following three classes: Class 1: patients with KPS > or = 70, < 65 years of age with controlled primary and no extracranial metastases; Class 3: KPS < 70; Class 2- all others. Using these classes or stages, new treatment techniques can be tested on homogeneous patient groups.

Adult↗
PubMed2002

Clinical trial designs for targeted agents.

With an increasing number of targeted agents available for testing, clinical trials must be rationally designed based on sound knowledge of the molecular mechanisms linking target and disease, fortified by strong preclinical data demonstrating how this relationship is modified by the targeted agent. Patients and resources are precious and should be expended judiciously on clinical trials that are well planned. Although traditional trial designs and endpoints may not be adequate for developing contemporary targeted drugs, transiting directly from phase I to phase III testing should be avoided except in distinct circumstances. Increased research efforts should be spent on the prospective evaluation and validation of novel biologic endpoints and innovative clinical designs, such that promising targeted agents can be effectively developed to benefit the care of cancer patients.

Animals↗
PubMed2003

Early microdose drug studies in human volunteers can minimise animal testing: Proceedings of a workshop organised by Volunteers in Research and Testing.

Testing the safety and efficacy of a successful human medicine involves many laboratory animals, which can sometimes be subjected to considerable suffering and distress. Also, it is necessary to extrapolate from the test species to humans. UK and European legislation requires that Replacement, Reduction and Refinement of animal procedures (the Three Rs) are implemented wherever possible. Over the last decade, there has been substantial progress with applying in vitro and in silico methods to both drug efficacy and safety testing. This paper is a report of the discussions and recommendations arising from a workshop on the role that might be played by human volunteer studies in the very early stages of drug development. The workshop was organised in November, 2001 by Volunteers in Research and Testing, a group of individuals in the UK which launched an initiative in 1994 to identify where and how human volunteers can participate safely in biomedical studies to replace laboratory animals. It was considered that conducting pre-Phase I very low dose human studies (sub-toxic and below the dose threshold for measurable pharmacological or clinical activity) could enable drug candidates to be assessed earlier for in vivo human pharmacokinetics and metabolism. Moreover, accelerator mass spectrometry (AMS), nuclear magnetic resonance (NMR) spectroscopy and positron emission tomography (PET) are potentially useful spectrometric and imaging methods that can be used in conjunction with such human studies. Some, limited animal tests would still be required before pre-Phase I microdose studies, to take account of the potential risk posed by completely novel chemicals. The workshop recommended that very early volunteer studies using microdoses should be introduced into the drug development process in a way that does not compromise volunteer safety or the scientific quality of the resulting safety data. This should improve the selection of drug candidates and also reduce the likelihood of later candidate failure, by providing in vivo human ADME data, especially for pharmacokinetics and metabolism, at an earlier stage in drug development than is currently the case.

Animal Testing Alternatives↗
PubMed2002

Future treatment options with capecitabine in solid tumours.

The oral fluoropyrimidine, capecitabine is attracting great interest in the context of tumour-selective therapy and rationally designed combination regimens. Agents such as taxanes upregulate thymidine phosphorylase (TP), and there is therefore a clear rationale for their combination with capecitabine. Preclinical studies of capecitabine/taxane combination therapy demonstrated synergistic antitumour activity and phase I studies showed encouraging efficacy. Therefore, a randomised, phase III trial (docetaxel versus docetaxel/capecitabine) has been initiated in anthracycline-refractory metastatic breast cancer patients. Recruitment is complete. In colorectal cancer, capecitabine/oxaliplatin combination therapy is promising and a phase I, dose-finding trial has been conducted in patients with refractory metastatic solid tumours. A similar trial has evaluated capecitabine/irinotecan combination treatment. Capecitabine is also being investigated as adjuvant therapy for colorectal and breast cancers. The primary objective of the ongoing X-ACT trial in almost 2000 Dukes' C colon cancer patients is to demonstrate at least equivalent disease-free survival between capecitabine and the Mayo Clinic regimen. In addition, the CALGB is planning a randomised, phase III trial of capecitabine versus doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil (CMF) as adjuvant treatment in high-risk, node-negative breast cancer patients aged >65 years.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Measuring the clinical response. What does it mean?

The clinical response to treatment is an important indicator of the therapeutic effect of anticancer agents. Its value and interpretation has to be carefully considered within the context that it is used. In daily practice, response assessment is combined with other indicators of the patient's condition to contribute to the decision-making process. In clinical trials, it is widely used to identify and quantify the anti-tumour activity of new agents. In this context, response evaluation is conducted on the basis of strict predefined criteria such as the World Health Organization (WHO) or Response Evaluation Criteria In Solid Tumors (RECIST) criteria. The RECIST criteria have recently been proposed and offer a detailed guidance to perform a response evaluation. Clinical response is also used as an indicator of therapeutic efficacy in combination with other indicators. Its value as a surrogate indicator of a survival benefit remains unclear in most instances and can hardly be established within the framework of a single randomised trial. With the development of new anticancer agents that behave differently to cytotoxics, clinical benefit will have to integrate concepts of disease stabilisation or time to progression. Over the next decade, oncologists will be able to assess the biological response before the clinical response, and a lot of work and energy will have to be dedicated to assess the predictive and, possibly, the prognostic value of the biological response with regard to the clinical response, as well as more definitive measures of clinical benefit.

Antineoplastic Agents↗
PubMed2002

Viral oncolysis.

Although the concept of using viruses as antineoplastic agents dates back nearly a century, recent advances in the fields of molecular biology, genetics, and virology have enabled investigators to engineer viruses with greater potency and tumor specificity. Further enhancements involve arming these viruses with therapeutic transgenes, and combining the traditional modalities of chemotherapy and radiation therapy with oncolytic viral therapy in hopes of reducing the chance of developing resistant tumor cell clones. Another means of augmenting the antineoplastic effect of these viruses involves modulating the immune response to minimize antiviral immunity, while at the same time maximizing antitumor immunity. A better understanding of mechanisms that viruses use to overcome cellular defenses to achieve robust replication within the cell will lead to development of oncolytic viruses with better tumor specificity and reduced toxicity. Initial clinical studies have shown that oncolytic viral therapy for metastatic disease is safe and well tolerated. In addition, using similar genetic modification strategies, these viruses have demonstrated antineoplastic effects in humans similar to those seen in preclinical animal models.

Adenoviridae↗