Home About us Contact
|
Home About us Contact | ||
|
|
||
Phase III Clinical Trials (phase + iii_clinical_trials)
Selected AbstractsDelivery of endostatin in experimental cancer therapyINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 6 2002Dag R. Sorensen Summary. Endostatin, the 20 kDa C-terminal fragment of collagen XVIII, has been shown to be an effective inhibitor of tumour angiogenesis and growth in different experimental systems and is currently in Phase II/III clinical trials. One challenging aspect of anti-angiogenic treatment is the mode of delivery of the active compound. In this paper we review some of the basic knowledge of endostatin and look specifically into the different possible ways in which endostatin may be administered. [source] The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trialsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009C. VEYRAT-FOLLET Summary.,Background: Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events. Objectives: To characterize the population pharmacokinetic profile of idraparinux in patients enrolled in van Gogh and Amadeus Phase III clinical trials. Patients and methods: Idraparinux was administered once-weekly subcutaneously at a dose of 2.5 mg, or 2.5 mg (first dose) and then 1.5 mg for patients with severe renal insufficiency (creatinine clearance <30 mL min,1). A population pharmacokinetic model was developed using data from 704 patients with acute deep-vein thrombosis or pulmonary embolism, 1310 patients suffering from atrial fibrillation, and 40 healthy subjects. Potential covariates analyzed included demographics (age, sex, weight and ethnicity), and serum creatinine and creatinine clearance determinations. Results: A three-compartment model best described idraparinux pharmacokinetics, with interindividual variability on clearance, central volume of distribution, and absorption rate constant; residual variability was low. Typical clearance, central volume of distribution, absorption rate constant and volume of distribution at steady-state were 0.0255 L h,1, 3.36 L, 1.37 h and 30.8 L, respectively. Peak concentration was reached at 2.5 h. The terminal half-life was 66.3 days and time to steady-state was 35 weeks. At steady-state, exposures were similar for patients without and with severe renal impairment receiving adjusted-dose. Creatinine clearance was the most important covariate affecting idraparinux clearance. The particular characteristics of idraparinux , rapid onset of action and long-acting anticoagulant effect , offer interesting clinical perspectives currently under investigation with idrabiotaparinux, the reversible biotinylated form of idraparinux. [source] Psychometric performance and clinical meaningfulness of the Patient Assessment of Constipation , Quality of Life questionnaire in prucalopride (RESOLOR®) trials for chronic constipationNEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2010D. Dubois Abstract Background, The Patient Assessment of Constipation,Quality of Life (PAC-QOL) is a self-reported questionnaire measuring health-related quality of life (HRQL) of constipated patients and was used as secondary endpoint in three identical double-blind, randomized, placebo-controlled Phase III clinical trials. These 12-week trials in subjects with severe chronic constipation evaluated the effects of prucalopride, a selective 5-HT4 agonist given orally once daily. Methods, To consolidate the main treatment effect results observed in the prucalopride trial populations, analyses were undertaken on the pooled data of the three trials to confirm the psychometric properties of the PAC-QOL and to provide guidance for the interpretation of the clinical significance of its scores. Key Results, The evaluation of the psychometric properties confirmed the PAC-QOL reliability, validity and responsiveness to measure the impact of chronic constipation symptoms on HRQL in the prucalopride trials. The 1-point improvement in PAC-QOL scores used as target response level for the main treatment effect analyses was validated as a relevant definition of response for treatment group comparisons. Cumulative distribution curves, drawn for each treatment group to provide more complete information on treatment effects than single minimal important difference point estimates, demonstrated consistent superior effects of prucalopride over placebo on all PAC-QOL scores. Conclusions & Inferences, The PAC-QOL questionnaire is a useful measurement tool to assess, from a patient perspective, the potential therapeutic value of chronic constipation treatments in clinical trials and, by directly reflecting the patient's own perspective on constipation and its treatment, eventually also for informing daily medical practice. [source] Dofequidar fumarate sensitizes cancer stem-like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP-mediated drug exportCANCER SCIENCE, Issue 11 2009Ryohei Katayama The ATP-binding cassette (ABC) transporters (ABC-T) actively efflux structurally and mechanistically unrelated anticancer drugs from cells. As a consequence, they can confer multidrug resistance (MDR) to cancer cells. ABC-T are also reported to be phenotypic markers and functional regulators of cancer stem/initiating cells (CSC) and believed to be associated with tumor initiation, progression, and relapse. Dofequidar fumarate, an orally active quinoline compound, has been reported to overcome MDR by inhibiting ABCB1/P-gp, ABCC1/MDR-associated protein 1, or both. Phase III clinical trials suggested that dofequidar had efficacy in patients who had not received prior therapy. Here we show that dofequidar inhibits the efflux of chemotherapeutic drugs and increases the sensitivity to anticancer drugs in CSC-like side population (SP) cells isolated from various cancer cell lines. Dofequidar treatment greatly reduced the cell number in the SP fraction. Estimation of ABC-T expression revealed that ABCG2/breast cancer resistance protein (BCRP) mRNA level, but not the ABCB1/P-gp or ABCC1/MDR-associated protein 1 mRNA level, in all the tested SP cells was higher than that in non-SP cells. The in vitro vesicle transporter assay clarified that dofequidar had the ability to suppress ABCG2/BCRP function. Dofequidar treatment sensitized SP cells to anticancer agents in vitro. We compared the antitumor efficacy of irinotecan (CPT-11) alone with that of CPT-11 plus dofequidar in xenografted SP cells. Although xenografted SP tumors showed resistance to CPT-11, treatment with CPT-11 plus dofequidar greatly reduced the SP-derived tumor growth in vivo. Our results suggest the possibility of selective eradication of CSC by inhibiting ABCG2/BCRP. (Cancer Sci 2009) [source] REVIEW: ,-Secretase Inhibitors for the Treatment of Alzheimer's Disease: The Current StateCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 5 2010Francesco Panza SUMMARY Aims: Drugs currently used for the treatment of Alzheimer's disease (AD) partially stabilize patients' symptoms without modifying disease progression. Brain accumulation of oligomeric species of ,-amyloid (A,) peptides, the principal components of senile plaques, is believed to play a crucial role in the development of AD. Based on this hypothesis, huge efforts are being spent to identify drugs able to interfere with proteases regulating A, formation from amyloid precursor protein (APP). This article briefly reviews the profile of ,-secretase inhibitors, compounds that inhibit ,-secretase, the pivotal enzyme that generates A,, and that have reached the clinic. Discussion: Several classes of potent ,-secretase inhibitors have been designed and synthesized. Preclinical studies have indicated that these compounds are able to lower brain A, concentrations and, in some cases, reduce A, plaque deposition in transgenic mouse models of AD. The most developmentally advanced of these compounds is semagacestat, presently in Phase III clinical trials. In animals, semagacestat reduced A, levels in the plasma, cerebrospinal fluid (CSF), and the brain. However, studies have not reported on its cognitive effects. Studies in both healthy volunteers and patients with AD have demonstrated a dose-dependent inhibition of plasma A, levels, and a recent study in healthy subjects demonstrated a robust, dose-dependent inhibition of newly generated A, in the CSF after single oral doses. Conclusions: Unfortunately, ,-secretase inhibitors may cause intestinal goblet cell hyperplasia, thymus atrophy, decrease in lymphocytes, and alterations in hair color, effects associated with the inhibition of the cleavage of Notch, a protein involved in cell development and differentiation. Nevertheless, at least other two promising ,-secretase inhibitors are being tested clinically. This class of drugs represents a major hope to slow the rate of decline of AD. [source] Colesevelam lowers glucose and lipid levels in type 2 diabetes: the clinical evidenceDIABETES OBESITY & METABOLISM, Issue 5 2010Vivian A. Fonseca Simultaneous control of blood glucose and other risk factors such as hypertension and dyslipidaemia is essential for reducing the risk of complications associated with type 2 diabetes mellitus (T2DM). As relatively few patients with T2DM have their risk factors managed to within the limits recommended by the American Diabetes Association, American College of Endocrinology or National Cholesterol Education Program Adult Treatment Panel III guidelines, treatment that can simultaneously control more than one risk factor is of therapeutic benefit. Clinical studies have shown that bile acid sequestrants have glucose-lowering effects in addition to their low-density lipoprotein cholesterol-lowering effects in patients with T2DM. The bile acid sequestrant colesevelam hydrochloride is approved as an adjunct to antidiabetes therapy for improving glycaemic control in adults with T2DM. This review examines data from three phase III clinical trials that evaluated the glucose- and lipid-lowering effects of colesevelam when added to the existing antidiabetes treatment regimen of patients with T2DM. [source] CETP inhibition in cardiovascular risk management: a critical appraisalEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2007R. P. F. Dullaart Abstract In view of the cardioprotective effect of high-density lipoproteins (HDL) and the limited effects of statin and fibrate therapy on HDL cholesterol, it is clinically relevant to test whether pharmacological treatment aimed at raising HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a new therapeutic target, because the cholesteryl ester transfer process lowers HDL cholesterol and contributes to an atherogenic lipoprotein profile, particularly when plasma triglycerides are high. Clinical evidence suggests that coronary artery calcification as well as intima media thickness is positively related to plasma cholesteryl ester transfer, and that high plasma CETP concentration is associated with increased cardiovascular risk in hypertriglyceridaemia. However, CETP could also have anti-atherogenic potential, since it provides a potentially beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In addition, CETP could also favourably stimulate peripheral cell cholesterol removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a high CETP level may confer lower cardiovascular risk in the context of low triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib elicit a marked rise in HDL cholesterol of up to 34% and 91,106%, respectively. The effectiveness of these drugs on (intermediate) clinical outcome measures is currently being tested in large-scale phase III clinical trials, with torcetrapib being only evaluated in combination therapy with atorvastatin. When and how to use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major challenge. We propose that low HDL cholesterol in the context of high triglycerides, such as found in type 2 diabetes mellitus, could become an important indication area for this new class of drugs. [source] StriantÔ SR: a novel, effective and convenient testosterone therapy for male hypogonadismINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 11 2004M. Korbonits Summary StriantÔ SR (marketed as Striant® in the US) is a novel sustained-release mucoadhesive buccal testosterone tablet for the treatment of male hypogonadism. StriantÔ SR restores serum testosterone concentrations to the physiological range within 4 h of application, and steady-state concentrations are achieved within 24 h of twice-daily dosing. In phase III clinical trials, 87,97% of patients using StriantÔ SR achieved 24-h-averaged serum testosterone concentrations within the normal range. In a comparative study, StriantÔ SR was more likely to restore testosterone concentrations to the physiological range than Andropatch®. In a small study, StriantÔ SR produced steady-state testosterone concentrations comparable with those achieved with a testosterone gel (50 mg testosterone). StriantÔ SR was well tolerated, with a low incidence of adverse events and a low discontinuation rate (3.5%) due to adverse events in phase III studies. StriantÔ SR is an effective, well-tolerated, convenient and discreet treatment for male hypogonadism. [source] The Endocannabinoid System and the Control of Glucose HomeostasisJOURNAL OF NEUROENDOCRINOLOGY, Issue 2008R. Nogueiras Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. The first selective CB1 receptor antagonist, rimonabant, which has already successfully completed phase III clinical trials, led to sustained weight loss and a reduction in waist circumference. Patients treated with rimonabant also demonstrated statistically significant improvement in high-density lipoprotein cholesterol levels, triglyceride levels and insulin resistance, as well as a reduced overall prevalence of metabolic syndrome. Currently, one of the most discussed aspects of endocannabinoid system function is to what extent the endocannabinoid system might affect metabolism independently of its control over body weight and food intake. Specifically, a food-intake- and body-weight-independent role in the regulation of glucose homeostasis and insulin sensitivity could have major impact on the potential of drug candidates targeting the endocannabinoid system for the prevention and treatment of metabolic syndrome. This review summarises the effects of the endocannabinoid system on glucose homeostasis and insulin sensitivity. [source] Distribution, metabolism, and excretion of a novel surface-active agent, purified poloxamer 188, in rats, dogs, and humansJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 9 2002J. Michael Grindel Abstract Purified poloxamer 188 (PP188) is a nonionic, block copolymer surfactant with hemorheologic, antithrombotic, and anti-adhesive properties. PP188 is being studied in phase III clinical trials in sickle cell disease and has been found to be well tolerated and has demonstrated benefit in ameliorating the effects of acute painful vasoocclusive crisis. The disposition of PP188 was studied in rats, dogs, and humans to establish a basis for understanding the safety parameters in support of clinical trials. PP188 was primarily distributed in extracellular water with little or no uptake by red blood cells, and had its highest concentrations in highly perfused tissues such as the kidney, liver, spleen, lymph nodes, and gastrointestinal tract. PP188 had no apparent effect on P450 isozymes in vitro. Metabolism was limited (<,5% of dose) with a higher molecular weight copolymer being the only other material detected in plasma or urine. Renal clearance was the controlling route of clearance for PP188 from the body. The 48-h intravenous infusion doses of PP188 were cleared in all species by approximately 1 week after the cessation of dose administration. PP188's disposition is a model for other nonionic block copolymers with similar physical and chemical properties. © 2002 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 91:1936,1947, 2002 [source] Direct parametric inference for the cumulative incidence functionJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2006Jong-Hyeon Jeong Summary., In survival data that are collected from phase III clinical trials on breast cancer, a patient may experience more than one event, including recurrence of the original cancer, new primary cancer and death. Radiation oncologists are often interested in comparing patterns of local or regional recurrences alone as first events to identify a subgroup of patients who need to be treated by radiation therapy after surgery. The cumulative incidence function provides estimates of the cumulative probability of locoregional recurrences in the presence of other competing events. A simple version of the Gompertz distribution is proposed to parameterize the cumulative incidence function directly. The model interpretation for the cumulative incidence function is more natural than it is with the usual cause-specific hazard parameterization. Maximum likelihood analysis is used to estimate simultaneously parametric models for cumulative incidence functions of all causes. The parametric cumulative incidence approach is applied to a data set from the National Surgical Adjuvant Breast and Bowel Project and compared with analyses that are based on parametric cause-specific hazard models and nonparametric cumulative incidence estimation. [source] Women with Pain due to Osteoarthritis: The Efficacy and Safety of a Once-Daily Formulation of TramadolPAIN MEDICINE, Issue 6 2009FRCP, Walter F. Kean MB ChB ABSTRACT Objective., This analysis assesses the efficacy and safety of treatment with a once-daily oral formulation of tramadol for up to 12 weeks compared with placebo in women with moderate-to-severe pain due to osteoarthritis of the knee. Design., Two parallel, placebo-controlled phase III clinical trials were analyzed; patients were randomized to a fixed dosage of Tramadol Contramid® once a day (OAD) 100, 200, and 300 mg daily, or placebo. Outcome Measures., The primary efficacy end points were the percentage difference from baseline of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) subscale scores for pain and physical function, and the patient global rating of pain relief after 12 weeks of maintenance therapy. Results., The analysis included 405 women receiving tramadol and 280 receiving placebo. At week 12, 179 of 204 women (87.7%) receiving tramadol rated their overall pain relief as effective or very effective compared with 134 of 177 (75.7%) receiving placebo. A time-weighted analysis revealed statistically significant improvements over placebo for all the WOMAC subscale scores across all three dosages. The percentage improvements from baseline of the WOMAC pain scores were significantly better than placebo for the 100-mg (58.8 ± 37.1%, P = 0.018) and 300-mg (58.9 ± 38.8%, P = 0.023) treatment arms; however, the 200-mg dosage was not significant (53.0 ± 38.5%, P = 0.175). The WOMAC physical function scores showed significant improvement for the 100 (56.9 ± 36.4%, P = 0.009), 200 (54.0 ± 33.8%, P = 0.034), and 300 mg (53.4 ± 41.4%, P = 0.043) daily dosages. Conclusion., For moderate-to-severe pain due to osteoarthritis of the knee, women experience significant analgesia and improvement of physical function over time with treatment with Tramadol Contramid® OAD. [source] From history to reality: sodium glucose co-transporter 2 inhibitors , a novel therapy for type 2 diabetes mellitusPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 7 2010S Nair MRCP(UK) Abstract The human kidney has a key role in the regulation of blood glucose predominantly by reabsorption of glucose from the glomerular filtrate via sodium glucose co-transporter 2 (SGLT-2) channels. These are expressed in the proximal renal tubules and are blocked by SGLT-2 inhibitors, which are novel pharmacological agents currently in development. Specific SGLT-2 inhibition results in significant increases in renal glucose excretion causing a net calorie loss and consequent weight loss, coupled with a lowering of blood glucose due to removal of glucose from the circulation. The main side effect of SGLT-2 inhibitors appears to be an increase in genital infections, although concerns remain about the potential adverse effects of dehydration and electrolyte imbalance. Dapagliflozin is the SGLT-2 inhibitor that is the furthest along in development, and is currently in phase III clinical trials. In this review article we consider the role of the kidney in glucose homeostasis in normal and diabetic subjects. We also review the history and concept of SGLT-2 inhibition, and discuss the future potential clinical utility of this promising new class of drugs. Copyright © 2010 John Wiley & Sons. [source] Quality assurance within the scope of Good Clinical Practice (GCP),what is the cost of GCP-related activities?QUALITY ASSURANCE JOURNAL, Issue 1 2009A survey within the Swedish Association of the Pharmaceutical Industry (LIF)'s members Abstract The bureaucracy that the Good Clinical Practice (GCP) system generates, due to industry over-interpretation of documentation requirements, clinical monitoring, data verifications etc. is substantial. The aim of this study was to estimate the percentage cost of all such GCP-related activities within phase III clinical trials performed in Sweden in 2005. Method: An electronic questionnaire on ICH GCP-activities and their related costs was sent to 47 of the 60 member companies of the Swedish Association of the Pharmaceutical Industry (LIF). Results: The number of respondents was 29, giving a response rate of 62% and covering 97% (n=250) of phase III trials performed in Sweden in 2005. Approximately 50% of the total budget for a phase III study was reported to be GCP-related. 50% of the GCP-related cost was related to Source Data Verification (SDV). A vast majority (71%) of respondents did not support the notion that these GCP-related activities increase the scientific reliability of clinical trials. Copyright © 2009 John Wiley & Sons, Ltd. [source] Better Regulation of Industry-Sponsored Clinical Trials Is Long OverdueTHE JOURNAL OF LAW, MEDICINE & ETHICS, Issue 3 2009Matthew Wynia Regulating clinical trials for testing new drugs is fraught with risk. Misregulation can slow development of innovative and useful new drugs, but in other ways misregulation can foster trials that are inefficient and unethical, driven by commercial rather than scientific ends, and that can harm patients. In this paper, we argue not for more but for better regulation, based on the goal of rapidly producing innovative and safe products that represent significant advances in medical care. Data on industry-funded, late-stage clinical trials demonstrate an urgent need for dramatic changes in how these trials are designed, conducted, and analyzed. On the one hand, current patent rules can dissuade development of innovative new products with smaller markets and press trial designers to create positive results too rapidly. But at the same time, numerous studies show that when the pharmaceutical industry sponsors clinical trials, the results are systematically biased in favor of the sponsor's product, often to the detriment of patients and the public. The reasons for this bias are both complex and unavoidable, and the ways in which clinical trial design, conduct, and reporting can be inappropriately influenced are so varied and nuanced, that efforts to manage this conflict of interest and prevent harms are inevitably unsuccessful. Instead, we conclude such conflict should be avoided and a strong firewall should exist between drug developers and the final stages of clinical testing in humans. All financial support for phase III clinical trials should pass through a public-private partnership organization , perhaps tied to a broader clinical effectiveness research enterprise , which would be charged with designing, funding, and monitoring late-stage human clinical trials of new pharmaceutical products. [source] ORIGINAL RESEARCH,BASIC SCIENCE: Acute and Repeated Flibanserin Administration in Female Rats Modulates Monoamines Differentially Across Brain Areas: A Microdialysis StudyTHE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010Kelly A. Allers PhD ABSTRACT Introduction., Hypoactive sexual desire disorder (HSDD) is defined as persistent lack of sexual fantasies or desire marked by distress. With a prevalence of 10% it is the most common form of female sexual dysfunction. Recently, the serotonin-1A (5-HT1A) receptor agonist and the serotonin-2A (5-HT2A) receptor antagonist flibanserin were shown to be safe and efficacious in premenopausal women suffering from HSDD in phase III clinical trials. Aim., The current study aims to assess the effect of flibanserin on neurotransmitters serotonin (5-HT), norepinephrine (NE), dopamine (DA), glutamate, and ,-aminobutyric acid (GABA) in brain areas associated with sexual behavior. Methods., Flibanserin was administered to female Wistar rats (280,350 g). Microdialysis probes were stereotactically inserted into the mPFC, NAC, or MPOA, under isoflurane anesthesia. The extracellular levels of neurotransmitters were assessed in freely moving animals, 24 hours after the surgery. Main Outcome Measures., Dialysate levels of DA, NE, and serotonin from medial prefrontal cortex (mPFC), nucleus accumbens (NAC), and hypothalamic medial preoptic area (MPOA) from female rats. Results., Acute flibanserin administration decreased 5-HT and increased NE levels in all tested areas. DA was increased in mPFC and MPOA, but not in the NAC. Basal levels of NE in mPFC and NAC and of DA in mPFC were increased upon repeated flibanserin administration, when compared to vehicle-treated animals. The basal levels of 5-HT were not altered by repeated flibanserin administration, but basal DA and NE levels were increased in the mPFC. Glutamate and GABA levels remained unchanged following either repeated or acute flibanserin treatment. Conclusions., Systemic administration of flibanserin to female rats differentially affects the monoamine systems of the brain. This may be the mechanistic underpinning of flibanserin's therapeutic efficacy in HSDD, as sexual behavior is controlled by an intricate interplay between stimulatory (catecholaminergic) and inhibitory (serotonergic) systems. Allers KA, Dremencov E, Ceci A, Flik G, Ferger B, Cremers TIFH, Ittrich C, and Sommer B. Acute and repeated flibanserin administration in female rats modulates monoamines differentially across brain areas: A microdialysis study. J Sex Med 2010;7:1757,1767. [source] Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical TrialsARCHIV DER PHARMAZIE, Issue 9 2010Adeeb Shehzad Abstract Curcumin (diferuloylmethane), a derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Abundant sources provide interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. The pleiotropic role of this dietary compound includes the inhibition of several cell signaling pathways at multiple levels, such as transcription factors (NF-,B and AP-1), enzymes (COX-2, MMPs), cell cycle arrest (cyclin D1), proliferation (EGFR and Akt), survival pathways (,-catenin and adhesion molecules), and TNF. Curcumin up-regulates caspase family proteins and down-regulates anti-apoptotic genes (Bcl-2 and Bcl-XL). In addition, cDNA microarrays analysis adds a new dimension for molecular responses of cancer cells to curcumin at the genomic level. Although, curcumin's poor absorption and low systemic bioavailability limits the access of adequate concentrations for pharmacological effects in certain tissues, active levels in the gastrointestinal tract have been found in animal and human pharmacokinetic studies. Currently, sufficient data has been shown to advocate phase II and phase III clinical trials of curcumin for a variety of cancer conditions including multiple myeloma, pancreatic, and colon cancer. [source] Monoclonal antibodies as effective therapeutic agents for solid tumorsCANCER SCIENCE, Issue 8 2004Yuji Hinoda Monoclonal antibodies (mAbs) against growth factors or their receptors have been revealed to be effective therapeutic agents for solid tumors. Trastuzumab (humanized anti-HER2 mAb) is the first mAb approved for the treatment of a solid tumor, metastatic breast cancer. Large-scale phase III clinical trials are now ongoing to further evaluate the additive effects on chemotherapy and the efficacy as a maintenance monotherapy. Another anti-HER2 mAb CH401 that we developed also seems to have good potential. This chimeric mAb completely suppressed the growth of established human tumor xenografts in SCID mice after a single injection. Furthermore, CH401 characteristically showed much stronger induction of apoptosis in HER2-overexpressing gastric cancer cells compared to trastuzumab. Additional targets now being intensively evaluated are epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF). Both cetuximab (chimeric anti-EGFR mAb) and bevacizumab (humanized anti-VEGF mAb) have recently been shown to be of clinical value for metastatic colorectal cancer. Anti-idiotype mAbs are unique as active immunotherapeutic agents, and survival benefits have been observed in clinical trials for solid tumors. [source] | |||||||||||||||||||||||||