Biomedical subjects

Gillian M Keating

Publications and source records attributed to Gillian M Keating.

At least 19 recordsLinked to original sources

PubMed2007

Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome and type 2 diabetes mellitus.

Fenofibrate is a fibric acid derivative indicated for use in the treatment of primary hypercholesterolaemia, mixed dyslipidaemia and hypertriglyceridaemia in adults who have not responded to nonpharmacological measures. Its lipid-modifying effects are mediated by activation of peroxisome proliferator-activated receptor-alpha. Fenofibrate also has nonlipid (i.e. pleiotropic) effects (e.g. it reduces fibrinogen, C-reactive protein and uric acid levels and improves flow-mediated dilatation). Fenofibrate improves lipid levels (in particular triglyceride [TG] and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with primary dyslipidaemia. Its lipid-lowering profile means that fenofibrate is particularly well suited for use in atherogenic dyslipidaemia (characterised by high TG levels, low HDL-C levels and small, dense low-density lipoprotein [LDL] particles), which is commonly seen in patients with the metabolic syndrome and type 2 diabetes mellitus. Indeed, fenofibrate improves the components of atherogenic dyslipidaemia in patients with these conditions, including a shift from small, dense LDL particles to larger, more buoyant LDL particles. Greater improvements in lipid levels are seen when fenofibrate is administered in combination with an HMG-CoA reductase inhibitor (statin) or in combination with ezetimibe, compared with monotherapy with these agents. In the DAIS study, fenofibrate significantly slowed the angiographic progression of focal coronary atherosclerosis in patients with type 2 diabetes. In terms of clinical outcomes, although no significant reduction in the risk of coronary events was seen with fenofibrate in the FIELD trial in patients with type 2 diabetes, treatment was associated with a significantly reduced risk of total cardiovascular disease (CVD) events, primarily through the prevention of non-fatal myocardial infarction and coronary revascularisation. Subgroup analyses revealed significant reductions in total CVD events and coronary heart disease events in patients with no previous CVD, suggesting a potential role for primary prevention with fenofibrate in patients with early type 2 diabetes. Improvements were also seen in microvascular outcomes with fenofibrate in the FIELD trial. Fenofibrate is generally well tolerated, both as monotherapy and when administered in combination with a statin. Combination therapy with fenofibrate plus a statin appears to be associated with a low risk of rhabdomyolysis; no cases of rhabdomyolysis were reported in patients receiving such therapy in the FIELD trial. Thus, fenofibrate is a valuable lipid-lowering agent, particularly in patients with atherogenic dyslipidaemia.

Diabetes Mellitus, Type 2↗

PubMed2006

Travoprost/timolol.

Travoprost 0.004%/timolol 0.5% fixed combination (travoprost/timolol) is a once-daily eyedrops solution comprising the prostaglandin F(2alpha) analogue travoprost and the beta-adrenoceptor antagonist timolol. It is indicated for the treatment of patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-adrenoceptor antagonists or prostaglandin analogues. Once-daily travoprost/timolol had generally similar efficacy to travoprost plus timolol and was more effective than travoprost or timolol monotherapy in reducing intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension in randomised, well designed studies. Both travoprost/timolol and latanoprost plus timolol maintained IOP control, and travoprost/timolol was shown to be noninferior to latanoprost/timolol in randomised, well designed studies. Travoprost/timolol was generally well tolerated, with a tolerability profile similar to those of travoprost plus timolol, travoprost or timolol monotherapy and latanoprost plus timolol. The majority of adverse events, such as ocular hyperaemia, were mild and resolved with or without treatment.

Cloprostenol↗

PubMed2006

Pioglitazone: a review of its use in type 2 diabetes mellitus.

Pioglitazone is an antihyperglycaemic agent that, in the presence of insulin resistance, increases hepatic and peripheral insulin sensitivity, thereby inhibiting hepatic gluconeogenesis and increasing peripheral and splanchnic glucose uptake. Pioglitazone is generally well tolerated, weight gain and oedema are the most common emergent adverse events, and there are no known drug interactions between pioglitazone and other drugs. In clinical trials in patients with type 2 diabetes mellitus, pioglitazone as monotherapy, or in combination with metformin, repaglinide, insulin or a sulphonylurea, induced both long- and short-term improvements in glycaemic control and serum lipid profiles. Pioglitazone was also effective in reducing some measures of cardiovascular risk and arteriosclerosis. Pioglitazone thus offers an effective treatment option for the management of patients with type 2 diabetes.

Blood Glucose↗

PubMed2006

Anagrelide: a review of its use in the management of essential thrombocythaemia.

Anagrelide (Agrylin, Xagrid) is an oral imidazoquinazoline agent which is indicated in Europe for the reduction of elevated platelet counts in at-risk patients with essential thrombocythaemia who are intolerant of or refractory to their current therapy, and in the US for the reduction of elevated platelet counts and the amelioration of thrombohaemorrhagic events in patients with thrombocythaemia associated with myeloproliferative disorders. Anagrelide is well established as an effective platelet-lowering agent in most patients with essential thrombocythaemia, including both treatment-naive patients and those refractory to other cytoreductive therapy. Results of the only randomised trial to date (the Primary Thrombocythaemia 1 [PT1] study) indicated that the composite primary endpoint (arterial or venous thrombosis, serious haemorrhage or death from vascular causes) occurred more often in recipients of anagrelide plus aspirin than in those receiving hydroxycarbamide (hydroxyurea) plus aspirin. This trial also indicated that the incidence of the secondary endpoints transient ischaemic attack and gastrointestinal bleeding favoured hydroxycarbamide plus aspirin, while the incidence of venous thrombosis favoured anagrelide plus aspirin. There were no differences between the groups in the incidence of secondary endpoints myocardial infarction, stroke, unstable angina, pulmonary embolism, hepatic-vein thrombosis, other serious haemorrhage or related deaths. The design of the PT1 study has been queried with respect to the heterogeneous nature of the study population (possible inclusion of patients with early myelofibrotic disease) and the concomitant use of aspirin (interaction with anagrelide causing increased bleeding events). Further data are therefore required before the role of anagrelide in essential thrombocythaemia can be finalized. In the meantime, when considering treatment options for patients with this disorder, anagrelide's positive effects on platelet function, lack of mutagenicity and lack of association with leukaemia or angiogenesis must be balanced against its comparative expense and positive inotropic effects. Thus, the role of anagrelide in the management of high-risk patients with essential thrombocythaemia will ultimately depend on individual patient assessment and future clarification of the potential leukaemogenicity of hydroxycarbamide.

Blood Platelets↗

PubMed2006

Tramadol sustained-release capsules.

Tramadol is a synthetic, centrally acting analgesic. A sustained-release (SR) capsule formulation of tramadol gradually releases active drug, allowing for twice-daily dosing. Compared with tramadol SR tablets, tramadol SR capsules produced a smoother plasma concentration profile, with more gradual absorption and lower peak concentrations. There was less intra- and intersubject variability in tramadol plasma concentrations with SR capsules versus SR. Tramadol SR capsules had identical bioavailability to tramadol immediate-release (IR) capsules with lower peak concentrations and less fluctuation in plasma concentrations. Tramadol SR 100 mg capsules administered twice daily had equivalent efficacy to tramadol IR 50 mg capsules administered four times daily in the treatment of moderate to severe chronic low back pain in a well designed study. Patients receiving tramadol SR capsules were significantly less likely than those receiving tramadol IR capsules to report nausea. Starting treatment with tramadol SR capsules at a dosage of 50 mg twice daily with subsequent dose escalation resulted in improved tolerability in patients with moderate to severe chronic pain. The lowest tramadol SR capsule dosage of 50 mg twice daily (administered to 35% of patients with moderate to severe non-oncological pain) significantly improved pain intensity and frequency in 83.4% and 70.4% of patients, respectively, in a postmarketing observational study evaluating tramadol SR capsules 50-200 mg twice daily (n = 3888).

Analgesics, Opioid↗

PubMed2006

Remifentanil : a review of its analgesic and sedative use in the intensive care unit.

Remifentanil (Ultiva), a 4-anilidopiperidine derivative of fentanyl, is an ultra-short-acting micro-opioid receptor agonist indicated to provide analgesia and sedation in mechanically ventilated intensive care unit (ICU) patients.Analgesia-based sedation with remifentanil is a useful option for mechanically ventilated patients in the ICU setting. Its unique properties (e.g. organ-independent metabolism, lack of accumulation, rapid offset of action) set it apart from other opioid agents. Remifentanil is at least as effective as comparator opioids such as fentanyl, morphine and sufentanil in providing pain relief and sedation in mechanically ventilated ICU patients. Moreover, it allows fast and predictable extubation, as well as being associated with a shorter duration of mechanical ventilation and quicker ICU discharge than comparators in some studies. In addition, remifentanil is generally well tolerated in this patient population. Thus, remifentanil is a welcome addition to the currently available pharmacological agents employed in the management of mechanically ventilated ICU patients.

Age Factors↗

PubMed2006

Moxonidine: a review of its use in essential hypertension.

Moxonidine (Physiotens, Moxon, Cynt) is an orally administered imidazoline compound with selective agonist activity at imidazoline I1 receptors and only minor activity at alpha2-adrenoceptors. Moxonidine acts centrally to reduce peripheral sympathetic activity, thus decreasing peripheral vascular resistance. In patients with mild to moderate hypertension, moxonidine reduces blood pressure (BP) as effectively as most first-line antihypertensives when used as monotherapy and is also an effective adjunctive therapy in combination with other antihypertensive agents. It improves the metabolic profile in patients with hypertension and diabetes mellitus or impaired glucose tolerance, is well tolerated, has a low potential for drug interactions and may be administered once daily in most patients. Thus, moxonidine is a good option in the treatment of patients with mild to moderate hypertension, particularly as adjunctive therapy in patients with the metabolic syndrome.

Animals↗

PubMed2006

Dexmethylphenidate extended release: in attention-deficit hyperactivity disorder.

Dexmethylphenidate extended release (XR) is an orally administered, bimodal release, capsule formulation of the active d-enantiomer of methylphenidate (MPH), which inhibits dopamine and norepinephrine (noradrenaline) reuptake to increase their concentration in the extraneuronal space. A single dose of dexmethylphenidate XR mimics the pharmacokinetic profile of two doses of dexmethylphenidate immediate-release formulation administered 4 hours apart, albeit with less fluctuation in plasma concentration. Once-daily dexmethylphenidate XR was more effective than placebo in reducing attention-deficit hyperactivity disorder (ADHD) symptom scores in children, adolescents and adults with ADHD in four randomised, double-blind, placebo-controlled trials of up to 7 weeks' duration. In crossover trials in children (aged 6-12 years), dexmethylphenidate XR 20 mg/day reduced mean ADHD symptom scores 1 hour after administration (by 43% in one trial) and was significantly better than placebo for up to 12 hours. Dexmethylphenidate XR 5-30 mg/day reduced mean ADHD symptom scores by 49%, while scores declined by 16% with placebo in a 7-week trial in children and adolescents (aged 6-17 years). Dexmethylphenidate XR 20, 30 or 40 mg/day reduced ADHD symptom scores by 36-46% versus a 21% reduction with placebo in a 5-week trial in adults (aged 18-60 years). Dexmethylphenidate XR was generally well tolerated in children, adolescents and adults with ADHD, with an adverse-event profile typical of MPH.

Adolescent↗

PubMed2006

Gadofosveset.

Gadofosveset is the first gadolinium-based magnetic resonance (MR) imaging agent designed to image the blood pool. At clinically relevant concentrations, gadofosveset is highly bound to human serum albumin, which has the effect of increasing its signal-enhancing properties above that of non-protein bound imaging agents, as well as increasing its plasma half-life, allowing for increased imaging times. The use of gadofosveset-enhanced MR angiography was compared with non-enhanced MR angiography in four open-label, multicentre studies in adults with known or suspected arterial disease. Significant improvements in the accuracy and specificity of diagnosis were seen with gadofosveset in patients with aortoiliac disease in two studies. Sensitivity was also improved, with all three readers in one study, and two of three readers in the other study, showing significant improvements with gadofosveset use. Significant improvements in sensitivity, specificity, and accuracy were also seen with gadofosveset in a renal artery disease study. Specificity was significantly improved in patients with pedal artery disease across all readers, with accuracy and sensitivity significantly improved in two of three and one of three readers. Gadofosveset was generally well tolerated in clinical trials, with most adverse events being mild or moderate in severity.

Adult↗

PubMed2006

Sumatriptan fast-disintegrating/rapid-release tablets.

Sumatriptan is a serotonin 5-HT(1B/1D) receptor agonist that is used for the acute treatment of migraine attacks. A new fast-disintegrating/rapid-release sumatriptan tablet (sumatriptan FDT/RRT) has been developed with the goal of speeding absorption and onset of effect compared with standard sumatriptan tablets. Bioequivalence of sumatriptan FDT/RRT tablets to standard sumatriptan tablets was established in healthy volunteers. Initial data suggest that sumatriptan FDT/RRT tablets may disintegrate faster and get emptied from the stomach faster than standard sumatriptan tablets. In a randomised, double-blind, multicentre, early intervention trial in adults with mild migraine, significantly more sumatriptan FDT/RRT 50 and 100mg recipients than placebo recipients were pain free or migraine free 2 hours after receiving study medication. Compared with placebo, pain relief was significantly greater with sumatriptan FDT/RRT 100mg at 25 and 17 minutes following administration, and with sumatriptan FDT/RRT 50mg at 50 and 30 minutes following administration, in two randomised, double-blind, multicentre trials in adults with moderate to severe migraine. Sumatriptan FDT/RRT tablets were generally well tolerated; the tolerability profile was similar to that reported for standard sumatriptan tablets in other studies.

Adult↗

PubMed2006

Albumin-bound Paclitaxel: in metastatic breast cancer.

A new formulation of paclitaxel, 130-nanometre albumin-bound paclitaxel (nab-paclitaxel), solubilises hydrophobic paclitaxel and may increase paclitaxel delivery to tumour cells. Intravenous nab-paclitaxel 260 mg/m(2) had a higher maximum whole-blood concentration, shorter time to peak concentration, larger distribution volume and greater clearance than a 175 mg/m(2) dose of a conventional polyoxyethylated castor oil (Cremophor EL) solublised paclitaxel (CrEL-paclitaxel). The reconciled target-lesion response rate was significantly higher in patients receiving intravenous nab-paclitaxel 260 mg/m(2) once every 3 weeks than in those receiving CrEL-paclitaxel 175 mg/m(2) once every 3 weeks (21.5% vs 11.1%) in a randomised, nonblind, phase III trial in 454 patients with metastatic breast cancer. The objective response rate (ORR) was also significantly greater in nab-paclitaxel than in CrEL-paclitaxel recipients (33% vs 19%). In noncomparative phase II trials, ORRs of 48% and 51% were observed in patients receiving nab-paclitaxel 175 or 300 mg/m(2) once every 3 weeks. nab-Paclitaxel 260 mg/m(2) caused less grade 4 neutropenia than CrEL-paclitaxel 175 mg/m(2). The incidence of grade 3 sensory neuropathy was higher in nab-paclitaxel recipients, reflecting the higher dosage of nab-paclitaxel, and improved with treatment interruption. Despite the absence of corticosteroid and antihistamine premedication, no severe hypersensitivity reactions were reported.

Albumins↗

PubMed2006

Delapril/manidipine.

Delapril/manidipine 30 mg/10 mg is a new oral, once-daily, fixed combination of an ACE inhibitor and a dihydropyridine calcium-channel antagonist for the treatment of essential hypertension. In a dose-finding study in 400 patients with mild to moderate hypertension, delapril/manidipine 30mg/10mg once daily produced the greatest reduction in blood pressure (BP) of the combinations tested. Delapril/manidipine 30mg/10mg once daily for 6 weeks reduced systolic BP (SBP)/diastolic BP (DBP) by 15/13mm Hg. In nonresponders to monotherapy with delapril (n = 155) or manidipine (n = 152), delapril/manidipine 30mg/10mg once daily for 12 weeks reduced mean SBP/DBP by 16/11mm Hg and 16/10mm Hg, respectively. Delapril/manidipine 30mg/10mg once daily for 12 weeks in patients with mild to moderate hypertension (n = 131) demonstrated significantly greater antihypertensive efficacy than monotherapy with manidipine 10mg once daily (n = 134) or delapril 15mg twice daily (n = 136). Mean SBP/DBP reductions from baseline were 19/14, 15/11 and 14/10mm Hg, respectively. After 50 weeks of therapy with delapril/manidipine 30mg/10mg once daily, mean SBP/DBP was reduced by 22/14mm Hg in patients with mild to moderate hypertension (n = 309). Delapril/manidipine 30mg/10mg once daily was generally well tolerated. The incidence and nature of adverse events were similar to those observed in recipients of monotherapy with the individual agents. Combination therapy was associated with less ankle oedema than manidipine monotherapy.

Administration, Oral↗

PubMed2006

Darbepoetin alfa: a review of its use in the treatment of anaemia in patients with cancer receiving chemotherapy.

Darbepoetin alfa (Aranesp) is an analogue of recombinant human erythropoietin (rHuEPO) produced using recombinant DNA technology. The high number of sialic acid moieties in darbepoetin alfa results in a prolonged half-life and enhanced in vivo biological activity compared with rHuEPO (as demonstrated in animal studies) and permits a reduction in the frequency of administration. Subcutaneous darbepoetin alfa 2.25 microg/kg once weekly or 500 microg once every 3 weeks (with a provision for dose adjustments) is an effective and well tolerated erythropoietic agent in anaemic patients with cancer receiving chemotherapy. In randomised, controlled clinical trials, the drug increased haemoglobin levels and reduced the need for blood transfusions in patients with various types of nonmyeloid malignancies and also ameliorated anaemia-related fatigue, thereby improving their health-related quality of life (HR-QOL) scores. The once-every-3-weeks dosage regimen provides further convenience by offering the possibility of synchronising its administration with most chemotherapy regimens. Direct comparisons between approved dosages of darbepoetin alfa and other erythropoietic agents have not been conducted. Such comparisons would be very helpful in formulating definitive conclusions about their relative efficacy and cost effectiveness. Darbepoetin alfa provides an effective and well tolerated treatment option for the treatment of anaemia in patients with cancer receiving chemotherapy.

Anemia↗

PubMed2006

Eletriptan: a review of its use in the acute treatment of migraine.

Eletriptan (Relpax) is an orally administered, lipophilic, highly selective serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute treatment of moderate to severe migraine attacks in adults. It has a rapid onset of action and demonstrates superiority over placebo as early as 30 minutes after the administration of a single 40 or 80 mg oral dose. The efficacy of eletriptan 20 mg was similar to that of sumatriptan 100 mg, while eletriptan 40 and 80 mg displayed greater efficacy than sumatriptan 50 or 100 mg for most endpoints. Eletriptan 40 mg was generally superior to naratriptan 2.5 mg and equivalent to almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg, while eletriptan 80 mg was superior to zolmitriptan 2.5 mg for most efficacy parameters. Eletriptan 40 and 80 mg were consistently superior to ergotamine/caffeine. Eletriptan is generally well tolerated, reduces time lost from normal activities, improves patients' health-related quality of life and appears to be at least as, if not more, cost effective than sumatriptan. Eletriptan is therefore a useful addition to the triptan family and a first-line treatment option in the acute management of migraine attacks.

Animals↗

PubMed2006

Beclometasone dipropionate/formoterol: in an HFA-propelled pressurised metered-dose inhaler.

A hydrofluoroalkane (HFA)-propelled pressurised metered-dose inhaler (pMDI) has been developed (using Modulite technology) for a new fixed combination of beclometasone dipropionate/formoterol fumarate (BDP/formoterol) 100 microg/6 microg. Each actuation of the BDP/formoterol HFA pMDI 100 microg/6 microg delivers 86.4 microg of BDP and 5 microg of formoterol. BDP/formoterol HFA pMDI was associated with significantly higher morning peak expiratory flow (PEF) values than BDP administered alone via a chlorofluorocarbon (CFC) pMDI (including when BDP was administered at a higher dosage) in well designed trials in adults with mild to moderate or moderate to severe asthma. In terms of morning PEF values, BDP/formoterol HFA pMDI was noninferior to BDP plus formoterol administered via separate inhalers in well designed trials in adults with moderate to severe asthma. BDP/formoterol HFA pMDI was noninferior to fixed-combination budesonide/formoterol (the daily dosage of BDP was half that of budesonide) in terms of lung function, asthma symptoms and use of rescue medications in adults with moderate to severe asthma. BDP/formoterol HFA pMDI was also noninferior to, and had a faster onset of bronchodilation than, fixed-combination fluticasone propionate/salmeterol. BDP/formoterol 200 microg/12 microg per day or 400 microg/24 microg per day administered by the HFA pMDI was generally well tolerated. Moreover, a single high dose of BDP/formoterol (1000 microg/60 microg) was generally well tolerated in patients with asthma.

Administration, Inhalation↗

PubMed2006

Memantine: a review of its use in Alzheimer's disease.

Memantine (Ebixa, Axura, Namenda, Akatinol) is a moderate-affinity, uncompetitive, voltage-dependent, NMDA-receptor antagonist with fast on/off kinetics that inhibits excessive calcium influx induced by chronic overstimulation of the NMDA receptor. Memantine is approved in the US and the EU for the treatment of patients with moderate to severe dementia of the Alzheimer's type. In well designed clinical trials, oral memantine, as monotherapy or in addition to a stable dose of acetylcholinesterase inhibitors, was well tolerated during the treatment of mild to severe Alzheimer's disease for up to 52 weeks. Memantine generally modified the progressive symptomatic decline in global status, cognition, function and behaviour exhibited by patients with moderate to severe Alzheimer's disease in four 12- to 28-week trials. In patients with mild to moderate Alzheimer's disease, data from three 24-week trials are equivocal, although meta-analyses indicate beneficial effects on global status and cognition. Memantine is an effective pharmacotherapeutic agent, and currently the only approved option, for the treatment of moderate to severe Alzheimer's disease.

Alzheimer Disease↗

PubMed2006

Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indications.

Nicardipine is a water soluble calcium channel antagonist, with predominantly vasodilatory actions. Intravenous (IV) nicardipine (Cardene IV), which demonstrates a relatively rapid onset/offset of action, is used in situations requiring the rapid control of blood pressure (BP). IV nicardipine was as effective as IV nitroprusside in the short-term reduction of BP in patients with severe or postoperative hypertension. A potential role for IV nicardipine in the intraoperative acute control of BP in patients undergoing various surgical procedures (including cardiovascular, neurovascular and abdominal surgery), and in the deliberate induction of reduced BP in surgical procedures in which haemostasis may be difficult (e.g. surgery involving the hip or spine) was demonstrated in preliminary studies. Preliminary studies also indicated the ability of a bolus dose of IV nicardipine to attenuate the hypertensive response, but not the increase in tachycardia, after laryngoscopy and tracheal intubation in anaesthetised patients. In large, well designed studies, IV nicardipine prevented cerebral vasospasm in patients with recent aneurysmal subarachnoid haemorrhage; however, overall clinical outcomes at 3 months were similar to those in patients who received standard management. Small preliminary studies have investigated the use of IV nicardipine in a variety of other settings, including acute intracerebral haemorrhage, acute ischaemic stroke, pre-eclampsia, acute aortic dissection, premature labour and electroconvulsive therapy.In conclusion, the efficacy of IV nicardipine in the short-term treatment of hypertension in settings for which oral therapy is not feasible or not desirable is well established. The ability to titrate IV nicardipine to the tolerance levels of individual patients makes this agent an attractive option, especially in critically ill patients or those undergoing surgery. Potential exists for further investigation of the use of this agent in clinical settings where a vasodilatory agent with minimal inotropic effects is appropriate.

Antihypertensive Agents↗

PubMed2006

Sunitinib.

Sunitinib and its active metabolite (SU012662) are selective inhibitors of multiple receptor tyrosine kinases associated with tumour growth and angiogenesis. The clinical efficacy of oral sunitinib has been demonstrated in patients with advanced gastrointestinal stromal tumours (GIST). In a phase III, randomised, double-blind, placebo-controlled, multicentre trial in patients with metastatic and/or unresectable GIST following unsuccessful imatinib therapy, the median time to tumour progression and median progression-free survival time were > or =4-fold longer in patients receiving sunitinib 50 mg/day than in those receiving placebo, in 6-week cycles consisting of 4 weeks of treatment followed by a 2-week rest period. Sunitinib also exhibited antitumour activity in patients with advanced renal cell carcinoma (RCC) following unsuccessful cytokine therapy. In two multicentre, single-arm, phase II clinical trials in patients with cytokine-refractory metastatic RCC, partial responses were reported in 40% and 43% of patients receiving sunitinib 50 mg/day for 4 weeks followed by 2 weeks without treatment in 6-week cycles; 27% and 22% of patients achieved stable disease for > or =3 months. Sunitinib was more effective than interferon-alpha as a first-line therapy in patients with metastatic RCC. In a large, well designed, phase III trial in previously untreated patients, progression-free survival was significantly longer in patients receiving sunitinib 50 mg/day in 6-week cycles (4 weeks of treatment followed by a 2-week rest period) compared with those receiving interferon-alpha 9MU three times weekly (47.3 vs 24.9 weeks). In general, sunitinib was well tolerated in patients with GIST and RCC, with adverse events usually being of mild or moderate severity.

Antineoplastic Agents↗