Year Of Combination Therapy Research Articles

Acquired lymphangiectasis following surgery and radiotherapy of breast cancer.

Acquired lymphangiectasia (AL) is a significant and rare complication of surgery and radiotherapy. We report lymphangiectasia in a 40-year-old woman who had undergone radical mastectomy and radiotherapy. After 4 years of combined therapy, she developed multiple vesicles and bullae. Skin biopsy confirmed the diagnosis of lymphangiectasia. The case is unique as it is not associated with lymphedema, which is a usual accompaniment of lymphangiectasia following surgery and radiotherapy. AL is usually asymptomatic, but trauma may cause recurrent cellulitis. Treatment modalities include electrodessication, surgical excision, sclerotherapy and carbon dioxide laser ablation.

Outcome of Lamivudine-Resistant Chronic Hepatitis B after up to 5 Years of Combination Therapy with Adefovir

There is a paucity of data on the long-term efficacy of combination lamivudine and adefovir therapy in patients with lamivudine-resistant chronic hepatitis B. We determined the cumulative virological, serological and biochemical outcomes of 165 lamivudine-resistant chronic hepatitis B patients on lamivudine and adefovir for up to 5 years. Resistance profiles using a line probe assay were determined among patients with detectable viraemia. The significance of different baseline and on-treatment virological parameters was analysed. The median age and duration of follow-up were 45.1 years and 37.1 months, respectively. The cumulative rates of HBV DNA undetectability (<20 IU/ml), alanine aminotransferase normalization and hepatitis B e antigen seroconversion up to 5 years were 74.0%, 95.1% and 44.4%, respectively. One patient achieved hepatitis B surface antigen seroclearance. The 5-year cumulative resistance rate to adefovir was 10.2%. Among different baseline and on-treatment virological parameters, week 24 HBV DNA<200 IU/ml was associated with an increased chance of long-term virological suppression (P<0.001, OR 13.89, 95% CI 3.90, 49.46). Primary non-response and high baseline viral titres were not useful in predicting long-term virological outcomes. The 5-year cumulative rate of serum creatinine elevation >0.5 mg/dl was 4.1%. Combination lamivudine and adefovir therapy for up to 5 years achieved modest rates of virological suppression, but resistance developed in only 10.2% of patients. Week 24 HBV DNA<200 IU/ml was predictive of favourable long-term virological outcomes and could be used to assist treatment decisions on continuing lamivudine and adefovir or switching to more potent therapy.

Hepatitis B e antigen predicts delayed reduction of HBV DNA without viral breakthrough with adefovir dipivoxil and lamivudine: A 5‐year study of patients with hepatitis B with lamivudine resistance

To clarify the factors associated with delayed reduction of HBV DNA during combination treatment with adefovir dipivoxil (ADV) and lamivudine (LAM) for patients with LAM-resistant hepatitis B virus (HBV), factors including patient characteristics, viral mutations, and drug metabolism were investigated during a 5-year observation period. Delayed reduction of HBV DNA was defined as delayed viral response of detectable HBV DNA after 3 years of combination therapy. Of 67 consecutive patients, 47 attained undetectable HBV DNA after 3 years of combination therapy, and the mean therapeutic duration was 5 years (range: 3.0-8.4 years). The patients with delayed viral response had high levels of HBV DNA and HBe antigen, while those with negative or low levels of HBe antigen were also negative for HBV DNA, even if they had high levels of HBV DNA. In the multivariate analysis with the proportional hazards model, a high baseline level of HBe antigen was negatively associated with viral decline to an undetectable level (P = 0.013). A higher baseline of HBe antigen corresponded to a lower annual decline in HBV DNA (R = -0.38, P = 0.004). No patients showed ADV-resistant mutations in the HBV reverse transcriptase region. Trough concentrations of LAM and ADV showed no clear associations with viral response. HBe antigen levels at the initiation of therapy, and reductions in these levels during therapy are predictive of the therapeutic response to combination therapy with ADV and LAM for patients with LAM-resistant HBV.

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α-Blocker Monotherapy and α-Blocker Plus 5-Alpha-Reductase Inhibitor Combination Treatment in Benign Prostatic Hyperplasia; 10 Years' Long-Term Results

PurposeWe compared the effects of alpha-adrenergic receptor blocker (α-blocker) monotherapy with those of combination therapy with α-blocker and 5-alpha-reductase inhibitor (5-ARI) on benign prostatic hyperplasia (BPH) progression for over 10 years.Materials and MethodsA total of 620 patients with BPH who received α-blocker monotherapy (α-blocker group, n=368) or combination therapy (combination group, n=252) as their initial treatment were enrolled from January 1989 to June 2000. The incidences of acute urinary retention (AUR) and BPH-related surgery were compared between the two groups. Incidences stratified by follow-up period, prostate-specific antigen (PSA), and prostate volume (PV) were compared between the two groups.ResultsThe incidence of AUR was 13.6% (50/368) in the α-blocker group and 2.8% (7/252) in the combination group (p<0.001). A total of 8.4% (31/368) and 3.2% (8/252) of patients underwent BPH-related surgery in the α-blocker and combination groups, respectively (p=0.008). According to the follow-up period, the incidence of AUR was significantly decreased in combination group. However, the incidence of BPH-related surgery was significantly reduced after 7 years of combination therapy. Cutoff levels of PSA and PV for reducing the incidences of AUR and BPH-related surgery were 2.0 ng/ml and 35 g, respectively (p<0.001).ConclusionsLong-term combination therapy with α-blocker and 5-ARI can suppress the progression of BPH more efficiently than α-blocker monotherapy. For patients with BPH with PSA >2.0 ng/ml or PV >35 ml, combination therapy promises a better effect for reducing the risk of BPH progression.

Comorbid social withdrawal (hikikomori) in outpatients with social anxiety disorder: Clinical characteristics and treatment response in a case series

Severe social withdrawal (called hikikomori, and defined as isolation lasting more than six months and not due to an apparent mental disorder) has drawn increasing public attention in Japan. It is unclear whether hikikomori is merely a symptom or syndrome of social withdrawal. To evaluate this phenomenon in relationship to social anxiety disorder (SAD), as few previous studies have. One hundred and forty-one consecutive patients with SAD diagnosed according to DSM-IV criteria by a semi-structured interview were treated with a combination of psychotherapy, pharmacotherapy and group activity. Twenty-seven (19%) SAD patients fulfilled the criteria for hikikomori, and these patients had earlier onset, more symptoms and less education than non-hikikomori SAD patients. Only 33% of hikikomori SAD patients spontaneously complained of SAD symptoms at first visit. There were no diagnostic differences between hikikomori and non-hikikomori SAD patients, except that comorbid obsessive-compulsive disorder was more frequent in hikikomori SAD patients. Functional impairment in 10 (37%) hikikomori SAD patients improved after several years of combination therapy. Hikikomori may serve as a proxy for a severe form of SAD. Patients with comorbid SAD and hikikomori have lower treatment response rates than those with SAD alone.

No more pilots, a phase III trial of fibrates in primary biliary cirrhosis is long overdue!

No more pilots, a phase III trial of fibrates in primary biliary cirrhosis is long overdue!

Disappearance of Angina Pectoris by Lipid-Lowering in Type III Hyperlipoproteinemia

Type III hyperlipoproteinemia is a rare familial disease characterized by marked elevations of serum cholesterol and triglyceride levels caused by an accumulation of remnant lipoproteins in apolipoprotein E2/E2 homozygotes. It is associated with an increased risk for premature atherosclerotic vascular disease. A 55-year-old woman was diagnosed as having type III hyperlipoproteinemia on the basis of skin lesions, serum lipid levels, lipid electrophoresis, and apolipoprotein E genotyping and stable angina pectoris on the basis of typical symptoms and treadmill exercise electrocardiographic results. After 1 year of combination therapy with atorvastatin and fenofibrate, skin xanthomata disappeared, leaving minimal remnants. In addition, there was no exertional chest pain, and treadmill exercise electrocardiographic results were negative. This finding was confirmed by coronary computed tomographic angiography. This case suggests that proper medical therapy can induce the regression of uncomplicated coronary lesions in type III hyperlipoproteinemia.

Resolution of chronic hepatitis Delta after 1 year of combined therapy with pegylated interferon, tenofovir and emtricitabine

Background Hepatitis Delta virus (HDV) Infection has a worldwide distribution, with approximately 20 millions infected persons. Interferon (IFN) is the only approved drug for the treatment of HDV infection which is still a difficult to treat disease. Objectives To report a successful treatment of a patient with a chronic severe hepatitis Delta using combination therapy with Pegylated interferon (PegIFN), Tenofovir disoproxil fumarate (TDF) and Emtricitabine (FTC). Study Design The patient, a 47 years -old male patient, originating from Dagestan (East Asia), suffered of chronic hepatitis Delta infection. The patient was HBsAg, HBeAg, and anti-Delta Ab (IgG) positive. Serum HBV-DNA level was elevated (more than 9 logUI/mL). Serum HDV-RNA level was up to 5.6 log (copies/ml). Genotypes HBV/D and HDV-1 were demonstrated. The liver histology revealed chronic active hepatitis (Metavir score: A2F2). The treatment was started with PegIFN (180 μg/week) for two months and then TDF (300 mg/day) (combined later with FTC) was added. Results Sustained response was obtained after 10 months of treatment and was accompanied by the clearance of serum hepatitis B virus surface antigen with seroconversion to anti-HBs. Conclusion This case report suggests that Delta infection may co-exist with high replicative HBV infection and that combination therapy with PegIFN and nucleoside/tide analogues seems to be more effective than IFN alone. Given that only a single case is reported, further studies including more patients are warranted.

Hepatocellular carcinoma in the absence of liver cirrhosis in a treated hepatitis C virus patient.

To the Editor: A 65-year-old male patient was referred to King Faisal Hospital and Research Centre after he presented with jaundice, fever, abdominal discomfort and biochemical evidence of chronic hepatitis C virus (HCV) hepatitis with no clinical or histological evidence of cirrhosis. HCV polymerase chain reaction (PCR) was positive and HCV quantitation was 4682 copies/mL. Liver function test (LFT) results were ALT 225 IU/L (reference range, 5-60 IU/L), AST 104 IU/L (reference range, 5-43 IU/L), total bilirubin 20 μml/L (reference range, 5.1-17.0 μmol/L), INR 1.2 (reference range, 0.9-1.1), and albumin 38 g/L (reference range, 35-50 g/L). Liver biopsy showed chronic hepatitis grade II, stage II portal fibrosis and no evidence of cirrhosis. Alpha-fetoprotein was 6 μgm/L. The patient completed a full year of combination therapy of pegulated interferon 3 million units subcutaneously 3 times/week with ribavirin 1000 mg orally daily and achieved a negative viral PCR with normal LFTs. He had 3 years of follow-up with a sustained virological response (sustained loss of detectable virus in response to antiviral therapy) and was then discharged from our clinic and instructed to follow-up at his local hospital. A CT scan at discharge showed no evidence of cancer (image not available). Two years later he was referred back from his local hospital with a huge right hypochondrial mass associated with pain but no jaundice, fever or weight loss. The mass was about 10 cm in diameter, difficult to separate from the liver, ill-defined, lobulated and hard. Basic tests, including CBC and renal profile were normal. ALT 27 IU/L (reference range, 5-60 IU/L), AST 35 IU/L (reference range, 5-43 IU/L), ALP 75 IU/L (reference range, 30-120 IU/L), total bilirubin 14 μml/L (reference range, 5.1-17.0 μmol/L), INR 1.0 (reference range, 0.9-1.1), and albumin 42 g/L (reference range, 35-50 g/L). AFP was 2.3 μgm/L and carcinoembryonic antigen (CEA) was 2.1 μgm/L. Ultrasound of the abdomen showed a huge liver mass (8cm×11cm) and the right portal vein branch was not visualized distally. CT of the abdomen showed the same mass at segment 5 and 8 which was consistent with hepatocellullar carcinoma (HCC) showing the classical triphasic pattern, i.e., heterogenous enhancement in the arterial phase, but early rapid washout in the portal-venous phase leaving the HCC lesion hypo-dense compared to the surrounding normal tissue (Figure 1). The patient underwent surgical removal of both segments (5 and 8). Histopathology of the mass confirmed the diagnosis of HCC. H&E stain showed the HCC pseudoglandular and trabecular pattern (Figure 2) and extensive lymphovasculer invasion. Immunohistochemical stain for CD34 was positive and showed wrapping of the tumor cluster by endothelial cells. The rest of the non-neoplastic livers showed only mild steatosis and no cirrhosis at all (Trichrome stain) (Figure 3).

Indications for Dual Antiplatelet Therapy with Aspirin and Clopidogrel: Evidence-Based Recommendations for Use

To review the literature assessing dual antiplatelet therapy with aspirin and clopidogrel and subsequently provide evidence-based recommendations for appropriate indications and length of therapy. An English-language MEDLINE search (1950-December 2007) was conducted using the search terms antiplatelet, aspirin, thienopyridine, and clopidogrel to identify articles assessing dual antiplatelet therapy. Evaluation of references from identified trials for possible inclusion was also conducted. All studies that assessed treatment with the combination of aspirin and clopidogrel for any indication were included. Aspirin and clopidogrel have complementary mechanisms of action to inhibit platelet function. Indications that have been studied include coronary artery disease (CAD), atherosclerotic ischemic stroke, and atrial fibrillation. This combination has been beneficial in patients with acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), and in PCI patients without an acute event. There is a small but significant risk for increased bleeding with dual antiplatelet therapy for these indications. When used in patients with a history of atherosclerotic ischemic stroke or for prevention of cardioembolic stroke in patients with atrial fibrillation, this combination has been shown to increase bleeding, providing no clinical benefit, and to increase outcomes including stroke, myocardial infarction, and death, respectively. There is evidence to support use of aspirin in combination with clopidogrel for patients presenting with all ACS types, as well as for patients presenting with PCI for any indication. The treatment duration varies, but patients who have received stenting should receive at least 1 year of combination therapy. There is no evidence to support this combination for primary prevention of CAD or atherosclerotic ischemic events, secondary prevention of stable CAD, or prevention of cardioembolic stroke in patients with atrial fibrillation. The possible benefits of dual antiplatelet therapy also must be weighed against the risk of bleeding.

A randomized controlled 1-year study of daily deferiprone plus twice weekly desferrioxamine compared with daily deferiprone monotherapy in patients with thalassemia major

The aim of this prospective, randomized, 1-year study was to compare the efficacy and safety of oral deferiprone (DFP) with those of combinations of parenteral desferrioxamine (DFO) with oral DFP. A total of 24 patients with thalassemia major were randomized to receive one of the following two treatments; DFP given at a daily dose of 75 mg/kg in combination with DFO (40-50 mg/kg twice weekly) (n=12) or as single agent (n=12). In addition, 12 patients treated with 40-50 mg/kg DFO 5 days weekly were included as a reference group without randomization. Changes in liver iron concentration (LIC) and serum ferritin (SF) were assessed; total iron excretion (TIE), urinary iron excretion (UIE) and iron balance were calculated. Cardiac function and toxicity were also examined. SF and LIC were significantly reduced after 1 year of combination therapy (p=0.01 and 0.07, respectively). A decrease of LIC was observed in all but one patient (87.5%) following the combination therapy but in only 42% of patients treated with DFP monotherapy. In the DFO reference group, a statistically significant decrease in LIC (p=0.01) associated with a substantial decrease in SF (p=0.08) was observed after 1 year. The combination regimen resulted in greater TIE compared to DFP monotherapy (p=0.08) and was the regimen associated with the highest iron balance compared to DFP monotherapy (p=0.04) or standard DFO treatment (p=0.006). The addition of subcutaneous DFO twice weekly to oral DFP 75 mg/kg is a highly efficacious and safe chelation therapy providing superior chelation activity to that of DFP and likely has an efficacy profile comparable to that of standard DFO.

Low Resistance to Adefovir Combined With Lamivudine: A 3-Year Study of 145 Lamivudine-Resistant Hepatitis B Patients

Adefovir monotherapy is an established treatment modality for lamivudine-experienced patients with chronic hepatitis B, but it carries a significant risk of resistance in the long term. We assessed whether this risk could be overcome by adefovir-lamivudine combination therapy. A total of 145 lamivudine-resistant patients with chronic hepatitis B (73% cirrhotics, 86% hepatitis B e antigen negative, 92% genotype D) were treated with adefovir 10 mg in addition to lamivudine 100 mg. Liver function tests and hepatitis B virus (HBV) DNA (Versant 3.0) were assessed bimonthly, whereas adefovir-related mutations were searched by INNO-LiPA assay at baseline and at yearly intervals. During 42 months (range, 12-74), 116 patients (80%) cleared serum HBV DNA, 67 (84%) had normalized alanine aminotransferase levels, and 145 (100%) remained free of virologic and clinical breakthroughs, independently of the degree of HBV suppression. The rtA181V/T was the only adefovir-related mutation detected, which occurred in 6 patients at baseline (4%; 1 rtA181V and 5 rtA181T) and in an additional 3 patients (2%; all rtA181T) during treatment. In all these 9 patients, HBV DNA levels progressively declined during therapy to become undetectable in 7 (78%). The 1-, 2-, 3-, and 4-year cumulative rates of de novo rtA181T were 1%, 2%, 4%, and 4%, respectively. None of the cirrhotic patients clinically decompensated, but 11 (12%) developed hepatocellular carcinoma. Under prolonged adefovir-lamivudine therapy, patients with lamivudine-resistant hepatitis B were unlikely to develop genotypic resistance to adefovir and had durable prevention of virologic and clinical breakthrough.

Navigating the Maze of Hepatitis B Treatments

Navigating the Maze of Hepatitis B Treatments

Effect of Metformin and Rosiglitazone in a Prepubertal Boy with Alström Syndrome

Alström syndrome (AS) is an autosomal recessive disorder characterized by progressive pigmentary retinopathy, sensorineural hearing loss, fatty liver infiltration, obesity, insulin resistance and early-onset type 2 diabetes mellitus (DM2). Early onset of insulin resistance and DM2 are key components of this syndrome. To study the effect of early initiation of the insulin sensitizer metformin combined with rosiglitazone in a patient with AS with impaired glucose tolerance. An 8 year-old boy with AS presented with acanthosis nigricans and insulin resistance at the age of 6 years. He had progressive excessive weight gain from 9 months of age. By the age of 1 year he developed photosensitivity, blindness and nystagmus. At the age of 5.5 years, his body mass index (BMI) was above the 95th percentile. He developed impaired glucose tolerance at 6 years of age and treatment with metformin was initiated. After 8 months of treatment with metformin he developed DM2. The dose of metformin was increased, and rosiglitazone added. A 2-hour oral glucose tolerance test (OGTT) and a rapid intravenous glucose tolerance test (IVGTT) were performed before treatment was initiated, after treatment with metformin and at the end of 1 year of combination therapy with metformin and rosiglitazone to calculate quantitative insulin sensitivity check index (QUICKI) and acute insulin response (AIR). For mutation analysis, all exons and splice site sequences of the ALMS1 gene were amplified and sequenced. Metformin treatment alone at the stage of impaired glucose tolerance did not prevent progression to DM2. However, metformin at a higher dose and in combination with rosiglitazone resulted in improvement of pancreatic beta-cell function, shown by markedly improved first-phase insulin response to glucose measured by AIR. The patient was found to have two heterozygous nonsense mutations in ALMS1, 8008 C-->T Ter, R2670X, and 11449 C-->T Ter, Q3817X. These alterations cause premature stops and result in a truncated ALMS1 protein. We suggest that early initiation of combined therapy comprising a high dose of metformin plus rosiglitazone may be valuable in managing insulin resistance and DM2 in children with AS.

Maintenance Therapy with Low Dose Thalidomide, Dexamethasone and Clarithromycin (Biaxin) (BLT-D) Following Autologous Transplant (ASCT) for Multiple Myeloma (MM).

Relapse remains a major problem after a standard ASCT for MM. Strategies to prevent relapse have included post transplant maintenance therapy. M Coleman et al (Leukemia and Lymphoma 43:1777–1782, 2002) pioneered a regimen of BLT-D to treat in a non-transplant setting MM and reported a high CR/PR response rate (93%). Since the BLT-D regimen showed significant disease response, it seemed reasonable to study this regimen as maintenance therapy after ASCT. Between 7/2003–1/2006, 23 patients (stage II, n=6 and stage III (n=17) were treated. 26% of patients had poor prognostic cytogenetics. 61% had elevated beta 2 microglobulin at initial diagnosis; 30% still had elevated beta 2 microglobulin at time of ASCT. 48% of the patients had received Thalidomide therapy before ASCT. All were conditioned for ASCT with melphalan 200 mg/m2. 30–120 days after recovery from the acute toxicity of ASCT, patients were treated with Biaxin 250 mg po bid, Dexamethasone 20 mg po q week and Thalidomide beginning at 50 mg po daily for 14 days, then increased to 100 mg po daily. After one year of combination therapy, Biaxin and Dexamethasone were stopped and Thalidomide was continued as long as tolerated or until disease progression. The median time to starting therapy was 102 days (range 40–120) post ASCT. Neuropathy was the most common toxicity. Four patients stopped therapy because of significant peripheral neuropathy and four patients required dose reduction of Thalidomide because of neuropathy. Eight patients had reduction in Dexamethasone dosing because of toxicity. One patient stopped Biaxin for rash. Number of infections seen included pneumonia (n=3), viral upper respiratory infection (n=2), sinusitis (n=1) and bronchitis (n=3). One patient withdrew from therapy to undergo elective second ASCT. Three patients have died: infection (n=1), MM progression (n=1) and complications of second ASCT (n=1). In patients who still had detectable MM after ASCT prior to beginning BLT-D therapy, 46% of the evaluable patients to date have been shown to go into complete remission on BLT-D therapy. Three patients have progressed. 18 (78%) out of 23 patients remain alive without disease progression. Median follow-up is 20.5 months (range 6–25). Further follow-up is needed to determine the effect of BLT-D upon relapse and survival of MM ASCT patients.

Efficacy of Sildenafil as a Rescue Therapy for Patients With Severe Pulmonary Arterial Hypertension and Given Long-term Treatment With Prostanoids: 2-Year Experience

Both prostanoids and sildenafil are effective treatments for severe pulmonary arterial hypertension (PAH). The combined use of these drugs to maximize the clinical benefit is an emerging treatment option. This study describes a 2-year experience with adjunct sildenafil as a rescue therapy for patients with severe PAH treated long term with prostanoids and who showed clinical deterioration or onset of heart failure. Twenty patients (11 men, 9 women; mean age 42 +/- 11 years) with severe PAH, who showed clinical or functional worsening despite ongoing treatment with prostanoids (8 subcutaneous, 7 intravenous, 5 inhaled), were started on adjunct oral sildenafil. New York Heart Association (NYHA) functional class, 6-minute walking test, signs of right ventricular failure and echocardiography were assessed before and after 1 and 2 years of combined therapy. There was a significant improvement of NYHA functional class and signs of right heart failure after 1- and 2-year follow-up. Patients showed a mean increase in 6-minute walking distance of 79 m and 105 m after 1 and 2 years of adjunct sildenafil, respectively. Two patients died during follow-up. The echocardiographic parameters showed a significant reduction of right ventricular end-diastolic diameter and left ventricular diastolic eccentricity index. No serious side effects related to sildenafil were observed. Adjunct sildenafil to long-term prostacyclin therapy in patients with severe PAH provided sustained clinical stabilization and an improved clinical situation, exercise capacity and echocardiographic parameters of right ventricular function. The beneficial effects were strong and lasted >24 months.

Ultrasonographic and radiographic results from a two‐year controlled trial of immediate or one‐year–delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis

To compare the impact of immediate and delayed introduction of anti-tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)-treated patients with early rheumatoid arthritis (RA). Twenty-four patients with erosive early RA (duration < 3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high-frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system. From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between-group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076). The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.

Metastatic pancreatic adenocarcinoma in complete remission after three and a half years of combination therapy with cetuximab

4278 Background: Ductal adenocarcinoma of the exocrine pancreas has a poor prognosis with one-year survival rates of around 10% and 5-year survival of less than 4%. Long-term survivors derive from patients with resectable disease at the outset, who constitute less than 20% of the total diagnosed, while median survival with metastatic disease remains less than 6 months. To improve the outcome in a patient with advanced disease at presentation, the addition of the EGFR-targeting monoclonal antibody Cetuximab to the standard available therapies was used. Methods: A 49 year old male was diagnosed as having a poorly-differentiated adenocarcinoma of the pancreas body and tail with liver metastases. He received Docetaxel and Irinotecan for 30 weeks before and 15 weeks after surgical resection of the primary tumour and hepatic metastatectomy. On liver relapse (evident on MRI and PET scans), Gemcitabine and Oxaliplatin were used for 58 weeks resulting in complete remission (CR) radiologically (on CT, MRI and PET scanning) and pathologically (on repeat laparotomy and biopsies). Cetuximab was administered from the first day of treatment and then throughout, subsequently now being continued for over one year as maintenance monotherapy following documentation of CR. His formal consent was obtained for presentation of his case history. Results: Overall therapy very well tolerated, with excellent long term quality of life. Maximal toxicity recorded involved nausea and vomiting (G3) on the initial chemotherapy; peripheral sensory neuropathy (G2) and hypersensitivity (G3) from Oxaliplatin; neutropoenia (G4) but only after 27 months from starting chemotherapy; skin toxicity (G2) due to Cetuximab, settling over time. CR has been maintained now for 18 months, with the patient currently remaining disease-free on single agent Cetuximab at 3.5 years after diagnosis with metastatic pancreatic adenocarcinoma. Conclusions: These observations in a single patient suggest a benefit for long-term Cetuximab in pancreatic carcinoma. Long term use, including peri-operative administration, appears to be safe and well tolerated. Further evaluation of Cetuximab in this disease is recommended. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck, sanofi-aventis Merck, sanofi-aventis

TELMISARTAN IN THE TREATMENT OF HYPERTENSION IN PATIENTS WITH CHRONIC RENAL INSUFFICIENCY

The primary aim of this study was evaluation of the efficacy of telmisartan (angiotensin II receptor blocker- AT(1) blocker) on blood pressure in 10 patients with renal impairment in moderate or advanced stages of renal insufficiency and not dependent on haemodialysis. Its effect on proteinuria, renal function (represented by serum urea, creatinine, glomerular filtration), evaluation of overall therapy compliance in comparison with a previously prescribed angiotensin converting enzyme inhibitors (ACEI) were secondary aims. Considering the presence of left ventricle hypertrophy in all patients as a marker of hypertensive cardiopathy, the effect of telmisartan therapy on non-invasive cardiovascular parameters (ECG, echocardiography, and assessment of heart rate variability-HRV) was also evaluated. The study group involved 10 hypertensive patients (6 women, 4 men) with diabetic and non-diabetic renal impairment, proteinuria above 1 g/24 hours, hypertensive cardiopathy and intolerance of ACEI (cough). Telmisartan was added to their long-term antihypertensive combination therapy in a dose of 40 mg for the first 14 days, after which the dose increased to the maximal of 80 mg. The average initial daytime systolic blood pressure (SBP) was 149 +/- 19.7 mm Hg, average night-time SBP 145 +/- 23.0 mm Hg, average initial daytime diastolic BP (DBP) 90.6 +/- 2.5 mm Hg, night-time DBP 88.9 +/- 13.5 mm Hg. Average initial serum creatinine was 207.2 +/- 48.5 micromol/l, urea 15.1 +/- 4.4 mmol/l, GF 0.5 +/- 0.1 ml/s. Echocardiography revealed left ventricular (LV) hypertrophy with well preserved systolic and moderately impaired diastolic LV function. Also the HRV assessment revealed impaired neurovegetative (e.g. sympathovagal) balance. After 1 year of combination therapy with telmisartan, there was a clearly significant reduction in both SBP and DBP in both day and night-time (SBP daytime 149.6 vs.116.6 mm Hg, night-time 145.8 vs. 129.5 mm Hg; DBP daytime 90.6 vs. 83.5 mm Hg, night-time 88.9 vs. 79.3 mm Hg) and proteinuria (2.37 vs. 1.27 g/24 hour, p < 0.05). There were no significant changes in serum creatinine, urea values, and LV functions. On the other hand, further progression of the sympathovagal balance impairment was noted (continuing reduction of HRV in 9 from 10 patients), which can be described as the priority finding. The total compliance of telmisartan therapy was very good and without adverse clinical side effects. In conclusion - telmisartan reduces blood pressure and proteinuria safely and effectively in patients with various types of nephropathy in moderate or advanced stages of renal insufficiency.