Comparison of the efficacy and safety of ciclesonide 160 μg once daily vs. budesonide 400 μg once daily in children with asthma

Ciclesonide is an onsite-activated inhaled corticosteroid (ICS) for the treatment of asthma. This study compared the efficacy, safety and effect on quality of life (QOL) of ciclesonide 160 microg (ex-actuator; nominal dose 200 microg) vs. budesonide 400 microg (nominal dose) in children with asthma. Six hundred and twenty-one children (aged 6-11 yr) with asthma were randomized to receive ciclesonide 160 microg (ex-actuator) once daily (via hydrofluoroalkane metered-dose inhaler and AeroChamber Plus spacer) or budesonide 400 microg once daily (via Turbohaler) both given in the evening for 12 wk. The primary efficacy end-point was change in forced expiratory volume in 1 s (FEV1). Additional measurements included change in daily peak expiratory flow (PEF), change in asthma symptom score sum, change in use of rescue medication, paediatric and caregiver asthma QOL questionnaire [PAQLQ(S) and PACQLQ, respectively] scores, change in body height assessed by stadiometry, change in 24-h urinary cortisol adjusted for creatinine and adverse events. Both ciclesonide and budesonide increased FEV1, morning PEF and PAQLQ(S) and PACQLQ scores, and improved asthma symptom score sums and the need for rescue medication after 12 wk vs. baseline. The non-inferiority of ciclesonide vs. budesonide was demonstrated for the change in FEV1 (95% confidence interval: -75, 10 ml, p = 0.0009, one-sided non-inferiority, per-protocol). In addition, ciclesonide and budesonide showed similar efficacy in improving asthma symptoms, morning PEF, use of rescue medication and QOL. Ciclesonide was superior to budesonide with regard to increases in body height (p = 0.003, two-sided). The effect on the hypothalamic-pituitary-adrenal axis was significantly different in favor of ciclesonide treatment (p < 0.001, one-sided). Both ciclesonide and budesonide were well tolerated. Ciclesonide 160 microg once daily and budesonide 400 microg once daily were effective in children with asthma. In addition, in children treated with ciclesonide there was significantly less reduction in body height and suppression of 24-h urinary cortisol excretion compared with children treated with budesonide after 12 wk.     

APO-1(CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines

Certain B and T cell lines respond to activation signals, e.g.through the antigen receptor, by undergoing apoptotlc cell death.In T cells it has been recently shown that TCR-mediated apoptosisinvolves APO-1/Fas (CD95) receptor-ligand interaction. To investigatewhether the TCR-CD3 complex can trigger alternative apoptosispathways we generated subclones of the T cell line Jurkat whichwere completely resistant towards APO-1-mediated apoptosis.These Jurkat^R cells differed phenotypically from sensitive parentalJurkat^S cells only by the lack of APO-1 protein expression.Although Jurkat^R cells responded normally to anti-CD3 stimulationby expression of APO-1 ligand they failed to undergo anti-CD3-inducedapoptosis. Thus, in Jurkat cells APO-1 -mediated apoptosis wasthe main, and might be the only, mechanism for anti-CD3-inducedcell death. However, BL-60 B cells, highly sensitive to anti-IgM-inducedapoptosis, did not use the APO-1 receptor-ligand system becausethey failed to express APO-1 ligand mRNA. Taken together, ourresults suggest that malignant T and B cell lines may use APO-1receptor-ligand-dependent and -independent antigen receptor-inducedapoptosis pathways respectively. Similarly, differential pathwaysmay be used by T and B cell subsets.     

Neo-adjuvant radio-chemotherapy of epidermoid carcinoma of the esophagus

In spite of progress in surgery and radiation therapy, esophageal squamous cell carcinoma's outlook remains grim with a cure rate of approximately 10%. The high failure rate is not only due to loco-regional failure but also to distant metastasis. The association of preoperative chemotherapy with radiation has gained interest with hope to improve control of this disease. The present pilot study is an alternating treatment of chemotherapy and radiotherapy for poor risk carcinomas of the esophagus, not primarily amenable to surgery. The chemotherapy is composed of Cis-Platinum 60 mg/m2 Day 1 (D), Mitomycin 8 mg/m2 D1 and Vindesin 3 mg/m2 D1 and D8, alternating with radiotherapy twice 20 Gy in fraction of 2 Gy per day. After reevaluation patients are if possible submitted to surgery and if not, to a third course of treatment to a total of 3 courses and 60 Gy. Seventeen patients were entered in our study with 15 evaluable. The radiochemotherapeutic association was overall well tolerated with no toxic deaths due to treatment. Seven patients had symptomatic improvement after the first treatment cycle. The presurgical evaluation showed 8 CR and 3 PR. Eight patients have been operated with 3 pathological CR and 3 PR. Five patients completed the 3 courses of chemo- and radiotherapy (without surgery) with no improvement compared to the workup before the third course. The survival is as follows: among the 8 operated: 4 are alive without evidence of disease and 4 are dead with 2 postoperative deaths and 1 local recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)     

The risk of second cancer (SC) in patients treated for testicular seminoma

The exact risk of second cancer (S.C.) following treatment of testicular seminoma is not well determined in most series. At our institution, 122 patients with pure seminoma were treated by orchidectomy followed by radiation therapy from 1951 to 1986. Six were lost to follow-up. For the 116 remaining patients, the overall 5-, 10-, 15- and 20-year survival probability was 95%, 90%, 87%, and 84%, respectively. Eleven patients developed 12 second cancers, with a cumulative risk of 7%, 16%, and 16% at 10, 15, and 20 years, respectively. Overall, the risk of second cancer was increased (O/E = 1.97, p = 0.023). There were 3 controlateral seminoma (O/E = 50, p = 0.001), 2 transitional carcinoma of the bladder (O/E = 6.9, p = 0.035), 2 non-Hodgkin's lymphoma (N.S.), 1 acute myeloblastic leukemia, 1 chronic lymphocytic leukemia, 1 intracranial dysgerminoma, 1 rectal and 1 lung adenocarcinoma. Four tumors developed within the previously irradiated field (O/E = 2.2, N.S.). Excluding second seminoma, the overall risk of second cancer was not significant (O/E = 1.33). Five of the 11 patients with second cancer are currently alive without recurrent cancer. We conclude that patients treated for seminoma have an increased risk of second cancer but the overall prognosis remains excellent. The potential factors responsible for second cancer, including irradiation, are discussed.     

Comparison of the efficacy of ciclesonide 160 microg QD and budesonide 200 microg BID in adults with persistent asthma: a phase III, randomized, double-dummy, open-label study

OBJECTIVE: The efficacy of ciclesonide 160 mug QD (given either in the morning or evening) was compared with budesonide 200 mug BID in adults with stable asthma that was pretreated with inhaled corticosteroids. METHODS: This was a randomized, 3-arm, parallel-group study comparing ciclesonide (given in a double-blind, double-dummy regimen) with open-label budesonide. After 2 to 2.5 weeks, during which patients were treated with budesonide 200 microg BID, patients (n = 405) were randomly assigned to receive ciclesonide 160 microg QD AM or 160 microg QD pm, or budesonide 200 microg BID (all administered by metered-dose inhaler) for 12 weeks. All patients received 2 puffs of medication (or placebo) in the morning and evening. The primary efficacy variable was the difference in spirometric forced expiratory volume in 1 second (FEV(1) in liters) from randomization to study end. Secondary efficacy end points were forced vital capacity, peak expiratory flow by spirometry, and diary assessments of peak expiratory flow, asthma symptoms, and rescue medication use. Adverse events were assessed by patient report, investigator observation, physical examination, and laboratory testing; events were classified as mild, moderate, or severe. RESULTS: Baseline demographic characteristics with regard to sex, age, weight, smoking status, baseline medication use, and FEV(1) were balanced among the treatment groups. Over the course of treatment, both ciclesonide and budesonide maintained FEV(1) compared with baseline. Both ciclesonide regimens were as effective as budesonide 200 microg BID in maintaining FEV(1) during the treatment period versus baseline (ciclesonide 160 microg QD am: 95% CI, -0.120 to 0.045 vs budesonide; P = NS; ciclesonide 160 microg QD pm: 95% CI, -0.061 to 0.105 vs budesonide; P = NS). Ciclesonide 160 microg QD (morning or evening) was comparable with budesonide 200 microg BID for maintaining pulmonary function, asthma symptom scores, and rescue medication use. The incidence of adverse events was not significantly different among the treatment groups, and most adverse events were not related to study medication. CONCLUSIONS: In this study, ciclesonide 160 microg QDwas as effective as budesonide 200 microg BID (400 microg total daily dose) in these adults with persistent asthma. Both treatments were well tolerated.     

Effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis.

BACKGROUND: Ciclesonide is an investigational corticosteroid under development for treatment of allergic rhinitis. Ciclesonide is converted to active metabolite, desisobutyryl-ciclesonide (des-CIC), by upper and lower airway esterases. In vitro studies in human nasal epithelial cells and bronchial epithelial cells have demonstrated a long duration of anti-inflammatory activity of des-CIC. OBJECTIVE: To evaluate the dose-dependent efficacy and safety of a hypotonic intranasal formulation of ciclesonide in patients with seasonal allergic rhinitis (SAR). METHODS: This was a phase 2, randomized, parallel-group, double-blind, placebo-controlled study. Adults (n = approximately 145 per treatment group) with a minimum 2-year history of SAR received placebo or ciclesonide (25, 50, 100, or 200 microg/d) for 14 days. The primary end point was change in the sum of morning and evening reflective total nasal symptom scores (TNSSs) over 2 weeks. Safety was monitored throughout the study. RESULTS: Ciclesonide, 100 microg/d (P = .04) and 200 microg/d (P = .003), significantly improved the sum of morning and evening reflective TNSS vs placebo at more than 2 weeks of treatment. Baseline values for morning and evening reflective TNSS ranged from 17.80 to 18.82 across treatment groups. The average change from baseline in reflective TNSS was -4.2 for placebo and -4.8, -4.8, -5.3, and -5.8 for ciclesonide, 25, 50, 100, and 200 microg/d, respectively. There were no dose-related differences in the incidence of adverse events among treatment groups. CONCLUSIONS: Results from this study indicate that 100-microg and 200-microg daily doses of ciclesonide are effective in the treatment of SAR. Ciclesonide, 200 microg/d, appears to be the optimal dose studied for reducing the symptoms of SAR while maintaining an acceptable safety profile.