Time to initiate randomized controlled clinical trials with methadone in cancer patients.

Public media coverage has fueled a demand for methadone as potential cure for cancer itself. Because patients have asked for respective prescriptions, clinical societies issued statements warning against the use of methadone as long as preclinical findings have not been supported by clinical evidence. In fact, not all preclinical data clearly support relevant effects. However, strong epidemiologic data suggest beneficial effects of methadone on cancer. Alternative explanations, namely better safety of methadone or hidden selection bias, seem less likely. This uncertainty can only be resolved by randomized controlled clinical trials. This review discusses all relevant data pertinent to methadone and cancer, uncovers supportive epidemiologic data, and suggests possible study designs.

Treatment of multiple, multiform actinic keratoses on the head with imiquimod 5% cream.

The objective of this non-controlled interventional clinical study was to evaluate the efficacy of imiquimod in the treatment of fields with multiple, multiform AK. 180 office-based dermatological practices in Germany participated. Patients with clinically typical, visible AK lesions on the head were treated with 5% imiquimod cream 3 times per week for 4 weeks followed by a 4 week treatment pause. If lesions were still present, a second treatment course of treatment (COT) was given. Complete clearance rate, i.e. no clinically visible AK lesions in the treatment area, was the main outcome measure. 829 patients were enrolled. The complete clearance rate was 40.5% after the first COT and 68.9% overall. Altogether, 85.4% of the 7,427 baseline lesions were cleared. Patients with hyperkeratotic/hypertrophic lesions showed comparable responses. Local skin reactions were the most commonly reported adverse effects, causing discontinuation in only 4 patients. Severity of the local skin reactions was a strong predictor of the outcome. Patients with multiple multiform AK on the head can be successfully and safely treated with topical imiquimod in daily practice. Assurance of patient understanding that treatment success is closely correlated to proper drug administration is important.

Prevention of exercise-induced asthma by a fixed combination of disodium cromoglycate plus reproterol compared with montelukast in young patients.

BACKGROUND: The leukotriene inhibitor montelukast has been recommended against exercise-induced asthma (EIA), however, single-dose agents might be favourable in several aspects. OBJECTIVE: To compare the protective effects against EIA of a single inhalation of the combination disodium cromoglycate (DSCG, CAS 16110-51-3) and reproterol (REP, CAS 54063-54-6) with 3 days oral treatment of montelukast (MON, CAS 158966-92-8). METHODS: Open-label, cross-over, single-centre trial. Twenty-four 6 to 18-year-old children and adolescents, with reversible and stable airway obstruction, baseline FEV1 > or = 70%, predicted and proven EIA (i.e. a maximum decrease of FEV1 by > or = 20% compared with baseline) were treated with MON, orally for 3 days in the evening, or one single inhalation of DSCG/REP 20 min before the exercise challenge. The treatment sequence was randomised. The exercise test on a treadmill was performed under standardised conditions. RESULTS: 24 patients completed both periods. Both treatments clearly provided protection against EIA; however, protection of DSCG/REP was more pronounced than that of MON. This difference was statistically significant even if the data were adjusted for the increase in FEV1 between inhalation of DSCG/REP and challenge (DSCG/REP(adjusted). The nadir FEV1 level after exercise following prophylaxis with DSCG/REP was even higher than the pre-inhalation FEV1 value. From these data, protection indices of 66%, 81%, and 113% for MON, DSCG/REP(adjusted), and DSCG/REP(unadjusted), respectively, were estimated. CONCLUSIONS: Inhalation of DSCG/REP before exercise provides significantly better protection against EIA than three days treatment with MON.

Single-dose pharmacokinetics and safety pharmacodynamics of formoterol delivered by two different dry powder inhalers.

The present study aimed at assessing the pharmacokinetics (PK) and safety pharmacodynamics (PD) of 24 microg formoterol delivered via a Novolizer and via an Aerolizer in healthy subjects. This was a randomized, open-label, crossover study. Beside PK, serum potassium, and glucose profiles, vital signs, and ECG were recorded. Twenty-nine subjects (15 males) were enrolled. The inhalation maneuver had to be repeated by 19 subjects using the Aerolizer and 1 subject using a Novolizer. While eight (28%) subjects completely failed to inhale correctly via the Aerolizer (four were identified by the investigators immediately after inhalation, another four by bioanalytics later), all did it correctly via the Novolizer. The bioanalytical evaluation indicated two distinct serum peaks. The shapes of serum concentration-time profiles were more homogeneous after inhaling via the Novolizer than via the Aerolizer. After adjusting for the delivered dose the Cmax of formoterol predicting pulmonary absorption was higher after the Novolizer than after the Aerolizer, while the average AUC0-infinity levels indicating total systemic exposure were equivalent. There was no evidence for different pharmacodynamic behavior with respect to serum potassium and glucose profiles, vital signs, and ECG. The Novolizer yields higher pulmonary absorption of formoterol than the Aerolizer and equivalent safety profiles. Considering the lower variability of PK profiles and the higher proportion of correct inhalations, formoterol is more reliably inhaled via Novolizer.

Peak inspiratory flow rates generated through the Novolizer and the Turbuhaler dry powder inhaler devices by children with stable asthma.

We compared the peak inspiratory flows (PIF) generated through a novel dry powder inhaler device, the Novolizer (PIF-N), and the Turbuhaler (PIF-T). Forty-six pediatric patients with stable bronchial asthma were randomized in an open-label, multicenter, crossover trial. No drug was administered during the inhalation maneuvers that were spaced by 10 min. There was neither a carryover nor a sequence effect. The patients were characterized by mean age of 8.5 years, mean FEV(1) of 1.79 L, and mean PIF without any device (baseline, PIF-B) of 185 L/min. Through the devices mean PIF-N of 94 L/min and mean PIF-T of 69 L/min were achieved, calculated from the maxima of three inhalations. This resulted in p < 0.0001 for the difference. The median PIFN/PIF-T ratio was estimated as 1.39. Each child achieved a higher PIF-N than PIF-T and was able to release the feedback mechanisms of the Novolizer indicating sufficient inhalation performance. We conclude that the PIF through the Novolizer is higher than the PIF through the Turbuhaler in stable asthmatic children. The flow rates achieved through the Novolizer allow for sufficient lung deposition even in children as young as 6 years.