Effectiveness and safety of pemetrexed for non-small cell lung cancer in the Andalusian Public Health System.

OBJECTIVE: To evaluate effectiveness and safety profile of pemetrexed in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) when it´s used on real clinical practice in Andalusia (a Spanish region with 8.5 million inhabitants, 2014 census data). METHODS: An observational multicentre retrospective study was conducted. Adult patients with locally advanced/metastatic NSCLC who received pemetrexed in any hospital in the Andalusian Public Health System during the last term of 2011 were included. We collected patients´ baseline characteristics, diagnostic and treatment data, effectiveness variables (response to treatment with pemetrexed and overallsurvival) and main adverse reactions detected. RESULTS: 172 patients from 17 hospitals were included (77.33% were men), median age 63 years old (between 34 and 83). The predominant histology was adenocarcinoma (84.30%) and 85.20% were diagnosed of lung cancer with IV-stage. 78.49% had been smokers at some point in their lives. Median overall survival from the start of pemetrexed was 9 months (95%CI, 4.1-13.9). Progression of the disease was the most frequent response (33.14%), only one patient had complete response. Stable disease was associated with a higher probability of survival. Main adverse reactions detected were asthenia, haematological reactions, gastrointestinal reactions and dermal o mucous toxicity. No patients discontinued treatment for serious toxicity. CONCLUSIONS: Pemetrexed resulted quite effective in NSCLC when it was used on real clinical practice, with higher survival in non-squamous histology and patients with the best score of Eastern Cooperative Oncology Group scale. The toxicity profile was well tolerated. Prospective studies would be needed to confirm the effect of prognostic factors observed.

Objetivo: Evaluar la efectividad y el perfil de seguridad del pemetrexed en pacientes con cáncer de pulmón no microcítico (CPNM) localmente avanzado o metastásico en la práctica clínica real en Andalucía (una región española con 8,5 millones de habitantes según los datos del censo de 2014). Métodos: Se realizó un estudio retrospectivo multicéntrico observacional, incluyendo aquellos pacientes adultos con CPNM localmente avanzado/metastásico que hubiesen recibido pemetrexed en cualquier hospital del Sistema Sanitario Público de Andalucía durante el último trimestre de 2011. Se revisaron las características basales de los pacientes, los datos relativos al diagnóstico y al tratamiento, las variables de efectividad (en términos de respuesta al tratamiento con pemetrexed y supervivencia global) y las principales reacciones adversas detectadas. Resultados: Se incluyeron un total de 172 pacientes procedentes de 17 hospitales (77,33% hombres), con una mediana de edad de 63 años (rango: 34 y 83). La histología predominante fue el adenocarcinoma (84,30%) y el 85,20% fueron diagnosticados de cáncer de pulmón en estadio IV. El 78,49% habían sido fumadores en algún momento de sus vidas. La mediana de supervivencia global desde el inicio del pemetrexed fue de 9 meses (IC del 95%, 4,1-13,9). La progresión de la enfermedad fue la respuesta al tratamiento más frecuente (33,14%) y solo un paciente tuvo una respuesta completa. La presencia de enfermedad estable se asoció con una mayor probabilidad de supervivencia. Las principales reacciones adversas detectadas fueron astenia; reacciones hematológicas, gastrointestinales y dermatológicas o toxicidad mucosa. Ninguno de los pacientes interrumpió el tratamiento por toxicidad grave. Conclusiones: El pemetrexed resultó bastante efectivo en el CPNM cuando fue utilizado en la práctica clínica real, con una mayor supervivencia en histología no escamosa y en los pacientes con mejor puntuación en la escala Eastern Cooperative Oncology Group. El perfil de toxicidad fue bien tolerado. Serían necesarios estudios prospectivos para confirmar el efecto de los factores pronósticos observados.

Continuous versus intermittent piperacillin/tazobactam infusion in infection due to or suspected pseudomonas aeruginosa.

BACKGROUND: There is lack of information on the efficacy and safety of piperacillin­tazobactam administered by continuous infusion. OBJECTIVE: The aim of this study was to investigate whether continuous infusion of piperacillin­tazobactam is superior in terms of efficacy to a 30 % higher dose administered by intermittent infusion to treat suspected or confirmed infection due to Pseudomonas aeruginosa. Setting Multicenter clinical trial with 11 third level Spanish hospitals. METHOD: Randomized, double-blind parallel-group clinical trial, controlled by conventional administration of the drug. Patients randomly assigned in a 1:1 ratio to receive piperacillin­tazobactam as continuous infusion (CI) or intermittent (II). MAIN OUTCOME MEASURE: Primary efficacy endpoint was percentage of patients having a satisfactory clinical response at completion of treatment, defined as clinical cure or clinical improvement. Adverse events were reported. Results 78 patients were included, 40 in the CI group and 38 in the II group. Mean (standard deviation) duration of treatment was 7 (±4.44) days. 58 patients (74.4 %) experienced cure or improvement at the end of the treatment. There were no statistical differences in cure rates between the two treatment arms and no adverse events were reported. CONCLUSION: Continuous infusion of piperacillin­tazobactam is an alternative administration drug method at least similar in efficacy and safety to conventional intermittent infusion. Multivariate analysis is needed to determine whether continuous administration might be more beneficial than intermittent in certain patient subgroups.

Use of pemetrexed for non-small cell lung cancer in the Andalusian public health system.

The aim of this study is to determine the profile of the use of pemetrexed in metastatic or locally advanced NSCLC in Andalusia and its variation over 2 years (2010-2011). A prescription-indication observational retrospective multicenter study was conducted. Adult patients with locally advanced/metastatic NSCLC who received pemetrexed in any hospital in the Andalusian Public Health System during the first term of 2010 or the last term of 2011 were included. We collected patients' baseline characteristics, tumour histology and stage, pemetrexed indication and performance status at the start of treatment. In all, 107 and 170 patients (62 ± 11 years old) from 17 hospitals were included in 2010 and 2011, respectively. The predominant histology was adenocarcinoma (85%), 88% of patients had stage IV tumours and 52% Eastern Cooperative Oncology Group stage (ECOG) 1. Pemetrexed indications in 2010 and 2011 were: First line combined with platinum (28.97-37.64%); first line combined with platinum and maintenance with pemetrexed (24.30-28.82%); second line mono-therapy (12.15-7.65%) and maintenance (2.15-7.05%). Off-label use was detected in 22.43% (2010) and 18.84% (2011). In conclusion, pemetrexed combined with platinum is mainly used as first-line treatment in NSCLC patients with stage IV, adenocarcinoma histologic subtype and good performance status. Off-label use is high (especially in 2010). An adequate therapeutic positioning for pemetrexed based on effectiveness and safety analysis should be defined, so that NSCLC patients could be beneficiated with the most cost-effective chemotherapy treatment.

Systematic review of efficacy and safety of pemetrexed in non-small-cell-lung cancer.

INTRODUCTION: Lung cancer accounts for 20 % of cancer deaths in Spain. The most frequent subtype (87 %) is non-small cell lung cancer (NSCLC). Pemetrexed is a recently marketed drug added to NSCLC therapeutic arsenal. It seems to have become one of the most used options for the treatment of this condition over the last 3 years. AIM OF THE REVIEW: To evaluate the efficacy and safety of pemetrexed in NSCLC, in the different therapy lines. Method A systematic search of published literature was conducted using the main databases (MEDLINE, EMBASE, the Cochrane Library and the Center for Reviews and Dissemination) and subsequently a search of referenced literature was performed. We included clinical trials, meta-analyses and systematic reviews. The evaluation of the quality of the articles was performed by pairs using specific assessment scales, Critical Appraisal Skills Program (CASP) adapted for CASP Spain. Then we extracted data on efficacy and safety according to the treatment line assessed. RESULTS: We identified 277 references. Finally, nine clinical trials and a meta-analysis complied with inclusion criteria. In first-line induction, treatment with pemetrexed associated with a platinum was similar in terms of efficacy to other alternative chemotherapy regimens, except in patients with non-squamous histology, in whom survival was higher in the experimental group. In maintenance treatment, greater efficacy was seen with pemetrexed in patients with non-squamous histology. In second-line treatment, there were no significant differences in terms of efficacy and safety for pemetrexed treatment versus other chemotherapy options. The most frequent adverse reactions were: hematological, gastrointestinal and neurological. All were significantly less frequent with pemetrexed versus other alternative therapies, except for liver toxicity. CONCLUSIONS: Due to the high degree of uncertainty as to its efficacy in certain subgroups of patients, including conflicting data; to its recent incorporation, and therefore lack of safety data in the medium and long term, and the high budgetary impact of its incorporation into health systems, it seems reasonable to optimize its use, identifying those patients who may benefit most.