A retrospective, multicenter study of the efficacy of lapatinib plus trastuzumab in HER2-positive metastatic breast cancer patients previously treated with trastuzumab, lapatinib, or both: the Trastyvere study.

PURPOSE: To evaluate the efficacy and safety of lapatinib (L) and trastuzumab (T) combination in HER2-positive metastatic breast cancer (MBC) patients previously treated with T and/or L. MATERIALS AND METHODS: We conducted a retrospective, post-authorized, multicenter study including patients with HER2-positive MBC or locally advanced breast cancer (ABC) treated with the combination of L-T. Concomitant endocrine therapy, as well as brain metastasis and/or prior exposure to L, were allowed. RESULTS: One hundred and fifteen patients from 14 institutions were included. The median age was 59.8 years. The median number of prior T regimens in the advanced setting was 3 and 73 patients had received a prior L regimen. The clinical benefit rate (CBR) was 34.8% (95% CI 26.1-43.5). Among other efficacy endpoints, the overall response rate was 21.7%, and median progression-free survival (PFS) and overall survival were 3.9 and 21.6 months, respectively. Heavily pretreated and ≥ 3 metastatic organ patients showed lower CBR and PFS than patients with a low number of previous regimens and < 3 metastatic organs. Moreover, CBR did not significantly change in L-pretreated compared with L-naïve patients (31.5% versus 40.5% for L-pretreated versus L-naïve). Grade 3/4 adverse events were reported in 19 patients (16.5%). CONCLUSION: The combination of L-T is an effective and well-tolerated regimen in heavily pretreated patients and remains active among patients progressing on prior L-based therapy. Our study suggests that the L-T regimen is a safe and active chemotherapy-free option for MBC patients previously treated with T and/or L.

New clinical trials regulation in Spain: analysis of royal decree 1090/2015.

The coming into force of Directive 2001/20/EC represented a step forward in harmonising clinical trial regulation in European countries, guaranteeing a uniform protection of subjects participating in clinical research across Europe. However, it led to a disproportionate increase in the bureaucratization, and thus, it became evident that procedures needed to be simplified without detriment to patient's safety. Thus, Regulation 536/2014, that repealed Directive 2001/20/EC, with the aim of decreasing the growing bureaucratization and stimulating clinical research in Europe, established simplified procedures, such as regulating a common procedure for authorising trials in Europe, the institution of strict assessment timelines, or the definition of new concepts, such as "low-intervention clinical trial". The legal form of a Regulation allowed the norm to be directly applied to Member States without the need for transposition. By means of the new Royal Decree, the national legislation is adapted to make the application of the regulation feasible and it allows the development of the aspects that the Regulation leaves to national legislation. Both documents seek to stimulate clinical research with medicinal products to foster knowledge, facilitate transparency, and reinforce subjects' safety. This will surely be the case, but with this revision, we will look at the novelties and key aspects that are most relevant to investigators and we will analyse the consequences for all parties involved in clinical research.

Diagnóstico y tratamiento del dolor irruptivo oncológico: recomendaciones de consenso / Diagnosis and treatment of breakthrought pain: consensus document

Introducción y objetivos: el dolor irruptivo oncológico (DIO) es una exacerbación aguda del dolor que presenta diferentes criterios diagnósticos y de tratamiento por parte de los distintos especialistas implicados en su manejo. Para facilitar la toma de decisiones en la práctica clínica habitual, ocho especialistas de referencia de cuatro sociedades científicas implicadas en el manejo del paciente oncológico handiseñado este documento. Métodos: tras una búsqueda bibliográfica en las publicaciones más relevantes sobre DIO se establecieron las recomendaciones preliminares. El grupo de expertos realizó una reunión de trabajo siguiendo la metodología Metaplan® en la que se debatieron las recomendaciones que incorporar al documento. Cada una de las afirmaciones y recomendaciones fueron clasificadas según su grado de recomendación, atendiendo a las categorías del sistema SIGN (Scottish Intercollegiate Guidelines Network). Resultados: el manejo del DIO requiere una anamnesis completa tanto del DIO como del dolor basal y una exploración física del paciente asociada a pruebas complementarias cuando sean precisas. Los fármacos de elección para el tratamiento del DIO deben ser aquellos que muestren una analgesia potente, con rápido inicio, de efectos secundarios mínimos y de fácil administración. El fentanilo administrado por vía transmucosa es actualmente el principio activo más adecuado a las necesidades analgésicas del dolor irruptivo, con independencia del opioide mayor utilizado para el control del dolor basal. Conclusión: este consenso puede ser una herramienta útil para la mejora de la calidad de vida del paciente con cáncer, ya que permite un mejor diagnóstico y tratamiento del DIO (AU)

Introduction and objectives: Breakthrough cancer pain (BTcP) is an acute exacerbation of baseline pain. The clinicians involved in its management have different diagnostic and therapeutic criteria. In order to facilitate decision making in usual clinical practice, 8 reference experts from 4 scientific associations involved in the management of patients with cancer pain have developed this Consensus Document. Methods: After an initial search on the most relevant publicationsin BTcP literature, a set of preliminary recommendations were established. A working meeting was subsequently held with the experts, following the Metaplan® methodology -a structured brainstorming technique- that produced a first version of theConsensus Document which, after several review rounds, was validated by all the participants. Every statement and recommendation was sorted according to its degree of recommendation, following the categories in the SIGN (Scottish IntercollegiateGuidelines Network) system. Results: The management of BTcP requires a full anamnesis, both of BTcP itself and of baseline pain, a physical examination and the supplementary tests that are deemed necessary. The drugs of choice for the treatment of BTcP must be those with a potent and rapid analgesic effect a short duration, minimal side effects and easy administration. Transmucosal fentanyl is currently the active ingredient most fitting to the analgesic needs of BTcP, regardless of the major opioid used for control of the baseline pain. Conclusion: This Consensus can be a very useful tool to improve the quality of life in cancer patients, because it guidesthe clinician towards a better diagnose and treatment of BTcP (AU)

Diagnóstico y tratamiento del dolor irruptivo oncológico: recomendaciones de consenso / No disponible

Introducción y objetivos: El dolor irruptivo oncológico (DIO) es una exacerbación aguda del dolor que presenta diferentes criterios diagnósticos y de tratamiento por parte de los diferentes especialistas implicados en su manejo. Para facilitar la toma de decisiones en la práctica clínica habitual, ocho especialistas de referencia de 4 sociedades científicas implicadas en el manejo del paciente oncológico, han diseñado este documento de consenso. Métodos: Tras una búsqueda bibliográfica en las publicaciones más relevantes sobre DIO, se establecieron las recomendaciones preliminares. El grupo de expertos realizó una reunión de trabajo siguiendo la metodología Metaplan®, donde se debatieron las recomendaciones a incorporar al documento. Cada una de las afirmaciones y recomendaciones fueron clasificadas según su grado de recomendación, atendiendo a las categorías del sistema SIGN (Scottish Intercollegiate Guidelines Network). Resultados: El manejo del DIO requiere de una anamnesis completa, tanto del DIO como del dolor basal, y una exploración física del paciente asociada a pruebas complementarias cuando sean precisas. Los fármacos de elección para el tratamiento del DIO deben ser aquellos que muestren una analgesia potente, con rápido inicio de acción, efectos secundarios mínimos y de fácil administración. El fentanilo administrado por vía transmucosa es actualmente el principio activo más adecuado a las necesidades analgésicas del dolor irruptivo, con independencia del opioide mayor utilizado para el control del dolor basal. Conclusión: Este consenso puede ser una herramienta útil para la mejora de la calidad de vida del paciente con cáncer, ya que permite un mejor diagnóstico y tratamiento del DIO (AU)

Introduction objectives: Breakthrough cancer pain (BTcP) is an acute exacerbation of baseline pain. The clinicians involved n its management have different diagnostic and therapeutic criteria. In order to facilitate decision making in usual clinical practice, 8 reference experts from 4 scientific associations involved in the management of patients with cancer pain have developed this Consensus Document. Methods: After an initial search on the most relevant publications in BTcP literature, a set of preliminary recommendations were established. A working meeting was subsequently held with the experts, following the Metaplan® methodology –a structured brainstorming technique– that produced a first version of the Consensus Document which, after several review rounds, was validated by all the participants. Every statement and recommendation was sorted according to its degree of recommendation, following the categories in the SIGN (Scottish Intercollegiate Guidelines Network) system. Outcomes: The management of BTcP requires a full anamnesis, both of BTcP itself and of baseline pain, a physical examination and the supplementary tests that are deemed necessary. The drugs of choice for the treatment of BTcP must be those with a potent and rapid analgesic effect a short duration, minimal side effects and easy administration. Transmucosal fentanyl is currently the active ingredient most fitting to the analgesic needs of BTcP, regardless of the major opioid used for control of the baseline pain (AU)

Professional survey on knowledge and clinical patterns of pain management in Spanish medical oncology

Cancer pain is still not treated adequately. The barriers impeding its appropriate treatment include lack of knowledge, erroneous beliefs and inappropriate attitudes with regard to pain, which are sustained by some or all of those involved in the problem. The present study shows the results of an exploratory survey using a large sample of specialists in clinical oncology. Its main objective is to evaluate daily analgesic practices and compliance with clinical guidelines in order to identify areas that should be improved in this particular therapeutic field. Information collection from the responders was in the form of a self-administered written questionnaire, structured in three thematic areas: clinical patterns and resources used in pain treatment in clinical practice, pain and pain-relief therapy, and theoretical knowledge and decision-making in clinical practice. The study identified those skills that most need improvement in the treatment of pain (scientific and technical knowledge and clinical decision-making capacity of professionals) in order to reduce the unjustified variability in current clinical practice (AU)

Recommendation of the scientific societies on the treatment of anaemia in cancer patients.

At present, anaemia in the patients with cancer remains a problem of the first magnitude and of increasing interest due to the high incidence, the major knowledge of its physiopathology, the negative impact on the quality of life of the patient, the influence on the evolution of the disease and its treatments and, finally to the progressive development of new alternatives of treatment, especially the erythropoietic agents. For all this, it becomes necessary to consider the treatment of the anemia of the patients with cancer as a basic part of their support treatment. The erythropoietic agents have demonstrated in the last years that constitute a therapeutic alternative to obtain an increase of the levels of hemoglobin in the patients with anticancer treatments, considering specially that the correction of the anemia not only represents the improvement of an analytical value but also has a significant impact on the quality of life of the patients and diminishes the transfusion requirements. Erythropoietic proteins available for the treatment of the anemia of the patients with cancer are Epoetin-alpha, Epoetin-beta and Darbepoetin-alpha. The existence of different drugs, different doses and intervals of administration, clinical different situations and heterogeneous studies, made necessary the development of documents of consensus and guides of clinical recommendations which provide information on the scientific evidence that supports the use of these agents in medical care. This paper summarizes the main recommendations from panels of experts and scientific societies published so far.

Adjuvant endocrine therapies for premenopausal women.

Adjuvant endocrine treatment for premenopausal woman remains a controversial area in the therapeutical approach of early stages of breast cancer. Metaanalysis show that ovarian ablation and suppression produce, in a global way, significant benefits in terms of reduction of the risk of recurrence and death. Nevertheless, in the presence of adjuvant chemotherapy, the benefits of ovarian suppression or ablation are clearly reduced, probably in relation to the impact that amenorrhoea induced by chemotherapy. On the other hand, in premenopausal patients, the same metaanalysis show that the use of adjuvant tamoxifen produces benefits in disease- free survival and overall survival very similar to those observed in postmenopausal women. Additionally, the benefits from tamoxifen persist independently of whether or not adjuvant chemotherapy is being received. Thus, some of the questions to answer are: first, is there, in premenopausal women, an additional benefit when ovarian suppression is associated to tamoxifen? Second, it remains controversial if ovarian suppression must be indicated for all patients who receive chemotherapy or only those that have not reached amenorrhoea when adjuvant chemotherapy is completed. Moreover, although in the last decades more than 15,000 premenopausal patients have been included in specific trials of adjuvant endocrine therapy with ovarian suppression or ablation, the best modality of treatment has not been established, and what is more important, the role of its association with tamoxifen has not been completely defined. Many of these aspects remain controversial and the decision about the best therapeutical approach must be individualised in each patient.

Adjuvant endocrine therapies for premenopausal women

Adjuvant endocrine treatment for premenopausal woman remains a controversial area in the therapeutical approach of early stages of breast cancer. Metaanalysis show that ovarian ablation and suppression produce, in a global way, significant benefits in terms of reduction of the risk of recurrence and death. Nevertheless, in the presence of adjuvant chemotherapy, the benefits of ovarian suppression or ablation are clearly reduced, probably in relation to the impact that amenorrhoea induced by chemotherapy. On the other hand, in premenopausal patients, the same metaanalysis show that the use of adjuvant tamoxifen produces benefits in disease- free survival and overall survival very similar to those observed in postmenopausal women. Additionally, the benefits from tamoxifen persist independently of whether or not adjuvant chemotherapy is being received. Thus, some of the questions to answer are: first, is there, in premenopausal women, an additional benefit when ovarian suppression is associated to tamoxifen? Second, it remains controversial if ovarian suppression must be indicated for all patients who receive chemotherapy or only those that have not reached amenorrhoea when adjuvant chemotherapy is completed. Moreover, although in the last decades more than 15,000 premenopausal patients have been included in specific trials of adjuvant endocrine therapy with ovarian suppression or ablation, the best modality of treatment has not been established, and what is more important, the role of its association with tamoxifen has not been completely defined. Many of these aspects remain controversial and the decision about the best therapeutical approach must be individualised in each patient (AU)

[Radiotherapy alone versus neo-adjuvant chemotherapy and irradiation in the treatment of carcinoma of the cavum]. / Radioterapia exclusiva frente a quimioterapia neoadyuvante más radioterapia en el tratamiento de los carcinomas de cávum.

Radiation therapy is the usual treatment for nasopharyngeal carcinoma. However, in recent years the use of neoadyuvant chemotherapy in the treatment of local and regionally advanced carcinoma has been investigated. We report the results of a retrospective study of two treatments used in our center. The study included 68 patients: 34 (group A) who received radiotherapy alone and 34 (group B) who received neoadyuvant chemotherapy before radiotherapy. In group A, 70.6% achieved a complete clinical response: 23.5% relapsed: 5 patients presented distant metastases. Survival rates at 5 and 10 years were 53% and 27% respectively; the disease-free survival was 71.4% at 5 years and 54% at 10 years. In group B, the complete clinical response rate to neoadyuvant chemotherapy was 35.3%, which increased to 73.5% when the treatment was complemented with radiotherapy. The relapse rate was 14.7%; the survival rates at 5 and 10 years were 49.5% and 49%, respectively; and the disease-free survival was 77.2% at 5 and 10 years.

[Importance of the early diagnosis of malignant neuroleptic syndrome: report of 2 cases]. / Importancia del diagnóstico precoz del síndrome neuroléptico maligno a propósito de dos casos.

Two cases of neuroleptic malignant syndrome presented in a psychiatry inpatient unit are commented, as well as their positive evolution.