Breakthrough cancer pain: review and calls to action to improve its management.

In this paper, we review the current state of breakthrough cancer pain (BTcP) management. BTcP is a heterogeneous condition and a global problem for cancer patients. It is often managed suboptimally, which results in a negative outcome for patients, healthcare providers, and healthcare systems. Several barriers to the appropriate management of BTcP have been identified. These include, among others, an incomplete definition of BTcP, poor training of healthcare providers and patients alike, a lack of a multidisciplinary approach and the absence of specific protocols and tools. We provide some actions to help physicians and patients improve their approach to BTcP, including specific training, the design of easy-to-use tools for BTcP identification and assessment (such as checklists and pocket-sized cards), individualized treatment, and the use of multidisciplinary teams.

HLA-G as a new tumor biomarker: detection of soluble isoforms of HLA-G in the serum and saliva of patients with colorectal cancer.

INTRODUCTION: Recent medical investigations suggest that HLA-G, due to its tolerogenic properties, can be used as a biomarker in the diagnosis, treatment, and prognosis of different neoplasms. This observational prospective pilot study aims at detecting sHLA-G in the serum and saliva of patients diagnosed with colorectal cancer (CRC). For this purpose, we compared the expression of sHLA-G from patients with a control sample from a healthy population. MATERIALS AND METHODS: Using the specific enzyme-linked immunosorbent assay (ELISA) method, the expression of sHLA-G in the serum and saliva samples from patients affected by CRC (n = 20) and in a control sample (n = 10) were analyzed. RESULTS: The data showed that in patients with CRC, salivary sHLA-G values were significantly higher than in the control group (18.84 U/ml versus 6.3 U/ml, p = 0.036). In addition, higher levels of sHLA-G were observed in the saliva of patients with CRC in more advanced stages, compared with patients in early stages (24.2 U/ml vs. 8.1 U/ml, p = 0.019). A significant correlation was observed between the concentration of sHLA-G in the serum and saliva of the analyzed samples (Spearman correlation 0.7, p = 0.004). CONCLUSIONS: This study demonstrates, for the first time, the possibility of detecting sHLA-G in the saliva of patients with CRC, resulting in a less invasive alternative to venipuncture. Likewise, we propose that sHLA-G could be an attractive molecular target based on its significant high levels in advanced stages.

Effectiveness of daily versus non-daily granulocyte colony-stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice.

We conducted a multicentre, retrospective, observational study including patients with solid tumours (excluding breast cancer) that received granulocyte colony-stimulating factors (G-CSF) and chemotherapy. We investigated the effectiveness of daily vs. non-daily G-CSFs (pegfilgrastim) adjusting by potential confounders. The study included 391 patients (211 daily G-CSF; 180 pegfilgrastim), from whom 47.3% received primary prophylaxis (PP) (57.8% pegfilgrastim), 26.3% secondary prophylaxis (SP: initiation after cycle 1 and no reactive treatment in any cycle) (51.5% pegfilgrastim) and 26.3% reactive treatment (19.4% pegfilgrastim). Only 42.2% of patients with daily G-CSF and 46.2% with pegfilgrastim initiated prophylaxis within 72 h after chemotherapy, and only 10.5% of patients with daily G-CSF received it for ≥ 7 days. In the multivariate models, daily G-CSF was associated with higher risk of grade 3-4 neutropenia (G3-4N) vs. pegfilgrastim [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.004-2.97]. Relative to SP, PP protected against G3-4N (OR for SP vs. PP: 6.0, 95%CI: 3.2-11.4) and febrile neutropenia (OR: 3.1, 95%CI: 1.1-8.8), and was associated to less chemotherapy dose delays and reductions (OR for relative dose intensity <85% for SP vs. PP: 3.1, 95%CI: 1.7-5.4) and higher response rate (OR: 2.1, 95%CI: 1.2-3.7). Data suggest that pegfilgrastim, compared with a daily G-CSF, and PP, compared with SP, could be more effective in preventing neutropenia and its related events in the clinical practice.

Eficacia de la intervención mediante automedición de la presión arterial en el control de la hipertensión arterial / Efficacy of the intervention by self-measurement of blood pressure in arterial hypertension control

Introducción. Estudiar en condiciones de práctica clínica habitual el efecto de la automedición domiciliaria (AMPA) sobre el descenso de presión arterial (PA) en hipertensos. Material y métodos. Estudio experimental en Atención Primaria. Participaron 109 pacientes con hipertensión arterial (HTA) ligera, mal controlados en consulta, aleatorizados en grupo intervención (GI), que fue instruido para la AMPA, facilitándosele un automedidor electrónico validado, y grupo control (GC) que siguió el programa de HTA del área. Se controlaron sus PA con una monitorización ambulatoria de la presión arterial (MAPA), al inicio, 18 y 30 meses. Se consideró controlada la PA con media por MAPA de 24 horas menor de 130/80 mmHg. Se registró el consumo de fármacos por dosis diaria definida, el índice de bienestar psicológico y las visitas por HTA y totales al Centro de Salud y otras variables demográficas y factores de riesgo cardiovascular. Se realizó análisis bivariante y multivariante por regresión lineal múltiple y/o regresión logística. Resultados. El descenso de la PA fue similar en ambos grupos, con tendencia a ser menor en el GI que en el GC a los 30 meses (diferencia de 3,6 mmHg para la PA sistólica y 2,3 mmHg la diastólica en el MAPA de 24 horas; "p", respectivamente, de 0,036 y 0,052) a expensas de la presión nocturna, no habiendo diferencias significativas en la diurna. No hay diferencias significativas en el control de la PA. El GI consume menos fármacos (1,1 frente a 1,3; p = 0,010). Discusión. Constatamos un menor descenso de la PA en el grupo de AMPA, en cifras moderadas, a expensas de la presión nocturna. El impacto sobre el proceso asistencial es favorable con un menor consumo de fármacos

Introduction. Study the effect of home self-measurement (HSM) on decrease in blood pressure (BP) in hypertensive subjects under usual clinical practice conditions. Material and methods. Experimental study in Primary Health Care. A total of 109 patients with mild hypertension poorly controlled in the consultation, participated. They were randomized into intervention group (IG), that was instructed on the use of HSM, providing them with a validated electronic self-measurer, and the control group (CG) who followed the area hypertension program. Blood pressure (BP) was measured with ambulatory blood pressure monitoring (ABPM), at onset, 18 and 30 months. BP was considered to be controlled by ABPM with a mean of 24 hours less than 130/80 mmHg. Drug consumption was recorded by daily defined dose, psychological wellbeing index and visits due to hypertension and total visits to the Health Center and other demographic variables and cardiovascular risk factors. Bivariate and multivariate analysis were performed by multiple linear regression and/or logistic regression. Results. Decrease of BP was similar in both groups, with tendency to be less in the IG than in the CG at 30 months (difference of 3.6 mmHg for systolic BP and 2.3 mmHg for diastolic in the 24 hour ABPM, "p" respectively of 0.036 and 0.052) at expense of nocturnal pressure. There were no significant difference in the daytime pressure. There were no significant differences in the BP control. IG consumed fewer drugs (1.1 vs 1.3; p = 0.010). Discussion. We observe less BP decrease in the ABPM group, in moderate values, at expense of nocturnal pressure. The impact of the health care process is favorable with less drug usage

Utilidad de la automedida de la presión arterial en el control del paciente hipertenso / Usefulness of self-measurement of blood pressure in the control o hypertension

Objetivo. La automedida de la presión arterial (AMPA) ha sido estudiada como método de diagnóstico y verificación del control del hipertenso, pero muchos hipertensos la utilizan a menudo sin indicación médica como control habitual. Nos proponemos estudiar la utilidad de un programa de automedida para el control de un grupo de hipertensos comparándolo con el control habitual en la consulta. Mediciones y resultados. Realizamos un estudio experimental en Atención Primaria. Se incluyeron 109 pacientes, 52 en el grupo de intervención (GI), que fue instruido para la automedida, entregándosele a cada paciente un monitor validado y calibrado, y 57 en el de control. Se realizó una monitorización ambulatoria de presión arterial (MAPA) de 24 horas al comienzo y a los 6 meses, y se midieron otros factores de riesgo cardiovascular, el consumo de fármacos antihipertensivos y el índice de bienestar psicológico. El 59 per cent fueron mujeres y el 41 per cent hombres, con una edad media de 58,38 años. Las medias de las presiones arterial sistólica y diastólica de la monitorización total y diurna han descendido a los 6 meses, pero no se detectan diferencias significativas entre los grupos. El consumo de fármacos es menor en el GI, y mayor su bienestar psicológico, sin que estas diferencias alcancen significación ni a nivel bivariante ni multivariante. La pertenencia al grupo intervención o control no se asocia de forma significativa con el descenso de la presión arterial. Conclusiones. El control de la hipertensión mediante un programa de automedida como el estudiado no difiere del alcanzado con la atención ordinaria en consulta. Estudios posteriores deberán constatar si la tendencia apreciada a los 6 meses hacia un mayor bienestar y menor consumo de fármacos se confirma (AU)

Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC).

BACKGROUND: There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC. PATIENTS AND METHODS: Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was > or =70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m2 was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m2 on day 15 of each 28-day cycle. RESULTS: Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin. CONCLUSIONS: Gemcitabine can be safely administered at a dose of 1200 mg/m2 in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this studyshow promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study.

Modified weekly regimen with vinorelbine as a single agent in unresectable non-small cell lung cancer.

After a 26% response rate was reported with a 20/mg/m2/week vinorelbine (VRL) dose, a multicenter phase II trial of a modified weekly VRL treatment protocol (30 mg/m2 days 1 and 8 every 21 days) for unresectable non-small cell lung cancer (NSCLC) was designed to determine its clinical activity, toxicity, and survival of treated patients. As myelotoxicity frequently precludes the administration of VRL, by suppressing the dose that would correspond to day 15 of a weekly protocol, we allowed bone marrow recovery to take place and avoided the administration of the drug at the nadir of the cycle. The trial included 71 consecutive, previously untreated patients with unresectable and measurable disease. A total of 297 three-week treatment courses were administered with an average of 4 courses per patient (range 1-11). Results showed that in spite of attaining a median dose intensity of 19 mg/m2/week, this modified weekly VRL treatment regimen has a low level of activity (7.5% response rate) in NSCLC. Although a more tolerable level of toxicity is achieved, in order to maintain its antitumor activity, the recommended dose of VRL when given alone for NSCLC treatment (30 mg/m2/weekly) should not be decreased.