Association of Performance Status and Pain in Metastatic Bone Pain Management in the Spanish Clinical Setting.

INTRODUCTION: Bone metastasis is the most common cause of cancer-related pain, and metastatic bone pain (MBP) is not only severe but also progressive in many patients. The aim of this study was to investigate the association between pain management and performance status in patients with metastatic bone cancer in the Spanish clinical setting. METHODS: A 3-month follow-up prospective, epidemiologic, multicenter study was conducted in 579 patients to assess the evolution of their performance, the impact of pain control on sleep and functionality, and the degree of pain control according to analgesic treatment. RESULTS: In patients with MBP, Eastern Cooperative Oncology Group (ECOG) status (1.5 ± 0.7-1.3 ± 0.7 and 1.3 ± 0.8; p < 0.001) and pain (6.5 ± 1.4-2.8 ± 1.9 and 2.1 ± 1.9; p < 0.001) improved significantly from baseline to months 1 and 3, as did functionality and sleep, after a treatment change consisting of increasing the administration of opioids. Evolution of ECOG and pain were closely related. ECOG and pain outcomes were significantly more favorable in patients treated with opioids versus non-opioid treatment, and in patients who did not need rescue medication versus those who did. CONCLUSIONS: MBP is currently poorly managed in Spain. ECOG improvement is closely and directly related to pain management in MBP. Opioid treatment and a lack of requirements for rescue medication are associated with better ECOG and pain outcomes in MBP patients. FUNDING: Mundipharma Pharmaceuticals S.L.

[Current status of EGFR/ErbB inhibitors in non-small cell lung carcinoma]. / Contexto actual de los inhibidores de EGFR/ErbB en carcinoma de pulmón no microcítico.

In the last 10 years, there has been a major change in the treatment of lung cancer (LC). The discovery of activating mutations in the epidermal growth factor receptor (EGFR) in some histological subtypes of LC and its sensitivity to tyrosine kinase inhibitors (TKI) has represented a substantial advance in the treatment of this entity. Until then, the only available option to treat this type of tumour was based on chemotherapy, with a small but significant benefit in terms of survival and quality of life. The arrival of new agents that act against activating EGFR mutations gave rise to the era of precision medicine with targeted therapies able to act on the origin of the tumour, thus providing a therapeutic benefit while minimizing adverse effects and delaying administration of chemotherapy. In addition, this has produced a change in the diagnostic paradigm of lung cancer (as well as in that of all tumours), with a shift from a purely histological diagnosis to a classification of tumours based on their mutational characteristics. This shift has been made possible by the development of technologies allowing complex DNA analysis. Together with the efforts of researchers from all over the world, these techniques allow continued discovery of genetic alterations that could be the target of new drugs as well as definition of the mechanisms of activity and resistance to treatments. This extraordinary development of targeted therapies cannot change the fact that metastatic lung cancer continues to be an incurable disease and, at the present time, only a few patients will benefit from targeted therapies. Ongoing research will shed new light on the molecular alterations that give rise to LC and will provide new treatment alternatives for this disease.

Contexto actual de los inhibidores de EGFR/ErbB en carcinoma de pulmón no microcítico / Current status of EGFR/ErbB inhibitors in non-small cell lung carcinoma

Durante los últimos 10 años hemos asistido a un cambio importante en el tratamiento del cáncer de pulmón. El descubrimiento en 2004 de las mutaciones activadoras del receptor del factor de crecimiento epidérmico (EGFR) en alguno de los subgrupos histológicos del cáncer de pulmón y su sensibilidad frente a los inhibidores de la tirosincinasa, ha supuesto un avance importante en el tratamiento del cáncer de pulmón. Hasta este momento, la única opción disponible para tratar este tipo de tumores se basaba en la quimioterapia, con un impacto beneficioso limitado pero significativo, tanto en la supervivencia como en la calidad de vida de los pacientes. La llegada de estos nuevos agentes dirigidos frente a las mutaciones activadoras del EGFR dio comienzo a la era de la «medicina de precisión», con terapias dirigidas capaces de actuar en el origen del tumor, permitiendo asegurar un beneficio terapéutico minimizando los efectos adversos y retrasando la administración de quimioterapia. Asimismo, esto ha producido un cambio en el paradigma diagnóstico del cáncer de pulmón (y también de todos los tumores) y se ha pasado de un diagnóstico meramente histológico a una clasificación de los tumores en función de sus características mutacionales. Esto ha sido posible gracias al desarrollo tecnológico, que permite realizar complejos análisis del ADN. Estas técnicas, junto con el esfuerzo conjunto de investigadores de todo el mundo, permiten seguir descubriendo alteraciones genéticas que pueden ser diana de nuevos medicamentos, así como definir los mecanismos de actividad y de resistencia a los tratamientos. Este desarrollo extraordinario de los tratamientos dirigidos no puede cambiar el hecho de que el cáncer de pulmón metastásico sigue siendo una enfermedad incurable y aún son pocos los pacientes que se benefician de estos tratamientos dirigidos. Las investigaciones que se siguen realizando permitirán continuar conociendo las alteraciones moleculares que dan origen al cáncer de pulmón y nos ofrecerán nuevas alternativas de tratamiento para esta enfermedad (AU)

In the last 10 years, there has been a major change in the treatment of lung cancer (LC). The discovery of activating mutations in the epidermal growth factor receptor (EGFR) in some histological subtypes of LC and its sensitivity to tyrosine kinase inhibitors (TKI) has represented a substantial advance in the treatment of this entity. Until then, the only available option to treat this type of tumour was based on chemotherapy, with a small but significant benefit in terms of survival and quality of life. The arrival of new agents that act against activating EGFR mutations gave rise to the era of precision medicine with targeted therapies able to act on the origin of the tumour, thus providing a therapeutic benefit while minimizing adverse effects and delaying administration of chemotherapy. In addition, this has produced a change in the diagnostic paradigm of lung cancer (as well as in that of all tumours), with a shift from a purely histological diagnosis to a classification of tumours based on their mutational characteristics. This shift has been made possible by the development of technologies allowing complex DNA analysis. Together with the efforts of researchers from all over the world, these techniques allow continued discovery of genetic alterations that could be the target of new drugs as well as definition of the mechanisms of activity and resistance to treatments. This extraordinary development of targeted therapies cannot change the fact that metastatic lung cancer continues to be an incurable disease and, at the present time, only a few patients will benefit from targeted therapies. Ongoing research will shed new light on the molecular alterations that give rise to LC and will provide new treatment alternatives for this disease (AU)

Reduced folate carrier (RFC) as a predictive marker for response to pemetrexed in advanced non-small cell lung cancer (NSCLC).

INTRODUCTION: RFC is the major transport system in mammalian cells for folate cofactors and antifolate therapeutics. The aim of this study was to assess the predictive value of RFC expression in patients receiving pemetrexed for advanced NSCLC. METHODS: The study was carried out in a population of 48 patients with advanced NSCLC which have received pemetrexed monotherapy in second and third line. RFC expression was assessed using a two-step model of immunohistochemical staining in paraffin-embedded tissue samples. RESULTS: RFC expression was detected in 16 (33 %) patients. In the global population, the median progression free survival (PFS) and the median overall survival (OS) were 3.3 and 6.5 months respectively. The subgroup of patients with expression of RFC had a tendency to better median PFS (4.5 vs 2.8 months; p = 0.926) and median OS (11.7 vs 4.8; p = 0.150). In patients with adenocarcinoma histology and RFC expression median OS after treatment with pemetrexed was 14.4 months versus 5.0 in those with adenocarcinoma but without RFC expression (p = 0.039). CONCLUSIONS: These results suggest the possible relation between RFC expression and response to treatment with antifolates (pemetrexed) independently of the tumor histology. Further studies are required to confirm these results.

Oral vinorelbine: role in the management of metastatic breast cancer.

The treatment of advanced breast cancer is continually evolving, with the aim of improving the quality and duration of remission and, in some instances, survival. In this setting, the importance of quality of life cannot be underestimated, and growing attention is being paid to treatment convenience and compliance. New anticancer agents have improved efficacy, but for many of them, toxicity often remains a problem. Vinorelbine seems to represent both an active and a well tolerated treatment for metastatic breast cancer. In particular, the oral formulation has similar efficacy to that of the injectable formulation and has demonstrated generally favourable tolerability, with a high degree of acceptance by both patients and physicians. The availability of this and other novel, well tolerated and effective treatments provides greater potential to tailor treatment to meet individual patient needs and, therefore, also provide the potential to improve patient outcomes. Preliminary data suggest that oral vinorelbine may permit continued, effective chemotherapy when further parenteral therapy with more intensive and more toxic agents is considered inappropriate. Early findings also suggest that oral vinorelbine, when administered together with another new oral agent, capecitabine, may be a valid choice in metastatic breast cancer treatment. Furthermore, vinorelbine plus the monoclonal antibody trastuzumab, with or without oral capecitabine, appears to be another regimen that may be worthy of additional study in patients with human epidermal growth factor-2 positive advanced breast cancer.

Retrospective review in patients with pulmonary metastases of renal cell carcinoma receiving inhaled recombinant interleukin-2.

Pulmonary metastases of renal cell carcinoma are associated with poor prognosis. Systemic interleukin-2 is used to treat pulmonary metastases of renal cell carcinoma; however, its toxicity limits its use. The objective of this study was to evaluate the efficacy and safety of inhaled interleukin-2 in pulmonary metastases of renal cell carcinoma patients. The study was designed as a retrospective chart review in pulmonary metastases of renal cell carcinoma patients treated with inhaled interleukin-2. Between 2000 and 2004, 19 centres in Spain and two in Portugal recruited 51 patients. The treatment schedule was as follows: three cycles of 36 MIU interleukin-2 per day for 5 days/week for 12 weeks (with 1 treatment-free week between cycles) in Spain and for 3 weeks (out of each 4 weeks) for 12 weeks in Portugal. Efficacy was assessed by best response following each treatment cycle and at final evaluation. Kaplan-Meier method was used to estimate progression-free survival and overall survival. Safety data were analysed using descriptive statistics, with toxicities expressed in number of weeks, which were reported. Overall objective response rate was 13.7% (95% confidence interval: 5.7-26.3). Median progression-free survival and overall survival were 8.6 (95% confidence interval: 3.45-16.5) and 23 (95% confidence interval: 11.5-34.5) months. The most common toxicities were cough (40% of cycles) and fatigue (7%). The majority of weeks of toxicities were reported to be only grade 1 or 2 in severity. Inhaled interleukin-2 shows efficacy and mild toxicity of pulmonary metastases of renal cell carcinoma patients, and might be considered as an alternative treatment to the systemic administration of this drug in these patients.

Activity of carboplatin in patients with advanced non-small cell lung cancer pre-treated with a non-platinum combination.

To assess the efficacy of carboplatin when used as a single agent in patients with advanced non small cell lung cancer (NSCLC) and who are refractory to chemotherapy with a non-platinum combination, we recruited patients (n=40) NSCLC patients, 36 of whom were males, with an overall median age of 59 years (range 39-79) and Karnofsky Performance Status of 70% (range 60-90%). At baseline, the patients had a median of one disease site (range 1-3) and had received a median of one prior regimen (range 1-2). Carboplatin was administered (i.v.; AUC=6) every 3 weeks until disease progression or non-acceptable toxicity was reached. In total 169 cycles were administered (median 4 cycles/patient; range 1-8). Main toxicities were grade 2-3 anemia and grade 4 thrombocytopenia (22.5% of patients). Overall clinical response rate was 10% (4 partial responses); 26 patients (65%) had stable disease and 8 (20%) had disease progression. Median time to progression and median survival time were 90 and 187 days, respectively. One year survival rate was 13%. We conclude that carboplatin shows minimal toxicity with a discrete anti-tumor activity in patients with NSCLC and who are refractory to non-platinum combinations.