Chemotherapy at the end of life: up until when?

AIM: The aim of this study is to analyze the use of CT in terminal stage cancer and the percentage of patients who received UCPD in 2009 and 2010 on the Medical Oncology and Palliative Home Care integrated service (UCPD) ward of the Marqués de Valdecilla University Hospital. METHOD: Retrospective analysis of death rate registered on the Medical Oncology ward for 2009 and 2010 and the recorded date of the last CT given. The data are analyzed using the SPSS version 15.0 statistic package. Data were obtained from the Database Minimum Set for oncology admissions. RESULTS: The death rate on the Medical Oncology ward is 22-24%. Total number of cases studied is 303. 47% of patients are aged 60 or younger. 81.8% (248) received active cancer treatment; of these, 138 (55.6%) in the last month, and 84 (33.8%) in the last 2 weeks. Only 66 patients out of those who died on the ward (21%) were previously sent to the UCPD. CONCLUSIONS: Even when it is known that the majority of cancer patients become resistant to CT at the end of their lives, it is often given to patients of all ages. The request for palliative care is rare and often late.

Quimioterapia en la fase final de la vida: ¿es compasiva? / Chemotherapy at the end of life. Is it compassive?

No disponible

Spanish Society of Medical Oncology consensus on the use of erythropoietic stimulating agents in anaemic cancer patients.

Treatment of anaemia is a very important aspect in the management of cancer patients. In order to carry out a consensus process about the use of erythropoietic stimulating agents (ESAs) in cancer patients, the Spanish Society of Medical Oncology (SEOM) elaborated a working group which coordinated a panel of medical oncology specialists. This working group has reviewed the main issues about the use of ESAs. In addition a consensus meeting was held in Madrid on 25 April 2007. The following conclusions were made: Since ESA treatment increases the haemoglobin (Hb) level and decreases the red blood cell (RBC) transfusion requirements, ESAs should be used within the approved indications in patients undergoing chemotherapy treatment, beginning at a Hb level below 11 g/dl and maintaining it around 12 g/dl, with iron supplements if necessary. Neither increasing the ESA dose in nonresponders nor the use of ESAs in the treatment of chronic cancer-related anaemia is recommended.

Desasosiego o "disconfortabilidad": ¿un síntoma refractario en la fase final de la vida? / Uneasiness or uncomfortably: Is it a symptom ovenproof in the end of life?

No disponible

No disponible

Protein energy malnutrition (PEM) in cancer patients.

INTRODUCTION: Cancer patients show protein energy malnutrition (PEM) throughout the evolution of the disease. The main objective of this work is to find out the prevalence of PEM in the studied sample, as well as how to assess the nutritional state of patients. MATERIAL AND METHODS: Non-interventionist, longitudinal and prospective study. Cancer patients from 103 researchers (6 specialties) from 65 hospitals of 15 Spanish Autonomous Communities. Results 561 patients were included in the study. The mean age was 62.6 years and 68.8% were men. The average basal body mass index (BMI) was 22.1 kg/m2. In 18.2% the BMI was low; 21.6% were overweight, pre-obese or obese; 22.9% had a localised tumour and 77.1% had an advanced one, first and foremost located in the head and neck, digestive system and lungs. In 72.7% of cases, it was treated with chemotherapy (CT) and in 38.3% with CT and radiotherapy (RT). 96.4% had nutrition problems: 70.9% (398/561) had anorexia, 34.8% (195/561) gastrointestinal pro blems, 32.6% (183/561) dysgeusia, 40.5% (227/561) dysphagia and others 8.6% (48/561). Weight loss occurred in 90.7% (an average of 4.2 months). CONCLUSION: If we analyse the BMI of patients, it can be seen that 60.2% have an adequate weight according to their size against 17.3% of patients who are overweight or preobese, and the remaining 4.3% are obese. Only 18.2% of patients are underweight. Over 90% have suffered recent weight loss.

Predictors of response to erythropoiesis-stimulating agents (ESA) in cancer patients: the role of baseline serum epoetin level.

Anemia is the most frequent hematologic abnormality among cancer patients. Its pathophysiology comprises reduction in erythrocyte half-life, poor iron reutilization by the bone marrow, and inadequate response to erythropoietin (EPO), with reduced endogenous EPO (eEPO) levels. Current treatment implies the use of erythropoiesis- stimulating agents (ESA), to which 35-48% of patients show primary resistance. The search for predictors of response to ESA treatment has been inconclusive. Iron or vitamin deficiency, the recent need for transfusion, or a lack of hemoglobin increase within the first 2-4 weeks usually predict resistance to ESA. High serum eEPO levels at treatment initiation (>100-150 mU/ml) may also predict resistance, especially in hematologic malignancies, but the results in solid tumors are not consistent. Although patients with cancer-related anemia show higher eEPO levels than patients without anemia, there is extreme variability among individuals. Future studies are needed to clarify eEPO usefulness in predicting response to ESA treatment.

Retrospective analysis of surgical resection after induction chemotherapy for patients with T4b squamous cell head and neck cancer.

BACKGROUND: Standard treatment of patients with T4b squamous cell head and neck cancer (T4b-SCHNC) is concomitant chemo-radiotherapy (CT-RT). Recent Phase III trials with Taxane containing induction chemotherapy (IC) suggest that IC could also play a role in this setting. The value of resecting the residual mass after IC and before RT is not yet clear in this context. METHODS: We present the results of a retrospective analysis. RESULTS: Between 1984 and 2001, 113 patients (patients) with T4b-SCHNC were treated at our institution with IC. Four patients dead during IC and 57 patients achieved a complete or a >90% partial response at primary and proceeded to definitive RT (or concomitant CT/RT). Surgical resection was reconsidered after IC and before RT in the other 52 patients. Surgery was performed in 13 of them: in 7 patients resection was R1, all of them had loco-regional progression (2 also developed systemic metastases) and median OS after surgery was 21 months, with no patient alive at 48 months. In the other 6 patients a R0 resection was performed: 3 of these patients had loco-regional relapses (1 also developed systemic metastases) and the other 3 patients remain alive and disease free 56, 62 and 72 months after surgery. Considering the 52 patients that achieved less than a 90% partial response at primary with IC, overall survival was equivalent when no Resection or an R1 resection was performed after IC (5 year OS 8 vs. 0%, lrk, p=0.74), but a statistically significant improvement in OS was observed when an R0 resection was obtained (5 years OS 50%, lrk, p=0.02). CONCLUSIONS: R0 resections after IC and before RT could indicate an improvement in OS in patients with T4b-SCHNC that obtain less than a 90% PR at primary after IC. We consider that this approach deserves further research in prospective clinical trials.

Randomized phase II study of cisplatin and 5-FU continuous infusion (PF) versus cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy in locally advanced squamous cell head and neck cancer (LA-SCHNC).

OBJECTIVES: We conducted a multicentric randomized phase II trial comparing 5-FU continuous infusion (PF) and cisplatin, UFT and vinorelbine (UFTVP) as induction chemotherapy (IC) in locally advanced squamous cell head and neck cancer (LA-SCHNC). Primary objective was complete response (CR) to IC and overall survival (OS) was a secondary objective. MATERIALS AND METHODS: PF: cisplatin 100 mg/m(2) i.v. Day 1 (D1) and 5-FU 1,000 mg/m(2) per day i.v. continous infusion D1-D5, every 21 days. UFTVP: cisplatin 100 mg/m(2) i.v. D1; UFT 200 mg/m(2) per day p.o. D1-D21 and vinorelbine 25 mg/m(2) i.v. D1 and D8, every 21 days. Four IC courses were planned in both arms. RESULTS: A total of 206 patients (pts) were included (PF/UFTVP: 99/107): oral cavity: 8%/10%, oropharynx: 20%/25%, hypopharynx: 17%/14%, larynx: 54%/50%. Stage (TNM, 2002): III: 41%/35%, IVA: 23%/27%, IVB: 35%/38%. Complete response to IC: PF:36%/UFTVP:31% (P: no significative (NS)). G 3-4 toxicity (PF/UFTVP): neutropenia: 52%/72%; febrile neutropenia: 3%/20% (P < 0.001); anaemia:1%/14% (P < 0.001); trombocytopenia: 5%/0% (P = 0.02); mucositis: 15%/7% (P < 0.001). Deaths during IC: 2(2%)/3(3%). IC with UFTVP was associated with a favourable OS in the Cox analysis (actuarial 5 year OS: 49% vs. 34%; HR: 0.67, 95% CI: 0.47-0.95, P: 0.03). CONCLUSIONS: Although clinical response is equal in both arms, overall survival (Cox) is better in the UFTVP arm. Febrile neutropenia and anaemia were more frequent with UFTVP while mucositis and trombocytopenia were more severe with PF.

Long term results of a phase II trial of induction chemotherapy with uracil-ftegafur (UFT), vinorelbine and cisplatin (UFTVP) followed by radiotherapy concomitant with UFT and carboplatin (RT/UFTJ) in non-resectable locally advanced (stage IV-B) squamous cell head and neck carcinoma and peripheral blood stem cell support (PBSCS) with febrile neutropenia.

PURPOSE: To evaluate the response of advanced squamous cell head and neck carcinoma to a combination of induction chemotherapy and radiotherapy. METHODS: We present long-term results of a phase II trial of Induction Chemotherapy with UFT 200 mg/m(2) p.o. days 1 to 21, Vinorelbine 25 mg/m(2) i.v. days 1 and 8 and Cisplatin 100 mg/m(2) i.v. day 1 (UFTVP) each 21 days for 4 courses, followed by Radiotherapy concomitant with UFT 100 mg/m(2) p.o. daily and Carboplatin AUC = 0.5 i.v. weekly (RT/UFTJ) in patients (pts) with Non-Resectable Locally Advanced (Stage IV-B) Squamous Cell Head and Neck Carcinoma (IV-B-SCHNC). Primary endpoint was Complete Response to induction UFTVP and secondary endpoints were Disease Free Status Rate after locoregional treatment and long-term Overall Survival. Between 1994 and 1997, 32 pts were included. RESULTS: Complete Response to Induction UFTVP was 59% (95% CI: 48%-70%). Main toxicity of UFTVP was G 3,4 neutropenia (94% of pts; 25% developed febrile neutropenia and 1 of this pts dead). After Induction Chemotherapy with UFTVP, 30 pts received radiotherapy and 25 of them received concomitant Carboplatin and UFT (RT/UFTJ): main toxicity was mucositis (G3-4: 72%) and one patient died during RT/UFTJ because pneumonia. Twenty-five pts (78%) were alive and disease free at the end of the whole treatment. Actuarial 5 year Overall survival is 32%. CONCLUSION: Although toxicity is important, this approach has interesting activity and deserves further investigation.

Oncologists' perceptions of cancer pain management in Spain: the real and the ideal.

AIM: Studies in some countries suggest that cancer pain is often not adequately controlled, but little is known about the situation in Spain. The objective of this study was to identify medical oncologists' perceptions about pain management in their patients. METHODS: Two-round Delphi survey of 24 medical oncologists from 22 large, geographically diverse hospitals in Spain. Physicians rated each of 150 statements on a Likert scale (1=strongly disagree; 5=strongly agree). The mean, standard deviation and frequency of replies in three agreement categories were calculated for each item. Statements allowing comparison of oncologists' perceptions of how pain is managed in routine clinical practice with how it should be managed were grouped together and analyzed. RESULTS: The most notable discrepancies between the real and the ideal occurred in the failure to provide written information or to confirm that patients understand what they are told, the lack of comprehensive and systematic evaluation of pain, and the lack of use of non-pharmacological treatments (NPTs) for cancer pain. CONCLUSIONS: Medical oncologists need to improve their communication skills, providing patients with both written and verbal information about their disease and the plan for pain management. Pain should be evaluated at each patient visit using validated scales, and greater attention should be paid to the possible use of NPTs.

Informed consent and sedation.

The concept of autonomy was not included in the Hippocratic Oath. Nowadays the principle of respect for autonomy is an important right. The basic paradigm of autonomy in health-care, politics and other contexts is expressed as informed consent. In the palliative-care setting, there can be some difficulties in getting informed consent, especially at the end-of-life stage. Can it be good for the patient, always? Could there be some exceptions? At the time of agonizing pain, getting informed consent could become an additional burden for the patient. This present article attempts to shed light on this issue. In our experience, it is not necessary to obtain written consent for a patient who has already expressed his priorities in advance. We believe that this is a good stance for patients as well as doctors.

¿Es posible gestionar el proceso de morir? Voluntades anticipadas / Can we manage the dying process? Wills in advance

No disponible

Informed consent and sedation

No disponible

The concept of autonomy was not included in theHippocratic Oath. Nowadays the principle of respectfor autonomy is an important right. The basicparadigm of autonomy in health-care, politics andother contexts is expressed as informed consent. Inthe palliative-care setting, there can be some difficultiesin getting informed consent, especially at theend-of-life stage. Can it be good for the patient, always?Could there be some exceptions? At the timeof agonising pain, getting informed consent couldbecome an additional burden for the patient. Thispresent article attempts to shed light on this issue.In our experience, it is not necessary to obtain writtenconsent for a patient who has already expressedhis priorities in advance. We believe that this is agood stance for patients as well as doctors

El final de la última enfermedad / The end of the last disease

No disponible

Breast cancer cells can evade apoptosis-mediated selective killing by a novel small molecule inhibitor of Bcl-2.

Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-x(L), are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role in cancer cells. In vitro studies showed that YC137 inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an interaction essential for the antiapoptotic activity of Bcl-2. This inhibitor induces apoptosis of hematopoietic progenitors overexpressing Bcl-2 but not Bcl-x(L) and breast cancer cells that express high levels of Bcl-2. On the contrary, a variety of normal primary cells, including CD34(+) progenitors, myoblasts, and peripheral blood mononuclear cells, do not respond to the inhibitor. A breast cancer cell line resistant to YC137 was generated. Analysis of resistant cells revealed a reduced expression of Bcl-2, which correlated with low activation of signal transducer and activator of transcription-3 (Stat3) and reduced expression of the human epidermal growth factor receptor-2 (HER2). Of note, YC137-resistant cells were more sensitive to apoptosis induced by chemotherapy. Because HER2 has not been linked previously to the Stat3-Bcl-2 transcriptional pathway, we additionally confirmed that specific blockade of HER2 in breast cancer cells resulted in down-regulation of Stat3 activity and reduced levels of Bcl-2. Consistently, HER2 blockade led to YC137 resistance. These data provide evidence for the selective killing of tumor cells by YC137 and represent the first example of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor.