A Signal-finding Study of Abemaciclib in Heavily Pretreated Patients with Metastatic Castration-Resistant Prostate Cancer: Results from CYCLONE 1.

BACKGROUND: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors radically changed the treatment paradigm for breast cancer. Similar to estrogen receptor in breast cancer, androgen receptor signaling activates cyclin D-CDK4/6, driving proliferation and resistance to hormonal manipulation in prostate cancer. This study was designed to detect signals of clinical activity for abemaciclib in treatment-refractory metastatic castration-resistant prostate cancer (mCRPC). METHODS: Eligible patients had progressive mCRPC, measurable disease, and previously received ≥1 novel hormonal agent(s) and 2 lines of taxane chemotherapy. Abemaciclib 200 mg BID was administered on a continuous dosing schedule. Primary endpoint was objective response rate (ORR) without concurrent bone progression. This study was designed to detect a minimum ORR of 12.5%. RESULTS: At trial entry, forty (90.9%) of 44 patients had objective radiographic disease progression, four (9.1%) had prostate-specific antigen (PSA)-only progression, and 20 (46.5%) had visceral metastases (of these, 60% had liver metastases). Efficacy analyses are as follows: ORR without concurrent bone progression: 6.8%; disease control rate: 45.5%; median time to PSA progression: 6.5 months (95% CI: 3.2, NA); median radiographic PFS; 2.7 months (95% CI: 1.9, 3.7); and median OS: 8.4 months (95% CI: 5.6, 12.7). Most frequent grade ≥3 TEAEs were neutropenia (25.0%), anemia, and fatigue (11.4% each). No grade 4 or 5 AEs were related to abemaciclib. CONCLUSION: Abemaciclib monotherapy was well tolerated and showed clinical activity in this heavily pretreated population, nearly half with visceral metastases. This study is considered preliminary proof-of-concept and designates CDK4/6 as a valid therapeutic target in prostate cancer.

SEOM SOGUG clinical guideline for treatment of kidney cancer (2022)

Renal cancer is the seventh most common cancer in men and the tenth in women. The aim of this article is to review the diagnosis, treatment, and follow-up of renal carcinoma accompanied by recommendations with new evidence and treatment algorithms. A new pathologic classification of RCC by the World Health Organization (WHO) was published in 2022 and this classification would be considered a “bridge” to a future molecular classification. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. Adjuvant treatment with pembrolizumab is an option for intermediate-or high-risk cases, as well as patients after complete resection of metastatic disease. More data are needed in the future, including positive overall survival data. Clinical prognostic classification, preferably IMDC, should be used for treatment decision making in mRCC. Cytoreductive nephrectomy should not be deemed mandatory in individuals with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Metastasectomy can be contemplated in selected subjects with a limited number of metastases or long metachronous disease-free interval. For the population of patients with metastatic ccRCC as a whole, the combination of pembrolizumab–axitinib, nivolumab–cabozantinib, or pembrolizumab–lenvatinib can be considered as the first option based on the benefit obtained in OS versus sunitinib. In cases that have an intermediate IMDC and poor prognosis, the combination of ipilimumab and nivolumab has demonstrated superior OS compared to sunitinib. As for individuals with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab and cabozantinib are the options of choice. When there is progression following initial immunotherapy-based treatment, we recommend treatment with an antiangiogenic tyrosine-kinase inhibitor (AU)

SEOM SOGUG clinical guideline for treatment of kidney cancer (2022).

Renal cancer is the seventh most common cancer in men and the tenth in women. The aim of this article is to review the diagnosis, treatment, and follow-up of renal carcinoma accompanied by recommendations with new evidence and treatment algorithms. A new pathologic classification of RCC by the World Health Organization (WHO) was published in 2022 and this classification would be considered a "bridge" to a future molecular classification. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. Adjuvant treatment with pembrolizumab is an option for intermediate-or high-risk cases, as well as patients after complete resection of metastatic disease. More data are needed in the future, including positive overall survival data. Clinical prognostic classification, preferably IMDC, should be used for treatment decision making in mRCC. Cytoreductive nephrectomy should not be deemed mandatory in individuals with intermediate-poor IMDC/MSKCC risk who require systemic therapy. Metastasectomy can be contemplated in selected subjects with a limited number of metastases or long metachronous disease-free interval. For the population of patients with metastatic ccRCC as a whole, the combination of pembrolizumab-axitinib, nivolumab-cabozantinib, or pembrolizumab-lenvatinib can be considered as the first option based on the benefit obtained in OS versus sunitinib. In cases that have an intermediate IMDC and poor prognosis, the combination of ipilimumab and nivolumab has demonstrated superior OS compared to sunitinib. As for individuals with advanced RCC previously treated with one or two antiangiogenic tyrosine-kinase inhibitors, nivolumab and cabozantinib are the options of choice. When there is progression following initial immunotherapy-based treatment, we recommend treatment with an antiangiogenic tyrosine-kinase inhibitor. While no clear sequence can be advocated, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in the setting of metastatic RC.

The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalizing the measurement of albuminuria to identify vascular risk and prevent vascular disease.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Determinants of poor clinical outcome in patients with influenza pneumonia: A systematic review and meta-analysis.

BACKGROUND: The clinical burden of influenza is increasing worldwide. Aging, immunosuppression, and underlying respiratory illness are determinants of poor clinical outcomes, including greater mortality. Bacterial infections seem to be the main reason. Updated information on the role of bacterial infection as the cause of complications would be of value in improving the prognosis of patients with influenza. METHODS: A systematic review and meta-analysis were performed by using the PubMed repository using keywords like: Influenza, H1N1, Streptococcus pneumoniae, bacterial coinfection, secondary coinfection, bacterial complications in pneumonia, and seasonal influenza. Only articles written in English were included in publications from 2010 to 2020. The analyses were conducted following the preferred reporting items for systematic review and meta-analyses guidelines. The results were independently validated using a TrinetX database cohort of roughly 4 million patients. RESULTS: We included 135 studies that contained data from 48,259 patients hospitalized with influenza of any age. Bacterial infections were diagnosed in 5391 (11.2%). Streptococcus pneumoniae (30.7%) and Staphylococcus aureus (30.4%) were the most frequent microorganisms, followed by Haemophilus influenzae (7.1%) and Pseudomonas aeruginosa (5.9%). The random-effects model of the meta-analysis indicated that bacterial infections posed a 3.4-fold increased risk of death compared with influenza infection alone. Unexpectedly, asthma was protective (odds ratio 0.8). CONCLUSION: Bacterial infections diagnosed in 11.2% of patients with influenza increase 3.4-fold the mortality risk. S. pneumoniae, S. aureus, H. influenzae, and P. aeruginosa account for nearly 75% of the cases. Earlier diagnosis and use of antibiotics should improve outcomes in this population.

Artículo especial por el Día Mundial del Riñón: Las sociedades científicas españolas ante la guía ESC 2021 de prevención de la enfermedad vascular: generalizar la medida de la albuminuria para identificar el riesgo vascular y prevenir la enfermedad vascular / The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalising the measurement of albuminuria to identify vascular risk and prevent vascular disease

Las guías de 2021 sobre la prevención de la enfermedad vascular (EV) en la práctica clínica publicadas por la European Society of Cardiology (ESC) y apoyadas por otras 13 sociedades científicas europeas reconocen el papel clave de la detección de la enfermedad renal crónica (ERC) en la prevención de la EV. El riesgo vascular en la ERC se categoriza a partir de las medidas del filtrado glomerular estimado (FGe) y del cociente albúmina:creatinina en orina (ACRo). Así, la ERC moderada se asocia a un riesgo vascular alto y la ERC grave a un riesgo vascular muy alto, debiendo actuar en consecuencia desde el punto de vista terapéutico, sin que sea necesario aplicar otras puntuaciones de riesgo vascular cuando este ya es muy alto debido a la ERC. Es más, la ESC sitúa la medida del FGe y del ACRo en el inicio de la estimación del riesgo vascular y del algoritmo de decisión subsiguiente. A fin de optimizar la implementación de la guía 2021 de la ESC sobre la prevención de la EV en España, consideramos que: 1) El estudio de la orina para determinar la albuminuria mediante el ACRo debería formar parte de la rutina clínica al mismo nivel que el de la glucemia, la colesterolemia y la estimación del FG cuando estas se usan para tomar decisiones sobre el riesgo de EV. 2) Los servicios de salud públicos y privados españoles deberían disponer de los medios y recursos necesarios para implementar de forma óptima las Guías ESC 2021 de prevención de la EV en España, incluyendo la determinación del ACRo.(AU)

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies, recognise the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorised based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimise the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolaemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing. (AU)

Unravelling oligometastatic disease from the perspective of radiation and medical oncology. Part I: non-small cell lung cancer and breast cancer.

Oligometastatic disease (OMD) defines a cancer status that is intermediate between localized and widely spread metastatic disease, and can be treated with curative intent. While diagnostic imaging tools have considerably improved in recent years, unidentified micrometastases can still evade current detection techniques, allowing the disease to progress. The various OMD scenarios are mainly defined by the number of metastases, the biological and molecular tumour profiles, and the timing of the development of metastases. Increasing knowledge has contributed to the earlier and improved detection of OMD, underlining the importance of early disease control. In view of increasing OMD detection rates in current real-world clinical practice and the lack of standardized evidence-based guidelines to treat this cancer status, a board of experts from the Spanish Societies of Radiation Oncology (SEOR) and Medical Oncology (SEOM) organized a series of sessions to update the current state-of-the-art on OMD from a multidisciplinary perspective, and to discuss how results from clinical studies might translate into promising treatment options. This expert review series summarizes what is known and what it is pending clarification in the context of OMD in the scenarios of non-small cell lung cancer and breast cancer (Part I), and prostate cancer and colorectal cancer (Part II), aiming to offer specialists a pragmatic framework to help improve patient management.

A smartphone app to improve the safety of patients undergoing treatment with oral antineoplastic agents: 4 years of experience in a university hospital.

Objective: This study aims to analyze the impact of the eOncosalud app on the management and follow-up of adverse effects (AE) in patients receiving oral antineoplastic agents. Material and methods: We performed an observational, prospective study of cancer outpatients treated with oral antineoplastic agents (OAA), monitored by the eOncosalud app between August 2017 and October 2021. Safety variables were collected from eOncosalud: the number of AE; severity of the AE according to CTCAE, version 4.03; timelapse from app installation to first recorded AE; automatic recommendations issued; and the patient's acceptance of the recommendations made. To assess the impact of the recommendations generated by the algorithm, we calculated the positive predictive value (PPV) as the number of recommendations accepted out of the total number of recommendations generated. Safety-related patient messages were also analyzed (AE, drug-drug interactions, drug administration). Result: The app was downloaded and used by 186 patients (58.0% women), with a mean age of 59.0 years. A total of 1,368 AE were recorded, the most frequent being fatigue (19.37%), diarrhea (18.20%), and skin changes (9.21%). Regarding the recommendations issued by the app algorithm, 102 patients received 344 information brochures, 39 patients received 51 recommendations for supportive care to control AE, 60 patients received 240 recommendations to visit their primary care doctor, 14 patients received 16 recommendations to contact their specialist pharmacist or oncologist-hematologist, and 34 patients received 73 recommendations to go to the emergency room. The suggestion to go to the emergency room and contact the specialist pharmacist or oncologist-hematologist had a PPV of 0.51 and 0.35, respectively. Half of the patients (50.4%) used the messaging module. A total of 1,668 messages were sent. Of these, 47.8% were related to treatment safety: AE, 22.7%; drug-drug interactions, 20.6%; drug administration, 3.6%; and missing a dose, 1.0%. Conclusions: The eOncosalud app enables close, real-time monitoring of patients treated with OAA. The automatic recommendations through the app's algorithm have optimized available healthcare resources. The app facilitated early detection of AE, thus enabling patients themselves to improve the safety of their treatment.

SEOM-SOGUG clinical guideline for localized muscle invasive and advanced bladder cancer (2021)

Most muscle-invasive bladder cancer (BC) are urothelial carcinomas (UC) of transitional origin, although histological variants of UC have been recognized. Smoking is the most important risk factor in developed countries, and the basis for prevention. UC harbors high number of genomic aberrations that make possible targeted therapies. Based on molecular features, a consensus classification identified six different MIBC subtypes. Hematuria and irritative bladder symptoms, CT scan, cystoscopy and transurethral resection are the basis for diagnosis. Radical cystectomy with pelvic lymphadenectomy is the standard approach for muscle-invasive BC, although bladder preservation is an option for selected patients who wish to avoid or cannot tolerate surgery. Perioperative cisplatin-based neoadjuvant chemotherapy is recommended for cT2-4aN0M0 tumors, or as adjuvant in patients with pT3/4 and or pN + after radical cystectomy. Follow-up is particularly important after the availability of new salvage therapies. It should be individualized and adapted to the risk of recurrence. Cisplatin–gemcitabine is considered the standard first line for metastatic tumors. Carboplatin should replace cisplatin in cisplatin-ineligible patients. According to the EMA label, pembrolizumab or atezolizumab could be an option in cisplatin-ineligible patients with high PD-L1 expression. For patients whose disease respond or did not progress after first-line platinum chemotherapy, maintenance with avelumab prolongs survival with respect to the best supportive care. Pembrolizumab also increases survival versus vinflunine or taxanes in patients with progression after chemotherapy who have not received avelumab, as well as enfortumab vedotin in those progressing to first-line chemotherapy followed by an antiPDL1/PD1. Erdafitinib may be considered in this setting in patients with FGFR alterations. An early onset of supportive and palliative care is always strongly recommended.

SEOM-SOGUG clinical guideline for localized muscle invasive and advanced bladder cancer (2021).

Most muscle-invasive bladder cancer (BC) are urothelial carcinomas (UC) of transitional origin, although histological variants of UC have been recognized. Smoking is the most important risk factor in developed countries, and the basis for prevention. UC harbors high number of genomic aberrations that make possible targeted therapies. Based on molecular features, a consensus classification identified six different MIBC subtypes. Hematuria and irritative bladder symptoms, CT scan, cystoscopy and transurethral resection are the basis for diagnosis. Radical cystectomy with pelvic lymphadenectomy is the standard approach for muscle-invasive BC, although bladder preservation is an option for selected patients who wish to avoid or cannot tolerate surgery. Perioperative cisplatin-based neoadjuvant chemotherapy is recommended for cT2-4aN0M0 tumors, or as adjuvant in patients with pT3/4 and or pN + after radical cystectomy. Follow-up is particularly important after the availability of new salvage therapies. It should be individualized and adapted to the risk of recurrence. Cisplatin-gemcitabine is considered the standard first line for metastatic tumors. Carboplatin should replace cisplatin in cisplatin-ineligible patients. According to the EMA label, pembrolizumab or atezolizumab could be an option in cisplatin-ineligible patients with high PD-L1 expression. For patients whose disease respond or did not progress after first-line platinum chemotherapy, maintenance with avelumab prolongs survival with respect to the best supportive care. Pembrolizumab also increases survival versus vinflunine or taxanes in patients with progression after chemotherapy who have not received avelumab, as well as enfortumab vedotin in those progressing to first-line chemotherapy followed by an antiPDL1/PD1. Erdafitinib may be considered in this setting in patients with FGFR alterations. An early onset of supportive and palliative care is always strongly recommended.

Assessing Apps for Patients with Genitourinary Tumors Using the Mobile Application Rating Scale (MARS): Systematic Search in App Stores and Content Analysis.

BACKGROUND: The large number of available cancer apps and their impact on the population necessitates a transparent, objective, and comprehensive evaluation by app experts, health care professionals, and users. To date, there have been no analyses or classifications of apps for patients with genitourinary cancers, which are among the most prevalent types of cancer. OBJECTIVE: The objective of our study was to analyze the quality of apps for patients diagnosed with genitourinary cancers using the Mobile Application Rating Scale (MARS) and identify high-quality apps. METHODS: We performed an observational cross-sectional descriptive study of all smartphone apps for patients diagnosed with genitourinary cancers available on iOS and Android platforms. In July 2019, we searched for all available apps for patients with genitourinary cancers (bladder, prostate, cervical, uterine, endometrial, kidney, testicular, and vulvar) or their caregivers. Apps were downloaded and evaluated, and the general characteristics were entered into a database. The evaluation was performed by 2 independent researchers using the MARS questionnaire, which rates 23 evaluation criteria clustered in 5 domains (Engagement, Functionality, Esthetics, Information, and Subjective Quality) on a scale from 1 to 5. RESULTS: In total, 46 apps were analyzed. Of these, 31 (67%) were available on Android, 6 (13%) on iOS, and 9 (20%) on both platforms. The apps were free in 89% of cases (41/46), and 61% (28/46) had been updated in the previous year. The apps were intended for prostate cancer in 30% of cases (14/46) and cervical cancer in 17% (8/46). The apps were mainly informative (63%, 29/46), preventive (24%, 11/46), and diagnostic (13%, 6/46). Only 7/46 apps (15%) were developed by health care organizations. The mean MARS score for the overall quality of the 46 apps was 2.98 (SD 0.77), with a maximum of 4.63 and a minimum of 1.95. Functionality scores were quite similar for most of the apps, with the greatest differences in Engagement and Esthetics, which showed acceptable scores in one-third of the apps. The 5 apps with the highest MARS score were the following: "Bladder cancer manager," "Kidney cancer manager," "My prostate cancer manager," "Target Ovarian Cancer Symptoms Diary," and "My Cancer Coach." We observed statistically significant differences in the MARS score between the operating systems and the developer types (P<.001 and P=.01, respectively), but not for cost (P=.62). CONCLUSIONS: MARS is a helpful methodology to decide which apps can be prescribed to patients and to identify which features should be addressed to improve these tools. Most of the apps designed for patients with genitourinary cancers only try to provide data about the disease, without coherent interactivity. The participation of health professionals in the development of these apps is low; nevertheless, we observed that both the participation of health professionals and regular updates were correlated with quality.

Final Overall Survival Analysis of the SOGUG Phase 2 MAJA Study: Maintenance Vinflunine Versus Best Supportive Care After First-Line Chemotherapy in Advanced Urothelial Carcinoma.

INTRODUCTION: The MAJA study compared vinflunine (VFL) plus best supportive care (BSC) maintenance therapy versus BSC alone in advanced urothelial carcinoma responsive to first-line chemotherapy. The primary end point of progression-free survival was achieved. We present the final overall survival (OS) and long-term follow-up safety analyses. PATIENTS AND METHODS: Patients were enrolled, and a subsequent post hoc analysis was performed on the basis of radiologic response or stabilization to first-line cisplatin/gemcitabine (CG) chemotherapy (4-6 cycles), according to Response Evaluation Criteria in Solid Tumors (RECIST). VFL + BSC versus BSC alone were randomly assigned until disease progression. RESULTS: At final analysis, 58 patients (66.7%) had died while 29 (33.3%) had survived; the BSC arm had higher mortality (VFL + BSC, n = 26, 59.1% vs. BSC, n = 32, 74.4%). Median follow-up of surviving patients was 38.8 months (interquartile range, 23.8-61.6). Median OS was 16.7 months (95% confidence interval, 0-34.5) in VFL and 13.2 months (95% confidence interval, 6-20.4) in the BSC groups (hazard ratio, 0.736; 95% confidence interval, 0.44-1.24, P = .182). Post hoc group division did not affect median OS in either study arm. CONCLUSION: Final analysis supported a benefit of VFL in maintenance therapy in patients with disease control after first-line treatment with CG, with no unexpected long-term adverse effects. The study was insufficiently powered to show a significant OS advantage.

Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss.

PURPOSE: PI3K-Akt-mTOR and androgen receptor (AR) signaling are commonly aberrantly activated in metastatic castration-resistant prostate cancer (mCRPC), with PTEN loss associating with poor prognosis. We therefore conducted a phase Ib/II study of the combination of ipatasertib, an Akt inhibitor, with the CYP17 inhibitor abiraterone in patients with mCRPC.Patients and Methods: Patients were randomized 1:1:1 to ipatasertib 400 mg, ipatasertib 200 mg, or placebo, with abiraterone 1,000 mg orally. Coprimary efficacy endpoints were radiographic progression-free survival (rPFS) in the intent-to-treat population and in patients with PTEN-loss tumors. RESULTS: rPFS was prolonged in the ipatasertib cohort versus placebo, with similar trends in overall survival and time-to-PSA progression. A larger rPFS prolongation for the combination was demonstrated in PTEN-loss tumors versus those without. The combination was well tolerated, with no treatment-related deaths. CONCLUSIONS: In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors.See related commentary by Zhang et al., p. 901.

Weekly cabazitaxel plus prednisone is effective and less toxic for 'unfit' metastatic castration-resistant prostate cancer: Phase II Spanish Oncology Genitourinary Group (SOGUG) trial.

AIM: Cabazitaxel (CBZ), a novel tubulin-binding taxane, improves overall survival in metastatic castration-resistant prostate cancer (mCRPC) that progresses during or after docetaxel treatment. We have designed a phase II study to evaluate the efficacy and safety of CBZ as a weekly schedule for 'unfit' mCRPC patients after docetaxel failure. METHODS: In this single arm phase II study. CBZ was weekly administered in 1-hour infusion on days 1, 8, 15 and 22, every 5 weeks at 10 mg/m2 to eligible 'unfit' patients; oral prednisone (5 mg) was administered twice a day. Circulating tumour cells (CTCs) were also collected. New treatment scheme was considered effective if at least 65% of patients met a clinical benefit criteria based on prostate-specific antigen (PSA)-progression-free survival (PFS) values at week 12. RESULTS: Seventy patients (median age: 73.9 years) were enrolled; overall, 71.4% had an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 2; and 84%, 16% and 11% had bone, liver and lung metastases, respectively. Objective partial response or stable disease was achieved in 61% of patients, while PSA responses of ≥50% and ≥80% were observed in 34.8% and 10.6%, respectively. The median PSA-PFS was 4.8 months; and 68.6% of patients had no progression at week 12. The most frequent grade 3/4 toxicities were neutropenia (2.8%), leukopenia (5.7%) and thrombocytopaenia (9%); no cases of febrile neutropenia were reported. Early CTC response was significantly correlated with PSA-PFS. CONCLUSIONS: CBZ/prednisone administered weekly to 'unfit' mCRPC patients appears to be as effective as classical standard 3-week scheme (TROPIC study) but with significantly lower toxicities and better tolerance. Early CTC response appears to be valuable as an early end-point of therapeutic efficacy.

[Nutritional assessment and quality of life of oncology outpatients initiating treatment with tyrosine­kinase inhibitors]. / Seguimiento del estado nutricional y calidad de vida de pacientes que inician tratamiento con inhibidores tirosin kinasa.

BACKGROUND AND OBJECTIVE: The consumption of oral antineoplastics -and more particularly of tyrosine-kinase inhibitors (TKI)- has increased in recent years. These therapies show a better tolerance but still, the nutritional alterations related to their daily and chronic clinical use are under investigation. This study assesses the effects of TKI on the intake, nutritional status and micronutrients as well as the patients quality of life. METHODS: A prospective longitudinal study was conducted including adult patients having started some TKI treatment from July 2012 to June 2013, and a 6 month follow-up period was established. Demographic pharmacotherapeutic, nutritional and biochemical variables were collected and also a EORTC-QLQ30 questionnaire at baseline, first, third and sixth month of treatment. RESULTS: 31 patients were included in the study. The percentage of weight loss at treatment baseline was statistically matched to the results on the patient-generated Global Subjective Assessment. Appetite decreased after one month of treatment, and so did the calorie consumption; 62.1% of the patients lost weight, 55.5% on the third month and 70.6% on the sixth month. 6-17% of the patients suffered from malnutrition to some degree during the follow-up period and a decrease of calcium, phosphate and magnesium plasma levels was detected. The emotional scale was the one with a lowest score in EORTC QLQ-30, and fatigue and lack of appetite were the most common symptoms at treatment baseline, progressively increasing those of nausea, vomits and diarrhea. DISCUSSION: Patients treated with TKI did not show a relevant malnutrition. Considering the results, it is important to take into account weight loss at treatment baseline; it is also important to control calcium and phosphate levels during treatment, to advise and counsel the patient on the GI effects (nausea, vomits and diarrhea) and emotionally reinforce the patient.

Introducción y objetivo: El consumo de antineoplásicos orales y concretamente de inhibidores tirosin kinasa (ITK) se ha incrementado en los últimos años. Son terapias mejor toleradas y, sin embargo, las alteraciones nutricionales relativas a su uso clínico diario y crónico están aún en estudio. El presente estudio valora la repercusión de los ITK sobre la ingesta, estado nutricional y micronutrientes y valora la calidad de vida de estos pacientes. Métodos: Se realizó un estudio prospectivo y longitudinal en el que se incluyeron aquellos pacientes adultos que iniciaron tratamiento con algún ITK de julio 2012 a junio 2013 con un periodo de seguimiento de 6 meses. Se recogieron variables demográficas, farmacoterapéuticas, nutricionales, bioquímicas y el cuestionario EORTC-QLQ30 al inicio, primer, tercer y sexto mes de tratamiento. Resultados: Se incluyeron 31 pacientes. El porcentaje de pérdida de peso al inicio del tratamiento se relacionó estadísticamente con la clasificación de la Valoración Subjetiva Global-generada por el paciente. Tras un mes de tratamiento descendió el apetito, las calorías consumidas y un 62,1% de los pacientes perdió peso, 55,5% al tercer mes y 70,6% al sexto mes. Entre un 6-17% de los pacientes sufría algún grado de desnutrición durante el seguimiento y se detectó una disminución de los niveles plasmáticos de calcio, fosfato y magnesio. En el EORTC QLQ-30, la escala emocional fue la peor puntuada y los síntomas más comunes al inicio de tratamiento fueron la fatiga y pérdida de apetito, aumentando progresivamente las náuseas, vómitos y la diarrea. Discusión: Los pacientes tratados con ITK no presentaron una desnutrición importante. A la vista de los resultados es importante valorar la pérdida de peso al inicio de tratamiento, monitorizar los niveles de calcio y el fosfato durante el tratamiento, aconsejar y prevenir al paciente sobre los efectos gastrointestinales (náuseas, vómitos y diarrea) y reforzar emocionalmente al paciente.

SEOM clinical guidelines for treatment of prostate cancer.

Prostate cancer (PC) is the most common cancer in men. Many patients have prolonged survival and die of other diseases, so treatment decisions are often influenced by age and coexisting comorbidities. The main procedure to diagnose PC is an ultrasound-guided core needle biopsy, which is indicated when a digital rectal examination (DRE) finds nodularity or when PSA is >10 ng/ml, but is also recommended with PSA between 4.0 and 10 ng/ml. Depending on age, PSA, Gleason score and characteristics of the tumour, treatment options for localised PC are active surveillance, radical prostatectomy and radiation therapy. Androgen deprivation treatment (ADT) should be added to radiotherapy for men with intermediate- or high-risk PC. ADT is the current standard first-line treatment for metastatic PC. Castration-resistant PC is a heterogeneous entity. Several treatments such as sipuleucel-T, docetaxel-based chemotherapy, radium 223, cabazitaxel or abiraterone plus prednisone, zoledronic and denosumab, are useful for this situation.

Tratamiento del paciente con carcinoma de próstata en progresión bioquímica resistente a castración / Treatment of the patient with castration-resistant biochemical progression of prostate cancer

El carcinoma de próstata resistente a castración (CPRC) se define como la progresión tumoral a pesar de unos niveles eficaces de castración. (testosterona sérica < 50 ng/dL). La progresión bioquímica requiere al menos dos incrementos sucesivos en la cifra de antígeno prostático específico (PSA), separados al menos una semana, y con un valor mínimo de 2 ng/mL. In pacientes con bloqueo androgénico completo, se debe suspender al antiandrógeno antes del diagnóstico de CPRC. El CPRC es una entidad heterogénea. El valor basal de PSA y la velocidad de PSA parecen ser los factores pronósticos más importantes en pacientes con recidiva bioquímica como única manifestación del CPRC. Algunos de estos pacientes pueden ser seguidos sin tratamiento hasta la progresión de la enfermedad. Debido a que un gran porcentaje de tumores que progresan a pesar de la castración siguen siendo hormonodependientes, el empleo de otras terapias hormonales ha sido el tratamiento preferido para la mayoría de estos pacientes. Junto con los inhibidores de la esteroidogénesis suprarrenal, se están investigando actualmente otros enfoques más novedosos para inhibir el efecto del receptor androgénico activado sobre la célula tumoral. Recientemente, ha habido un importante desarrollo de la inmunoterapia, que ha demostrado incrementar la supervivencia en pacientes con CPRC oligosintomáticos. La quimioterapia de primera y segunda línea en CPRC se asocia con incremento de supervivencia, pero generalmente se recomienda para pacientes con metástasis. Hasta que estén disponibles los resultados de ensayos clínicos actualmente en marcha, el tipo y secuencia de tratamientos para los pacientes con CPRC y recaída bioquímica debe realizarse de forma individualizada(AU)

Castration resistant prostatic carcinoma (CRPC) is defined as tumor progression despite an effective castration (serum testosterone levels < 50 ng/dL). Biochemical progression requires at least two successive increases from the previous lowest value of serum prostate-specific antigen (PSA) spaced at least a week, and with a minimum value of 2 ng/mL. In patients receiving complete androgen blockade, antiandrogen should be discontinued prior to diagnosis of CRPC. CPRC is a heterogeneous entity. Baseline PSA and PSA velocity seem to be the most important prognostic factors in patients with biochemical relapse as the only manifestation of CRPC. Some of these patients can be followed without treatment until disease progression. Because of a large proportion of tumors progressing under androgen deprivation therapy remain hormone-dependent, the use of other hormonal therapies has been the preferred treatment for the majority of these patients. Besides inhibitors of adrenal steroidogenesis, other novel hormonal approaches are currently under investigation to avoid the effect of the activated androgenic receptor on the tumor cell. In recent years there has been an important development of immunotherapy, which has demonstrated to increase survival in CRPC oligosymptomatic patients. First and second line chemotherapy in CRPC are associated with an increase in overall survival, but they are usually recommended for patients with metastases. Until the results of ongoing trials are available, the type and timing of the treatment for patients with CRPC and biochemical recurrence should be individualized(AU)

[Effectivity of thalidomide and dexamethasone for the treatment of refractory multiple myeloma: a retrospective study of 36 consecutive cases]. / Efectividad de la talidomida y la dexametasona en el tratamiento del mieloma múltiple resistente al tratamiento: estudio retrospectivo de 36 casos consecutivos.

BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) is a plasm-cell neoplasm characterized by a monoclonal protein in the serum or urine. Thalidomide is effective as second line treatment. PATIENTS AND METHOD: We performed a retrospective study of 36 consecutive patients with refractory MM treated with thalidomide and dexamethasone as second line therapy, with the objective of analyzing the rate of response (primary end point), progression-free survival (PFS) and toxicity profiles (second end points). RESULTS: In our study the overall response rate was 55.6%, with a median of PFS of 12.6 months (95% confidence interval: 4-21 months). PFS at 6, 12 and 18 months was 61.11%, 50% and 22.22% respectively. 30.6% of the patients had neuropathy, 11.11% had rash and 5.55% had deep vein thrombosis. CONCLUSIONS: The combination of thalidomide and dexamethasone is an effective and safe second line treatment for refractory MM, with a manageable toxicity.

Efectividad de la talidomida y la dexametasona en el tratamiento del mieloma múltiple resistente al tratamiento: estudio retrospectivo de 36 casos consecutivos / Effectivity of thalidomide and dexamethasone for the treatment of refractory multiple myeloma: a retrospective study of 36 consecutive cases

Fundamento y objetivo: El mieloma múltiple (MM) es una neoplasia de células plasmáticas que se caracteriza por la presencia de una proteína monoclonal en suero u orina. La talidomida es un fármaco eficaz en el tratamiento de segunda línea de esta enfermedad. Pacientes y método: Hemos realizado un estudio retrospectivo de una serie de 36 casos consecutivos con MM pertinaz a los que hemos tratado con talidomida y dexametasona en segunda línea, con el objetivo de analizar la tasa de respuesta (objetivo primario), la supervivencia libre de progresión (SLP) y toxicidad (objetivos secundarios). Resultados: En nuestro estudio hemos encontrado una tasa de respuesta total del 55,6%, una mediana de SLP de 12,6 meses (intervalo de confianza del 95%, 4-21 meses). La SLP a los 6, 12 y 18 meses fue del 61,11, el 50 y el 22,22% respectivamente. El 30,6% de los pacientes presentaron neuropatía; el 11,11%, erupción cutánea y el 5,55%, enfermedad tromboembólica. Conclusiones: La combinación de talidomida y dexametasona es un tratamiento efectivo y seguro en segunda línea para pacientes con MM resistente al tratamiento, con una toxicidad manejable

Background and objective: Multiple myeloma (MM) is a plasm-cell neoplasm characterized by a monoclonal protein in the serum or urine. Thalidomide is effective as second line treatment. Patients and method: We performed a retrospective study of 36 consecutive patients with refractory MM treated with thalidomide and dexamethasone as second line therapy, with the objective of analyzing the rate of response (primary end point), progression-free survival (PFS) and toxicity profiles (second end points). Results: In our study the overall response rate was 55.6%, with a median of PFS of 12.6 months (95% confidence interval: 4-21 months). PFS at 6, 12 and 18 months was 61.11%, 50% and 22.22% respectively. 30.6% of the patients had neuropathy, 11.11% had rash and 5.55% had deep vein thrombosis. Conclusions: The combination of thalidomide and dexamethasone is an effective and safe second line treatment for refractory MM, with a manageable toxicity