Docetaxel combined with irinotecan or 5-fluorouracil in patients with advanced oesophago-gastric cancer: a randomised phase II study.

BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.

Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients. METHODS: Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis. RESULTS: Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP â†’ ENZ and ENZ â†’ AAP; it was found that sequence of AAP â†’ ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ â†’ AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc â†’ AAP â†’ ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP â†’ ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc â†’ ENZ â†’ AAP sequence, PSA response rates were much lower than those reported with Doc â†’ AAP â†’ ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%. CONCLUSION: Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ â†’ AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.

Latest progress in molecular biology and treatment in genitourinary tumours.

The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study.

BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).

SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017).

Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.

Correction to: SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017).

The original article shows two mistakes, which are listed here.

Consensus statement on definition, diagnosis, and management of high-risk prostate cancer patients on behalf of the Spanish Groups of Uro-Oncology Societies URONCOR, GUO, and SOGUG.

PURPOSE: Prostate cancer (PCa) is the most prevalent malignancy in men and the second cause of mortality in industrialized countries. METHODS: Based on Spanish Register of PCa, the incidence of high-risk PCa is 29%, approximately. In spite of the evidence-based beneficial effect of radiotherapy and androgen deprivation therapy in high-risk PCa, these patients (pts) are still a therapeutic challenge for all specialists involved, in part due to the absence of comparative studies to establish which of the present disposable treatments offer better results. RESULTS: Nowadays, high-risk PCa definition is not well consensual through the published oncology guides. Clinical stage, tumour grade, and number of risk factors are relevant to be considered on PCa prognosis. However, these factors are susceptible to change depending on when surgical or radiation therapy is considered to be the treatment of choice. Other factors, such as reference pathologist, different diagnosis biopsy schedules, surgical or radiotherapy techniques, adjuvant treatments, biochemical failures, and follow-up, make it difficult to compare the results between different therapeutic options. CONCLUSIONS: This article reviews important issues concerning high-risk PCa. URONCOR, GUO, and SOGUG on behalf of the Spanish Groups of Uro-Oncology Societies have reached a consensus addressing a practical recommendation on definition, diagnosis, and management of high-risk PCa.

Update in the management of ovarian and cervical carcinoma.

Ovarian and cervical cancers are significant health problems. This article provides an update in selected management topics. Paclitaxel and platinum derivatives are the first-line treatment for patients with advanced disease. In selected patients, intraperitoneal chemotherapy has been associated with improved survival but the broad applicability of this strategy is limited by issues of toxicity and feasibility. Management of patients with recurrent disease is based on a number of factors and includes surgery in selected cases, platinum-based chemotherapy for patients with platinum-sensitive disease and other agents such as topotecan and pegylated liposomal formulation of doxorubicin for patients with platinum-resistant disease. In cervical cancer, the most significant issue/event is the demonstration of superior survival with topotecan and cisplatin compared to cisplatin alone. Finally, new agents such as epidermal growth factor receptor inhibitors and antiangiogenic agents are being currently tested in these settings.

Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy.

The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy.

Role of taxanes in advanced prostate cancer.

Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration-resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer.

SEOM Clinical Guideline for bone metastases from solid tumours (2016).

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosumab, an anti-RANKL monoclonal antibody. Both reduce the risk and/or delay the development of SREs in several types of tumours. Radium 233, an alpha-particle emitter, increases overall survival in patients with bone metastases from resistant castration prostate cancer. Multidisciplinary approach is essential and bone surgery and radiotherapy should be integrated in the treatment of bone metastases when necessary. This SEOM Guideline reviews bone metastases pathogenesis, clinical presentations, lab tests, imaging techniques for diagnosis and response assessment, bone-targeted agents, and local therapies, as radiation and surgery, and establishes recommendations for the management of patients with metastases to bone.

Management of infection and febrile neutropenia in patients with solid cancer.

An expert group from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, for its acronym in Spanish) and the Spanish Society of Medical Oncology (SEOM, for its acronym in Spanish) have reviewed the main aspects to be considered when evaluating patients with solid cancer and infectious complications contained in this article. Recommendations have, therefore, been put forth regarding the prophylaxis of the most prevalent infections in these patients, the use of vaccines, measures to control infection through vascular catheters, and preventing infection in light of certain surgical maneuvers. The following is a revision of the criteria for febrile neutropenia management and the use of colony-stimulating factors and closes with several guidelines for treating the cancer patient with serious infection. The document concludes with a series of measures to control hospital infection.

A comparative study of ejaculate traits in three endangered ungulates with different levels of inbreeding: fluctuating asymmetry as an indicator of reproductive and genetic stress.

We studied three closely related species of endangered gazelles (Gazella dorcas, Gazella dama and Gazella cuvieri) with different levels of inbreeding in order to determine at which intensities inbreeding influences ejaculate traits. We also examined whether fluctuating asymmetry (FA) is a reliable indicator of genetic as well as reproductive stress. Our results show that, within each population, the individual coefficient of inbreeding is inversely related to ejaculate quality only in the species with the highest levels of inbreeding (G. cuvieri). In addition, FA is a reliable indicator of individual levels of inbreeding in both the species with the highest levels of inbreeding (G. cuvieri) and the species with intermediate levels of inbreeding (G. dama). Thus, FA appears in individuals whose levels of inbreeding are still not high enough to affect male reproductive potential and should therefore be considered a sensitive indicator of genetic stress. Finally, FA is also a reliable indicator of male reproductive stress since it is related to individual semen quality in all the species studied.

Inbreeding, fluctuating asymmetry, and ejaculate quality in an endangered ungulate.

An ever-increasing number of species are suffering marked reductions in population size as a consequence of human activities. To understand the impact of these changes it is essential to assess how small population size affects individual fitness and the viability of populations. This issue acquires special relevance among endangered species in which numbers have decreased to such an extent that captive breeding must be established with a few founders. A major risk associated with small population size is inbreeding depression. The effects of inbreeding upon male reproductive traits are the subject of an ongoing controversy, since the evidence linking lack of genetic variability and poor ejaculate quality at the population level has been criticized recently by several authors. We report that among Gazella cuvieri males, inbreeding coefficient shows a strong inverse relationship with ejaculate quality. Furthermore, the degree of fluctuating asymmetry is positively related to the coefficient of inbreeding and negatively related to the proportion of normal sperm, suggesting that it is a reliable indicator of genetic stress and of ejaculate quality.

Phase II study of weekly irinotecan (CPT-11) as second-line treatment of patients with advanced colorectal cancer.

This phase II trial studied the antitumor effect and toxicity of weekly irinotecan (CPT-11, 125 mg/m(2) 60 min iv infusion, weekly for 4 wk plus 2 wk rest) as second-line chemotherapy in patients with advanced colorectal cancer (CRC) resistant or refractory to prior 5-fluorouracil (5-FU) therapy. Sixty-nine patients with adenocarcinoma (57% in the colon and 43% in the rectum) were enrolled. The median number of treatment cycles received per patient was 4 (range, 1-6). Overall response rate was 18% (95% CI, 9-26), with 4 complete responses (6%) and 8 partial responses (12%), and a median duration of response of 8.1 mo (95% CI, 4.2-12.1). Stable disease was observed in 19 patients (28%). The median time to disease progression was 5.2 mo (95% CI, 4.3-6.1), and the median overall survival was 13.3 mo (95% CI, 9.8-16.8 months). The toxicity profile was favorable: grade 3/4 delayed diarrhea was observed in 10 patients (14.5%) in one cycle each, and grade 3/4 neutropenia in 6 patients (8.7%) and 6 cycles (3.3%). No febrile neutropenia or infection was documented. Grade 3/4 nausea and vomiting were reported in 1 (1.4%) and 7 patients (10.1%), respectively. In conclusion, this phase II trial showed a response rate and a toxicity profile of weekly CPT-11 in line with the results of prior phase II studies.

SEOM clinical guidelines for the treatment of metastatic prostate cancer.

Androgen deprivation treatment is the current standard first-line treatment for metastatic prostate cancer. For several years, docetaxel was the only treatment with a proven survival benefit for castration-resistant prostate cancer (CRPC). Since docetaxel became standard of care for men with symptomatic metastatic castration-resistant prostate cancer (CRPC), three treatment virtual spaces, for treatment and drug development in CPRC, have emerged: pre-docetaxel, docetaxel combinations and post-docetaxel. Sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 have been approved in the pre- or post-docetaxel setting in metastatic CRPC during the last few years. Patients are now living longer and experiencing better quality of life. Strategies for patient selection and treatment sequencing are therefore urgently required.

Characterization of the estrous cycle and reproductive traits of the aoudad (Ammotragus lervia) in captivity.

In this study the estrous cycle of the aoudad has been analyzed and characterized for the first time, using non-invasive methods for tracking reproductive cyclicity. The duration of the estrous cycle is 23 days (range 16-32 days), with a luteal phase of 17 days (range 12-27 days) and an interluteal phase of 6 days (range 3-14 days). The estrous cycle did not differ between females, but it was affected by the time of the year. Intraindividual variation of the cycle was observed in one out of the nine individuals. The average hormone concentration values, the estrogen:progestogen ratio, as well as their minimum and maximum values for each interluteal and luteal phases of the estrous cycle, are shown. Interindividual differences found in these values were basically associated with age. Females tended to start their cycle when in the presence of an adult male. Anestrus was observed in study females except for the oldest (14 years old). Age and anestrus onset were correlated, with younger females starting earlier than the older ones. This study reveals that Ammotragus reproductive biology is more similar to that of Capra than Ovis, except for some endocrinological features.

Pain in clinical oncology: patient satisfaction with management of cancer pain.

BACKGROUND: Despite effective analgesic therapy, inadequate pain control is frequently perceived by patients and caregivers. AIMS: To assess satisfaction with management of pain in cancer patients. METHODS: Between January and May 2007, a cross-sectional multicentre study was conducted in 64 Medical Oncology Departments throughout Spain. A total of 525 outpatients with oncological diseases completed a questionnaire with demographic data, characteristics and intensity of pain, and perceptions and attitudes towards pain management at the time of a routine clinical visit. Physicians also completed a questionnaire with tumour-related and treatment-related data. Cluster analysis was used to classify patients into three groups (satisfied, neither satisfied nor dissatisfied or neutral, dissatisfied) according to pain intensity and satisfaction with treatment. RESULTS: Patients satisfied with their analgesic treatment (33%) had lower pain intensities and, when regularly asked about their pain, considered their physicians to be more involved in their treatment. Neither satisfied nor dissatisfied patients (neutral) (44%) had higher mean pain intensities. Two-thirds of them achieved marked relief of their pain and also thought that physicians were aware of their situation. Dissatisfied patients (23%) had moderate to severe pain intensities, and said that they were asked less frequently about their pain, and thought that their physicians were less involved in their analgesic treatment. CONCLUSION: Physician-patient communication and information provided to patients are essential aspects of patient perceptions and attitudes towards control of cancer-related pain. Pain is seen as a condition that may be controlled but affects the capacity to lead a normal life.

Seasonality and edge effect determine herbivory risk according to different plant association models.

We report evidence of hierarchical resource selection by large herbivores and plant neighbouring effects in a Mediterranean ecosystem. Plant palatability was assessed according to herbivore foraging decisions. We hypothesize that under natural conditions large herbivores follow a hierarchical foraging pattern, starting at the landscape scale, and then selecting patches and individual plants. A between- and within-patch selection study was carried out in an area formed by scrubland and pasture patches, connected by habitat edges. With regard to between-patch selection, quality-dependent resource selection is reported: herbivores mainly consume pasture in spring and woody plants in winter. Within-patch selection was also observed in scrub habitats, influenced by season, relative patch palatability and edge effect. We defined a Proximity Index (PI) between palatable and unpalatable plants, which allowed verification of neighbouring effects. In spring, when the preferred food resource (i.e. herbs) is abundant, we observed that in habitat edges large herbivores basically select the relatively scarce palatable shrubs, whereas inside scrubland, unpalatable shrub consumption was related to increasing PI. In winter, a very different picture was observed; there was low consumption of palatable species surrounded by unpalatable species in habitat edges, where the latter were more abundant. These outcomes could be explained though different plant associations described in the literature. We conclude that optimal foraging theory provides a conceptual framework behind the observed interactions between plants and large herbivores in Mediterranean ecosystems.

A prospective observational study of the effectiveness, safety, and effect on fatigue of darbepoetin alfa for the treatment of chemotherapy-induced anaemia.

OBJECTIVE: Anaemia is common in cancer patients treated with chemotherapy. Darbepoetin alfa (DA) is the only erythropoiesis-stimulating protein approved for administration at weekly and every-three-week intervals in cancer patients receiving chemotherapy. This article investigates the effectiveness, tolerability and effect on fatigue of DA. METHODS: Prospective, observational study performed in 30 Spanish centres. Eligible patients were > or = 18 years of age, anaemic (haemoglobin [Hb] < or = 11 g/dL), with non-myeloid malignancies, receiving chemotherapy. DA (150 mug) was administered weekly for a maximum of 16 weeks (dosage doubled if Hb increased < 1 g/dL after 4 weeks). MAIN OUTCOME MEASURES: Haematopoietic response (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of transfusions in the previous 28 days), transfusion required between Weeks 5 and 16 and fatigue measured by the Fatigue subscale of the Functional Assessment of Cancer Therapy. RESULTS: 293 adults were recruited (56.4% women), with lymphoproliferative malignancies (44.3%) or solid tumours (55.7%). Baseline Hb was 9-11 g/dL in 83.7% of patients. Sixty-four per cent (95% CI: 58.1-69.4%) had a haematopoietic response and 12% required transfusions. After adjusting for performance status, concomitant diseases and chemotherapy type, an increase in Hb level was significantly associated with an improvement in Fatigue subscale (+1.9 points per 1 g/dL). Only 2% of patients had treatment-related adverse events: thromboembolic pulmonary disease (0.3%); hypersensitivity reaction (0.3%); local pain following DA administration (0.3%); insomnia (0.3%); thrombocytosis (0.3%) and deep vein thrombosis (0.3%). CONCLUSIONS: Fixed-dose DA administered once weekly seems to be an effective, well-tolerated treatment for chemotherapy-induced anaemia in patients with non-myeloid malignancies, and there is an indication of a possible benefit on fatigue in the clinical practice.