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1.
Gastric Cancer ; 27(1): 131-145, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37964032

ABSTRACT

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Female , Young Adult , Humans , Aged , Stomach Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Progression-Free Survival , Adenocarcinoma/pathology , Registries
3.
BMJ Open ; 13(11): e076849, 2023 11 09.
Article in English | MEDLINE | ID: mdl-37945304

ABSTRACT

OBJECTIVE: The objective of this study is to characterise the self-reported first contact with the health system and the reasons stated for each choice, testing associations with population characteristics. DESIGN: Cross-sectional survey. SETTING: Primary care department of a local health unit in northern Portugal. PARTICIPANTS: Random sample of 4286 persons, retrieved from all registered adults. OUTCOMES: Participants who stated they usually see the same doctor when a health problem arises were considered to adopt first-contact care and were asked to identify their regular doctor. Participants were asked why they adopt first-contact care or why they choose to do otherwise. Associations between personal characteristics and the adoption of first-contact care were tested using logistic regression. RESULTS: There were 808 valid questionnaires received (19% response rate). The mean age of respondents was 53 years, 58% were women and 60% had a high school or higher degree. Most (71%) stated always seeing the same doctor when facing a health problem. This was a general practitioner (GP) in 84%. The main reasons were previous knowledge and trust in the doctor. When this doctor was not a GP, the main reason was the need to obtain an appointment quickly. Participants who chose first-contact care were less likely to have university degrees than those who did not (OR 0.31; 95% CI 0.13 to 0.76). Being registered with the same GP for over 1 year increased the odds of adopting first-contact care: twice as likely for those registered for 1-4 years with the same GP (2.07; 95% CI 1.04 to 4.11), and three times more likely for those registered for over 10 years (3.21; 95% CI 1.70 to 6.08). CONCLUSIONS: The high adoption of first-contact care and the reasons given for this suggest a strong belief in primary care in this population. The longer patients experience continuity, the more they adopt first-contact care. The preferences of higher-educated patients regarding first-contact care deserve reflection.


Subject(s)
General Practitioners , Adult , Humans , Female , Middle Aged , Male , Cross-Sectional Studies , Portugal , Surveys and Questionnaires , Self Report
4.
PLoS One ; 18(5): e0285899, 2023.
Article in English | MEDLINE | ID: mdl-37220164

ABSTRACT

BACKGROUND: In 2020, Portugal had high levels of unmet health care needs. Primary Care was reported as the main source of unmet needs. OBJECTIVES: To describe face-to-face and remote access to GPs in Portugal during the COVID-19 pandemic. To discover patient experiences and attitudes to access to care. To identify determinants of access to care. METHODS: A survey of a random sample of 4,286 adults registered in a group of Family Practices was conducted in 2021. Paper questionnaires were sent by post to patients who had no e-mail address registered with the practice. Patients with an e-mail address were sent a link to an online questionnaire. Outcomes were reported waiting times for face-to-face and remote contacts with GPs, dichotomized to ascertain compliance with standards. Associations between participant characteristics and outcome variables were tested using logistic regression. RESULTS: Waiting times for face-to-face consultations with GPs during the pandemic often exceeded the maximum waiting times (MWT) set by the National Health Service. Remote contacts were mostly conducted within acceptable standards. Waiting times for speaking with the GP over the phone were rated as 'poor' by 40% and 27% reported requests for these calls as unmet. The odds of getting care over MWT increased for participants who reported poorer digital skills. Participants were less likely to get non-urgent consultations over MWT if they found it easy to use the online patient portal to book appointments (odds ratio 0.24; 99% confidence intervals 0.09-0.61), request prescriptions (0.18; 0.04-0.74) or insert personal data (0.18; 0.04-0.95). CONCLUSION: Patient reported access to GPs during the pandemic was uneven in Portugal. Obtaining non-urgent consultations and remote contacts over MWT affected mainly those patients with poor digital skills. Telephone access to GPs received the worse ratings. Access through traditional pathways must remain available, to prevent the widening of inequities.


Subject(s)
COVID-19 , General Practitioners , Adult , Humans , Portugal , Pandemics , State Medicine , Patient Outcome Assessment
5.
Ther Adv Med Oncol ; 15: 17588359231157641, 2023.
Article in English | MEDLINE | ID: mdl-36895850

ABSTRACT

Background: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13-8.25] and 14.0 months (95% CI, 13.0-14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578-0.636) and 0.623 (95% CI, 0.594-0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints.

6.
BMC Prim Care ; 24(1): 46, 2023 02 13.
Article in English | MEDLINE | ID: mdl-36782109

ABSTRACT

BACKGROUND: The Portuguese National Health System (NHS) provides universal coverage and near-free health care, but the population has high out-of-pocket expenses and unmet care needs. This suggests impaired accessibility, a key dimension of primary care. The COVID-19 pandemic has further affected access to health care. Understanding General Practitioners' (GP) experiences during the pandemic is necessary to reconfigure post-pandemic service delivery and to plan for future emergencies. This study aimed to assess accessibility to GPs, from their perspective, evaluating determinants of accessibility during the second pandemic year in Portugal. METHODS: All GPs working in NHS Family Practices in continental Portugal were invited to participate in a survey in 2021. A structured online self-administered anonymous questionnaire was used. Accessibility was assessed through waiting times for consultations and remote contacts and provision of remote access. NHS standards were used to assess waiting times. Descriptive statistics were used to characterize the study sample. Associations between categorical variables were tested using the χ2 statistic and the Student t-test was used to compare means of continuous variables. RESULTS: A total of 420 GPs were included (7% of the target population). Median weekly working hours was 49.0 h (interquartile range 42.0-56.8), although only 14% reported a contracted weekly schedule over 40 h. Access to in-person consultations and remote contacts was reported by most GPs to occur within NHS time standards. Younger GPs more often reported waiting times over these standards. Most GPs considered that they do not have enough time for non-urgent consultations or for remote contacts with patients. CONCLUSIONS: Most GPs reported compliance with standards for waiting times for most in-person consultations and remote contacts, but they do so at the expense of work overload. A persistent excess of regular and unpaid working hours by GPs needs confirmation. If unpaid overtime is necessary to meet the regular demands of work, then workload and specific allocated tasks warrant review. Future research should focus on younger GPs, as they seem vulnerable to restricted accessibility. GPs' preferences for more in-person care than was feasible during the pandemic must be considered when planning for the post-pandemic reconfiguration of service delivery.


Subject(s)
COVID-19 , General Practitioners , Humans , COVID-19/epidemiology , Pandemics , Portugal/epidemiology , Surveys and Questionnaires , Health Services Accessibility
7.
J Cancer Res Clin Oncol ; 149(7): 4077-4089, 2023 Jul.
Article in English | MEDLINE | ID: mdl-36042046

ABSTRACT

PURPOSE: This study aimed to compare ramucirumab-paclitaxel versus chemotherapy in second-line (2L) advanced gastroesophageal cancer (aGEC) based on HER2 status and analyze prognostic factors. METHODS: The study includes patients from the AGAMENON-SEOM registry with aGEC and known HER2 status who received 2L between 2016 and 2021. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) and multivariable Cox regression analysis was done to adjust for confounding variables. RESULTS: Of the 552 patients who met the selection criteria, 149 (26.9%) had HER2-positive aGEC, 89 were treated with chemotherapy, and 60 with ramucirumab-paclitaxel, and 403 had an HER2-negative aGEC, 259 were treated with chemotherapy, and 144 with ramucirumab-paclitaxel. In the whole sample, 2L PFS was 3.0 months (95% CI 2.8-3.2), 2L OS, 5.7 months (5.2-6.3), and ramucirumab-paclitaxel versus chemotherapy was associated with increased PFS (HR 0.64, 95% CI 0.53-0.78, p < 0.0001) and OS (HR 0.68, 0.55-0.83, p = 0.0002). Median PFS of ramucirumab- paclitaxel versus chemotherapy was 3.5 vs 2.8 months (HR 0.67, 0.54-0.83, p = 0.0004) in HER2-negative, and 4.7 vs 2.7 months (HR 0.57, 0.40-0.82, p = 0.0031) in HER2-positive aGEC, respectively. Median OS for ramucirumab-paclitaxel versus chemotherapy was 6.6 vs 5 months (HR 0.67, 0.53-0.85, p = 0.0007) in HER2-negative, and 7.4 vs 5.6 months (HR 0.70, 0.53-1.04, p = 0.083) in HER2-positive aGEC, respectively. ECOG-PS, tumor burden, Lauren subtype, and neutrophil-lymphocyte ratio were prognostic factors. CONCLUSIONS: In patients with an aGEC from the AGAMENON-SEOM registry, 2L treatment with ramucirumab-paclitaxel was superior to chemotherapy in PFS, OS and response rate, independent of HER2 status.


Subject(s)
Adenocarcinoma , Stomach Neoplasms , Humans , Paclitaxel , Antibodies, Monoclonal/therapeutic use , Stomach Neoplasms/pathology , Adenocarcinoma/pathology , Registries , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ramucirumab
8.
Ther Adv Med Oncol ; 13: 17588359211019672, 2021.
Article in English | MEDLINE | ID: mdl-34211587

ABSTRACT

BACKGROUND: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. METHODS: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. RESULTS: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). CONCLUSION: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.

9.
Gastric Cancer ; 24(4): 926-936, 2021 07.
Article in English | MEDLINE | ID: mdl-33651195

ABSTRACT

BACKGROUND: Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical trials rarely include EAC. This work sought to compare clinical characteristics and treatment outcomes of advanced EAC with those of GEJ-AC and GAC and examine prognostic factors. PATIENTS AND METHODS: Participants comprised patients with advanced EAC, intestinal GEJ-AC, and GAC treated with platin and fluoropyrimidine (plus trastuzumab when HER2 status was positive). Overall and progression-free survival were estimated using the Kaplan-Meier method. Cox proportional hazards regression gauged the prognostic value of the AGAMENON model. RESULTS: Between 2008 and 2019, 971 participants from the AGAMENON-SEOM registry were recruited at 35 centers. The sample included 67.3% GAC, 13.3% GEJ-AC, and 19.4% EAC. Pulmonary metastases were most common in EAC and peritoneal metastases in GAC. Median PFS and OS were 7.7 (95% CI 7.3-8.0) and 13.9 months (12.9-14.7). There was no difference in PFS or OS between HER2- and HER2+ tumors from the three locations (p > 0.05). Five covariates were found to be prognostic for the entire sample: ECOG-PS, histological grade, number of metastatic sites, NLR, and HER2+ tumors treated with trastuzumab. In EAC, the same variables were prognostic except for grade. The favorable prognosis for HER2+ cancers treated with trastuzumab was homogenous for all three subgroups (p = 0.351) and, after adjusting for the remaining covariates, no evidence supported primary tumor localization as a prognostic factor (p = 0.331). CONCLUSION: Our study supports the hypothesis that EAC exhibits clinicopathological characteristics, prognostic factors, and treatment outcomes comparable to intestinal GEJ-AC and GAC.


Subject(s)
Adenocarcinoma/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/mortality , Stomach Neoplasms/mortality , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/pathology , Esophagogastric Junction/pathology , Female , Humans , Intestines/pathology , Kaplan-Meier Estimate , Male , Middle Aged , Prognosis , Progression-Free Survival , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Registries , Retrospective Studies , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Trastuzumab/therapeutic use , Treatment Outcome
10.
Int J Cancer ; 148(10): 2389-2397, 2021 May 15.
Article in English | MEDLINE | ID: mdl-33270902

ABSTRACT

Coronavirus disease 2019 (COVID-19) pandemic is affecting a high percentage of the population at an unprecedented rate. Cancer patients comprise a subgroup especially vulnerable to this infection. Herein, we present a prospective analysis of epidemiological, clinical, radiological and laboratory data of consecutive adult cancer patients seen in the Clínico San Carlos University Hospital (Madrid, Spain), and admitted to hospital and tested for COVID-19 between 21 February 2020 and 8 May 2020 due to clinical suspicion of infection. Data from 73 patients with confirmed COVID-19 and active solid tumors or diagnosed within the previous 5 years were analyzed. The most frequent malignancy was lung cancer (19%) and 54 patients (74%) were on active cancer treatment. Most common findings on presentation included cough (55%), fever (52%) and dyspnea (45%), and 32 (44%) patients showed oxygen saturation levels below 95%. Radiologically, 54 (73%) patients presented an abnormal pattern, the most frequent being infiltrates (64%). 18 (24.7%) patients died in hospital and 55 (75.3%) were discharged with clinical resolution of the event. Multivariable logistic regression adjusted for age and tumor stage showed higher odds of in-hospital death associated with a history of cardiovascular disease, hospitalization in the previous 30 days, and several features on admission including dyspnea, higher qSOFA score, higher C-reactive protein levels and an abnormal neutrophil count. We present prospective, real-world evidence that can help articulate cancer care protocols for patients infected with SARS-CoV-2, with special focus on features on admission that can stratify patients with a higher risk of death from COVID-19.

11.
Gastric Cancer ; 24(2): 445-456, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32970266

ABSTRACT

BACKGROUND: The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. METHODS: The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. RESULT: The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15-1.40), and TR 1.19 (95% CrI, 1.09-1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08-1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09-1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. CONCLUSION: Our study confirms the effect of DPF is highly dependent on several clinical-pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Clinical Trials as Topic/statistics & numerical data , Docetaxel/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Bayes Theorem , Female , Humans , Male , Middle Aged , Platinum Compounds/therapeutic use , Product Surveillance, Postmarketing , Progression-Free Survival , Prospective Studies , Pyrimidines/therapeutic use , Registries , Stomach Neoplasms/mortality , Survival Rate , Treatment Outcome , Young Adult
12.
PLoS One ; 15(7): e0235848, 2020.
Article in English | MEDLINE | ID: mdl-32735623

ABSTRACT

BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Registries/statistics & numerical data , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Drug Utilization/statistics & numerical data , Female , Humans , Male , Middle Aged , Platinum Compounds/administration & dosage , Platinum Compounds/therapeutic use , Stomach Neoplasms/pathology , Survival Analysis
13.
Expert Opin Biol Ther ; 20(1): 15-22, 2020 01.
Article in English | MEDLINE | ID: mdl-31608707

ABSTRACT

Introduction: In colorectal cancer, anti-VEGF agents have demonstrated a survival benefit when combined with chemotherapy. However, development of resistance is very common. One of the mechanisms is due not to a failure in the VEGFR blockade, but rather to development of compensatory mechanisms of resistance, such as hypoxia-triggered upregulation of other proangiogenic factors, like placental growth factor (PlGF).Areas covered: This article summarizes the fundamental role of PlGF in the development of resistance to antiangiogenic treatment as well as the efficacy of aflibercept, ramucirumab, and regorafenib.Expert opinion: Aflibercept functions as a soluble decoy receptor precluding VEGFs and PlGF from binding to native VEGFR, and therefore preventing the emergence of resistance. Bevacizumab limits its function to preventing the interaction between VEGF-A and VEGFR. In combination with FOLFIRI (VELOUR trial), aflibercept improves survival in patients with metastatic CRC who are resistant or have progressed to oxaliplatin-based chemotherapy. Ramucirumab, a fully humanized immunoglobulin G1 (IgG-1) monoclonal antibody and regorafenib, a multikinase inhibitor, have significant improvement for overall survival as well as for progression-free survival in chemotherapy refractory settings.


Subject(s)
Colorectal Neoplasms/drug therapy , Placenta Growth Factor/antagonists & inhibitors , Angiogenesis Inhibitors/therapeutic use , Animals , Colorectal Neoplasms/metabolism , Drug Resistance, Neoplasm , Humans , Placenta Growth Factor/metabolism
14.
Breast Cancer Res Treat ; 162(1): 181-189, 2017 02.
Article in English | MEDLINE | ID: mdl-28040858

ABSTRACT

PURPOSE: In an era where neoadjuvant dual blockade is emerging as the standard of care for early and locally advanced HER2-positive breast cancer, we aimed to identify predictors of response to single-blockade chemotherapy. METHODS: This retrospective analysis reviewed all the incident stage I-III HER2-positive breast cancer patients who received neoadjuvant docetaxel, carboplatin, and trastuzumab (TCH) in three institutions. pCR was defined as the absence of invasive tumor in breast and axillary nodes (ypT0/isypN0). RESULTS: From 2008 to 2015, 84 patients receiving neoadjuvant TCH were identified within our institutions. The mean age at diagnosis was 51.8 years. 59.5% of the patients were hormone receptor (HR) positive, lymph node involvement occurred in 67.9%, and clinical distribution was 2.4, 65.5, and 32.1% for stage I, II, and III, respectively. pCR rate was 47.6%; there was a significantly lower response in HR-positive patients compared to HR-negative ones (34 vs 67.6%, p = 0.005). pCR rate was associated with tumor size, whereas differences did not reach significance either for stage or for nodal status. Multivariate analysis found that only HR status was associated with response (p = 0.003). At a median follow-up of 31.7 months, disease-free survival, distant disease-free survival, and overall survival were 78.6, 85.7, and 94%, respectively. Breast-conserving surgery was performed in 44% of the patients. Overall, TCH was well tolerated, with low rates of grade 3-4 adverse events, and neither late toxicities nor cardiac dysfunctions were reported. CONCLUSIONS: Neoadjuvant TCH, an anthracycline-free single-blockade regimen, achieved a pCR of 47.6%. Further molecular analyses are required in order to identify stronger predictive markers of pCR and thus for an accurate selection of patients who do not benefit from dual blockade.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biomarkers, Tumor , Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Carboplatin/administration & dosage , Docetaxel , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Receptor, ErbB-2/metabolism , Taxoids/administration & dosage , Trastuzumab/administration & dosage , Treatment Outcome , Young Adult
15.
BMJ Open ; 4(6): e005026, 2014 Jun 15.
Article in English | MEDLINE | ID: mdl-24934208

ABSTRACT

OBJECTIVES: To quantify the time spent by family physicians (FP) on tasks other than direct patient contact, to evaluate job satisfaction, to analyse the association between time spent on tasks and physician characteristics, the association between the number of tasks performed and physician characteristics and the association between time spent on tasks and job satisfaction. DESIGN: Cross-sectional, using time-and-motion techniques. Two workdays were documented by direct observation. A significance level of 0.05 was adopted. SETTING: Multicentric in 104 Portuguese family practices. PARTICIPANTS: A convenience sample of FP, with lists of over 1000 patients, teaching senior medical students and first-year family medicine residents in 2012, was obtained. Of the 217 FP invited to participate, 155 completed the study. MAIN OUTCOMES MEASURED: Time spent on tasks other than direct patient contact and on the performance of more than one task simultaneously, the number of direct patient contacts in the office, the number of indirect patient contacts, job satisfaction, demographic and professional characteristics associated with time spent on tasks and the number of different tasks performed, and the association between time spent on tasks and job satisfaction. RESULTS: FP (n=155) spent a mean of 143.6 min/day (95% CI 135.2 to 152.0) performing tasks such as prescription refills, teaching, meetings, management and communication with other professionals (33.4% of their workload). FP with larger patient lists spent less time on these tasks (p=0.002). Older FP (p=0.021) and those with larger lists (p=0.011) performed fewer tasks. The mean job satisfaction score was 3.5 (out of 5). No association was found between job satisfaction and time spent on tasks. CONCLUSIONS: FP spent one-third of their workday in coordinating care, teaching and managing. Time devoted to these tasks decreases with increasing list size and physician age.


Subject(s)
Family Practice , Job Satisfaction , Work , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Portugal , Time Factors
16.
Acta Med Port ; 18(1): 61-8, 2005.
Article in Portuguese | MEDLINE | ID: mdl-16202335

ABSTRACT

Interactions between physicians and detailers (even when legitimate ones) raise scientific and ethical questions. In Portugal little thinking and discussion has been done on the subject and the blames for bribery have monopolized the media. This work intended to review what has been said in medical literature about these interactions. How do physicians see themselves when interacting with pharmaceutical companies and their representatives? Do these companies in fact change their prescriptive behaviour, and, if so, how do they change it? How can physicians interact with detailers and still keep their best practice? A Medline research, from 1966 till 2002, was performed using the key-words as follows. A database similar to Medline but concerning medical journals published in Portugal, Index das Revistas Médicas Portuguesas, was also researched from 1992 to 2002. Pharmaceutical companies are profit bound and they allot promoting activities, and detailing in particular, huge amounts of money. Most physicians hold firmly to the belief that they are able to resist and not be influenced by drug companies promotion activities. Nevertheless, all previous works on literature tell us the opposite. Market research also indicates that detailers effectively promote drug sales. Various works also suggest that the information detailers provide to physicians may be largely incorrect, even comparing it to the written information provided by the pharmaceutical companies they work for. The frequency at which portuguese physicians (especially family physicians) contact with pharmaceutical sales representatives is higher than the frequency reported in countries where the available studies come from (namely, Canada and the United States of America). This may put portuguese physicians at a higher risk, making it imperative that work and wide debate are initiated among the class.


Subject(s)
Commerce/ethics , Drug Industry/ethics , Interprofessional Relations , Physicians/ethics
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