Efficacy and safety of FOLFIRI/aflibercept (FA) in an elderly population with metastatic colorectal cancer (mCRC) after failure of an oxaliplatin-based regimen.

BACKGROUND: The VELOUR study showed the benefit of FOLFIRI-Aflibercept (FA) versus FOLFIRI in patients with metastatic colorectal cancer (mCRC) in second-line treatment. However, only 36% of the included patients were ≥65 years. Thus, we seek to evaluate the efficacy and safety of FA in the elderly population in the context of routine practice. MATERIALS AND METHODS: We conducted an observational, retrospective, multicenter, observational study of patients ≥70 years with mCRC treated with FA after progression to oxaliplatin chemotherapy in routine clinical practice in 9 hospitals of the GITuD group. RESULTS: Of 388 patients treated with FA between June 2013 and November 2018, 75 patients ≥70 years were included. The median number of cycles was 10 and the objective response (ORR) and disease control rates (DCR) were 33.8% and 72.0%, respectively. With a median follow-up of 27.1 months, median Progression-free survival (PFS) was 6.6 months and median Overall Survival (OS) was 15.1 months. One third fewer metastasectomies were performed in the ≥75 years' subgroup (24 vs. 52%, p = 0.024) and more initial FOLFIRI dose reductions (68 vs. 36%, p = 0.014). ORR (23.8% vs. 38.3%), DCR (42.8% vs. 85.1%), and PFS (4 vs. 7.8 months; p = 0.017) were significantly less, without difference in OS (9.9 vs. 17.1 months; p = 0.129). The presence of prior hypertension (HT) (PFS 7.9 vs. 5.7 months, p = 0.049) and HT ≥ grade 3 during treatment (PFS 7.6 vs. 6.6 months, p = 0.024) were associated with longer PFS. The most frequent grade 3/4 adverse events were: asthenia (21.3%), neutropenia (14.7%), and diarrhea (14.7%). 57.3% required FOLFIRI dose reduction; 34.7% of aflibercept, including discontinuation (5.3% and 18.7%, respectively). CONCLUSIONS: FA combination is effective in patients ≥70 years. The occurrence of HT is predictive of efficacy. Close monitoring of toxicity and initial dose adjustment is recommended.

Venous Thromboembolism In Cancer Patients: "From Evidence to Care".

This article seeks to review the current status of treatment and prevention of venous thromboembolic disease (VTE) in cancer patients after the addition of direct oral anticoagulants (DOAC) to the therapeutic arsenal available. The suitability of DOAC use in complex clinical situations, poorly represented in clinical trials, is controversial and difficult for care activity, making the recommendations in clinical practice guidelines the focus of special attention in this area. Recently, several randomized trials have compared low molecular weight heparin (LMWH) to DOAC for the management of CAT. Potential drug interactions with DOACs or the increased risk of bleeding in intraluminal tumors require special precautions, as do metastatic or primary brain disease and comorbid conditions, such as renal or liver failure, which are not suitably represented in pivotal studies. Furthermore, few data are available for situations involving elevated bleeding risk, with thrombocytopenia levels below the inclusion criterion of clinical trials, or recurrence during active anticoagulant therapy. Similarly, it is less clear that patients and physicians accept the presumption that oral DOAC administration is more convenient than subcutaneous LMWH, particularly when drug absorption may be compromised. The non-inclusion or under-representation of patients at higher risk for complications with anticoagulation in randomized clinical trials, makes their use complex in certain situations in health care. This paper provides a practical review of current clinical guideline recommendations regarding LMWH and/ or DOAC to treat and prevent CAT, as well as the most controversial clinical conditions for their use.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Prediction of survival in patients with advanced, refractory colorectal cancer in treatment with trifluridine/tipiracil: real-world vs clinical trial data.

Trifluridine/tipiracil increases overall survival (OS) in patients with refractory, metastatic colorectal cancer (mCRC). A post hoc exploratory analysis of the RECOURSE randomized clinical trial (RCT) established two categories, a good prognosis corresponding to subjects having a low tumor burden and indolent disease. Other models in refractory mCRC are the FAS-CORRECT and Colon Life nomogram. The main objective was to externally validate the prognostic factors of the RECOURSE and FAS-CORRECT trials, and the Colon Life nomogram in a multicenter, real-world series of mCRC treated in 3rd and successive lines with trifluridine/tipiracil. The secondary aim was to develop an OS predictive model, TAS-RECOSMO. Between 2016 and 2019, 244 patients were recruited. Median OS was 8.15 vs 8.12 months for the poor (85% of the subjects) and good (15%) prognosis groups from the RESOURCE trial, respectively, log-rank p = 0.9. The most common grade 3-4 toxicities were neutropenia (17%), asthenia (6%), and anemia (5%). The AFT lognormal model TAS-RECOSMO included six variables: ECOG-PS, KRAS/NRAS/BRAF mutation status, time between diagnosis of metastasis and beginning of trifluridine/tipiracil, NLR, CEA, and alkaline phosphatase. The model's bootstrapped bias-corrected c-index was 0.682 (95% CI, 0.636-0.722). The factors from the Colon Life model, FAS-CORRECT, and RECOURSE displayed a c-index of 0.690, 0.630, and 0.507, respectively. TAS-RECOSMO, FAS-CORRECT, and the Colon Life nomogram appear to predict OS in patients with refractory mCCR who begin trifluridine/tipiracil treatment in the real world. The prognostic groups of the RECOURCE RCT were unable to capture the situation of real-world subjects treated with trifluridine/tipiracil in this series.

Effect of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF v600-mutated metastatic colorectal cancer: a real-world study in Spain.

BACKGROUND: Outcomes are poorer in metastatic colorectal cancer (mCRC) patients with BRAF V600E mutations than those without it, but the effect of these mutations on treatment response is unclear. This real-world study assessed the effects of antiangiogenic-based treatment and systemic inflammatory factors on outcomes in patients with BRAF V600-mutated mCRC. METHODS: This real-world, multicenter, retrospective, observational study included patients with BRAF V600-mutated mCRC treated in eight hospitals in Spain. The primary endpoints were overall survival (OS) and progression-free survival (PFS); overall response rate (ORR) and disease control rate (DCR) were also assessed. The effect of first- and second-line treatment type on OS, PFS, ORR, and DCR were evaluated, plus the impact of systemic inflammatory markers on these outcomes. A systemic inflammation score (SIS) of 1-3 was assigned based on one point each for platelet-lymphocyte ratio (PLR) ≥200, neutrophil-lymphocyte ratio (NLR) ≥3, and serum albumin < 3.6 g/dL. RESULTS: Of 72 patients, data from 64 were analyzed. After a median of 69.1 months, median OS was 11.9 months and median first-line PFS was 4.4 months. First-line treatment was triplet chemotherapy-antiangiogenic (12.5%), doublet chemotherapy-antiangiogenic (47.2%), doublet chemotherapy-anti-EGFR (11.1%), or doublet chemotherapy (18.1%). Although first-line treatment showed no significant effect on OS, antiangiogenic-based regimens were associated with prolonged median PFS versus non-antiangiogenic regimens. Negative predictors of survival with antiangiogenic-based treatment were NLR, serum albumin, and SIS 1-3, but not PLR. Patients with SIS 1-3 showed significantly prolonged PFS with antiangiogenic-based treatment versus non-antiangiogenic-based treatment, while those with SIS=0 showed no PFS benefit. CONCLUSIONS: Antiangiogenic-based regimens, SIS, NLR, and albumin were predictors of survival in patients with mCRC, while SIS, NLR and serum albumin may predict response to antiangiogenic-based chemotherapy. TRIAL REGISTRATION: GIT-BRAF-2017-01.

First-line panitumumab plus capecitabine for the treatment of older patients with wild-type RAS metastatic colorectal cancer. The phase II, PANEL study.

BACKGROUND: Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type [WT] RAS mCRC. PATIENTS AND METHODS: Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1-14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 [26%], 1 [67%], 2 [7%]) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7-63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5-10.4) months, and median TTR was 2.2 (1.9-2.8) months. Median TTP was 9.6 (4.8-11.5) months, with a median TTF of 5.2 (2.8-7.2) months. The median PFS was 7.5 (4.4-10.4) months, and the median OS was 23.7 (7.4-27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3-4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related. CONCLUSION: This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC.

[Anthropometric parameters in evaluating malnutrition in oncological patients; utility of body mass index and percentage of weight loss]. / Parámetros antropométricos en la evaluación de la malnutrición en pacientes oncológicos hospitalizados; utilidad del índice de masa corporal y del porcentaje de pérdida de peso.

OBJECTIVE: To compare the BMI and the percentage of weight loss as markers for malnutrition in hospitalized cancer patients considering the Patient-Generated Global Subjective Assessment (PG-GSA) as the gold standard. METHOD: Cross-sectional descriptive study in patients admitted to the Medical Oncology Department of the Hospital Xeral de Vigo, from May to September of 2011. RESULTS: 28 patients (15 males). Mean age 63.46 years ± 11.05. Mean BMI 23.75 kg/m² ± 3.62. Mean percentage of weight loss 8.53% ± 6.20. In group A (well nourished) the percentage of weight loss was 1.07 ± 1.85, in group B (moderately malnourished) 7.90 ± 1.73, and in group C (severely malnourished) 10.91 ± 6.91 (p = 0.034). The BMI showed no statistically significant differences. CONCLUSIONS: The BMI is not a proper parameter todetect malnutrition, by contrast with the percentage of weight loss that did show a direct association with the degree of hyponutrition.

Objetivo: Comparar el IMC y el porcentaje de pérdida de peso como marcadores de malnutrición en el paciente oncológico hospitalizado tomando como referencia la Valoración Subjetiva Global Generada por el Paciente (VSG-GP). Método: Estudio descriptivo transversal en pacientes ingresados en Oncología Médica del Hospital Xeral de Vigo de mayo a septiembre de 2011. Resultados: 28 pacientes (15 varones). Edad media 63,46 años ± 11,05. IMC medio 23,75 kg/m2 ± 3,62. Porcentaje medio de pérdida de peso 8,53% ± 6,20. En el grupo A (bien nutridos) el porcentaje de pérdida de peso fue de 1,07 ± 1,85, en el B (moderadamente desnutridos) de 7,90 ± 1,73 y en el C (severamente desnutridos) 10,91 ± 6,91 (p = 0,034). El IMC no obtuvo diferencias estadísticamente significativas. Conclusiones: El IMC no es un parámetro adecuado para detectar malnutrición a diferencia del porcentaje de pérdida de peso que sí mostró una asociación directa con el grado de desnutrición.

Parámetros antropométricos en la evaluación de la malnutriciónen pacientes oncológicos hospitalizados; utilidad del índice de masacorporal y del porcentaje de pérdida de peso / Anthropometry parameters in evaluating malnutrition in oncological patients; utility of body mass index and percentage of weight loss

Objetivo: Comparar el IMC y el porcentaje de pérdida de peso como marcadores de malnutrición en el paciente oncológico hospitalizado tomando como referencia la Valoración Subjetiva Global Generada por el Paciente (VSG-GP). Método: Estudio descriptivo transversal en pacientes ingresados en Oncología Médica del Hospital Xeral de Vigo de mayo a septiembre de 2011. Resultados: 28 pacientes (15 varones). Edad media 63,46 años ± 11,05. IMC medio 23,75 kg/m2 ± 3,62. Porcentaje medio de pérdida de peso 8,53% ± 6,20. En el grupo A (bien nutridos) el porcentaje de pérdida de peso fue de 1,07 ± 1,85, en el B (moderadamente desnutridos) de 7,90 ± 1,73 y en el C (severamente desnutridos) 10,91 ± 6,91 (p = 0,034). El IMC no obtuvo diferencias estadísticamente significativas. Conclusiones: El IMC no es un parámetro adecuado para detectar malnutrición a diferencia del porcentaje de pérdida de peso que sí mostró una asociación directa con el grado de desnutrición (AU)

OBJECTIVE: To compare the BMI and the percentage of weight loss as markers for malnutrition in hospitalized cancer patients considering the Patient-Generated Global Subjective Assessment (PG-GSA) as the gold standard. METHOD: Cross-sectional descriptive study in patients admitted to the Medical Oncology Department of the Hospital Xeral de Vigo, from May to September of 2011.RESULTS:28 patients (15 males). Mean age 63.46 years ± 11.05. Mean BMI 23.75 kg/m² ± 3.62. Mean percentage of weight loss 8.53% ± 6.20. In group A (well nourished) the percentage of weight loss was 1.07 ± 1.85, in group B (moderately malnourished) 7.90 ± 1.73, and in group C (severely malnourished) 10.91 ± 6.91 (p = 0.034). The BMI showed no statistically significant differences. CONCLUSIONS: The BMI is not a proper parameter to detect malnutrition, by contrast with the percentage of weight loss that did show a direct association with the degree of hyponutrition (AU)

Megestrol acetate-induced adrenal insufficiency.

Megestrol acetate is a synthetic progestin that has been used since the 1970s for the treatment of advanced cancer and subsequently to treat anorexia, cachexia and weight loss in AIDS patients. It has been shown that high doses or prolonged treatment with this drug may cause Cushing's syndrome, new-onset diabetes and suppression of plasma ACTH and cortisol levels. Megestrol acetate may cause suppression of the pituitary-adrenal axis due to the affinity of this compound for the glucocorticoid receptor. Recognising the glucocorticoid-like activity of megestrol and its effects at the axis level is important for the diagnosis of sub-clinical adrenal insufficiency. We present the case of a 74-year-old woman with infiltrating ductal breast carcinoma refractory to prolonged hormonal treatment with megestrol acetate, presenting with adrenal insufficiency.