RESUMEN
BACKGROUND: Patient-reported outcomes (PROs) are validated tools to assess the impact of efficacy and toxicities of cancer treatments on patients' health status. Because of the demonstrated little reliability of humans in reporting memories of painful experiences, this work explores the reliability of cancer patients in reporting chemotherapy-related toxicities. AIM: This study aims to evaluate the concordance between toxicities experienced by the patients during chemotherapy and toxicities reported to the doctor at the end of the cycles. METHODS: Questionnaires concerning chemotherapy-related toxicities were administered on days 2, 5, 8, 11, 14, and 17 of each chemo cycle and at the end of the same cycle to patients undergoing adjuvant chemotherapy. The co-primary end-points were Lins's concordance correlation coefficient (CCC) and mean difference between real-time and retrospective toxicity assessments. RESULTS: In total, 7182 toxicity assessments were collected from 1096 questionnaires. Concordance was observed between the retrospective evaluations and the toxicity assessments at early (day 2), peak (maximum toxicity), late (day 14 or 17), and mean real-time evaluations for each chemotherapy cycle (CCC for mean ranging from 0.52 to 0.77). No systematic discrepancy was found between real-time and retrospective evaluations, except for peak, which was systematically underestimated retrospectively. CONCLUSIONS: Toxicities reported by the patients to the doctor at the end of each chemotherapy cycle reflect what they actually experienced without any substantial distortion. This result is very relevant both for the clinical implications in daily patients' management and in the light of the current growing impact on digital monitoring of PROs.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Medición de Resultados Informados por el Paciente , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Quimioterapia Adyuvante/efectos adversos , Encuestas y Cuestionarios , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
BACKGROUND: the APICE study evaluates the cost-effectiveness of nanoparticle albumin-bound paclitaxel (nab-paclitaxel - Nab-P) + gemcitabine (G) vs G alone in metastatic pancreatic cancer (MPC) from the Italian National Health Service (INHS) standpoint. RESEARCH DESIGN AND METHODS: A 4-year, 4 health states (progression-free; progressed; end of life; death) Markov model based on the MPACT trial was developed to estimate costs (Euro [], 2017 values), and quality-adjusted life years (QALYs). Patients were assumed to receive intravenously Nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 every 4 weeks or G alone 1000 mg/m2 weekly for 7 out of 8 weeks (cycle 1) and then on days 1, 8, and 15 every 4 weeks (cycle 2 and subsequent cycles) until progression. One-way and probabilistic sensitivity analyses explored the uncertainty surrounding the baseline incremental cost-utility ratio (ICUR). RESULTS: Nab-P + G totals 0.154 incremental QALYs and 7082.68 incremental costs vs G alone. ICUR (46,021.58) is lower than the informal threshold value of 87,330 adopted by the Italian Medicines Agency during 2010-2013 for reimbursing oncological drugs. Sensitivity analyses confirmed the robustness of the baseline findings. CONCLUSIONS: Nab-P + G in MPC patients can be considered cost-effective for the INHS.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Años de Vida Ajustados por Calidad de Vida , Albúminas/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Análisis Costo-Beneficio , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Humanos , Italia , Cadenas de Markov , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Neoplasias Pancreáticas/patología , GemcitabinaRESUMEN
Although lactate dehydrogenase (LDH) serum levels, indirect markers of angiogenesis, are associated with a worse outcome in several tumours, their prognostic value is not defined in pancreatic cancer. Moreover, high levels are associated even with a lack of efficacy of tyrosine kinase inhibitors, contributing to explain negative results in clinical trials. We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib. Seventy-one of 114 patients included in the randomised phase II trial MAPS (chemotherapy plus or not sorafenib) and with available serum LDH levels, were included in this analysis. Patients were categorized according to serum LDH levels (LDH ≤ vs.> upper normal rate). A significant difference was found in progression free survival (PFS) and in overall survival (OS) between patients with LDH values under or above the cut-off (PFS: 5.2 vs. 2.7 months, p = 0.0287; OS: 10.7 vs. 5.9 months, p = 0.0021). After stratification according to LDH serum levels and sorafenib treatment, patients with low LDH serum levels treated with sorafenib showed an advantage in PFS (p = 0.05) and OS (p = 0.0012). LDH appears to be a reliable parameter to assess the prognosis of advanced pancreatic cancer patients, and it may be a predictive parameter to select patients candidate to receive sorafenib.
Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , L-Lactato Deshidrogenasa/sangre , Niacinamida/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Niacinamida/uso terapéutico , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/enzimología , Pronóstico , SorafenibRESUMEN
BACKGROUND: The RAF-MEK-ERK pathway is commonly activated in pancreatic cancer because of a high frequency of KRAS-BRAF mutations. A phase II randomized trial was designed to investigate the activity of sorafenib in combination with chemotherapy in advanced pancreatic cancer. METHODS: Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B). RESULTS: One hundred and fourteen patients were enrolled; of these, 43 (74.6%) patients progressed in arm A and 44 (82.4%) in arm B. Median progression-free survival was 4.3 months (95% CI: 2.7-6.5) and 4.5 months (95% CI: 2.5-5.2), respectively (HR=0.92; 95% CI: 0.62-1.35). Median overall survival was 7.5 (95% CI: 5.6-9.7) and 8.3 months (95% CI: 6.2-8.7), respectively (HR=0.95; 95% CI: 0.62-1.48). Response rates were 3.4% in arm A and 3.6% in arm B. CONCLUSIONS: Sorafenib does not significantly enhance activity of chemotherapy in advanced pancreatic cancer patients, and therefore should not be assessed in phase III trials.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Cisplatino/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Neoplasias Pancreáticas/patología , Compuestos de Fenilurea/administración & dosificación , Sorafenib , Resultado del Tratamiento , GemcitabinaRESUMEN
BACKGROUND: NGR-hTNF consists of human tumour necrosis factor (hTNF) fused with the tumour-homing peptide Asp-Gly-Arg (NGR), which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels. Preclinical antitumour activity was observed even at low doses. We evaluated the activity and safety of low-dose NGR-hTNF in colorectal cancer (CRC) patients failing standard therapies. PATIENTS AND METHODS: Thirty-three patients with progressive disease at study entry received NGR-hTNF 0.8 µg/m(2) given intravenously every 3 weeks. The median number of prior treatment regimens was three (range, 2-5). One-quarter of patients had previously received four or more regimens and two-thirds targeted agents. Progression-free survival (PFS) was the primary study objective. RESULTS: NGR-hTNF was well tolerated. No treatment-related grade 3 to 4 toxicities were detected, most common grade 1 to 2 adverse events being short-lived, infusion-time related chills (50.0%). One partial response and 12 stable diseases were observed, yielding a disease control rate of 39.4% (95% CI, 22.9-57.8%). Median PFS and overall survival were 2.5 months (95% CI, 2.1-2.8) and 13.1 months (95% CI, 8.9-17.3), respectively; whereas in patients who achieved disease control the median PFS and overall survival were 3.8 and 15.4 months, respectively. In an additional cohort of 13 patients treated at same dose with a weekly schedule, there was no increased toxicity and 2 patients experienced PFS longer than 10 months. CONCLUSION: Based on tolerability and preliminary evidence of disease control in heavily pretreated CRC patients, NGR-hTNF deserves further evaluation in combination with standard chemotherapy.
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Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Proteínas Recombinantes de Fusión/administración & dosificación , Factor de Necrosis Tumoral alfa/administración & dosificación , Anciano , Antineoplásicos/efectos adversos , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas Recombinantes de Fusión/efectos adversos , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/efectos adversosRESUMEN
To evaluate the safety and efficacy of infliximab administered with gemcitabine to treat cancer cachexia and to explore a functional measure of clinical benefit, investigators involved in this multicenter, phase II, placebo-controlled study randomized 89 patients with stage II-IV pancreatic cancer and cachexia to receive either placebo or 3 mg/ kg or 5 mg/kg of infliximab at weeks 0, 2, and 4 and then every 4 weeks to week 24; patients also received 1,000 mg/m2 of gemcitabine weekly from weeks 0-6 and then for 3 of every 4 weeks until their disease progressed. The primary endpoint was change in lean body mass (LBM) at 8 weeks from baseline; major secondary endpoints included overall survival, progression-free survival, Karnofsky performance status, and 6-minute walk test distance. In addition, quality of life was measured. The mean change in LBM at 8 weeks was +0.4 kg for patients receiving placebo, +0.3 kg for those receiving 3 mg/kg of infliximab, and +1.7 kg for those receiving 5 mg/kg of infliximab. No statistically significant differences in LBM or secondary endpoints were observed among the groups. Safety findings were similar in all groups. Adding infliximab to gemcitabine to treat cachexia in advanced pancreatic cancer patients was not associated with statistically significant differences in safety or efficacy when compared with placebo.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Caquexia/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/administración & dosificación , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Infliximab , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Masculino , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Placebos , Pronóstico , Tasa de Supervivencia , GemcitabinaRESUMEN
Angiogenesis is essential for tumor growth and metastasis, and has become a useful target for novel biological agents. Vascular endothelial growth factor (VEGF) is one of the most important angiogenesis regulators. Bevacizumab is a recombinant humanized anti-VEGF monoclonal antibody recently approved in Europe and the USA for first- and second-line therapy (in combination with chemotherapy) for metastatic colorectal cancer. It has a proven impact on survival, as demonstrated in large Phase III clinical trials. Treatment with bevacizumab is generally well tolerated, with hypertension and arterial thromboembolic events being the main side effects. Currently, its role in the adjuvant setting, in combination with chemotherapy, is being evaluated in large Phase III clinical trials.
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Anticuerpos Monoclonales/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/farmacocinética , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacosRESUMEN
Gastric cancer is a major clinical challenge, with poor overall prognosis and limited life expectancy for patients with advanced disease. Even with surgery and other modalities, palliation is often difficult. Improvement of response rates has evolved with the development of standard regimens and those incorporating newer chemotherapy agents, such as oral fluoropyrimidines, the taxanes, camptothecins, novel platinums (eg, oxaliplatin [Eloxatin]), and antifolates (eg, pemetrexed [Alimta]). Ongoing trials with these regimens aim toward improving survival, as well as improving the safety profile. It is hoped that in conjunction with molecular research in the pathogenesis of gastric cancer and development of targeted therapies in this disease, these trial data might lead to the evolution of treatment strategies that could prove effective.