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Simple and accessible prognostic factors are paramount for solid cancer patients experiencing life-threatening complications. The aim of this study is to appraise the impact of functional and nutritional status and skeletal muscle mass in this population. We conducted a retrospective (2007−2020) single-center study by enrolling adult patients with solid cancers requiring unplanned ICU admission. Performance status, body weight, and albumin level were collected at ICU admission and over six months. Skeletal muscle mass was assessed at ICU admission by measuring muscle areas normalized by height (SMI). Four-hundred and sixty-two patients were analyzed, mainly with gastro-intestinal (34.8%) and lung (29.9%) neoplasms. Moreover, 92.8% of men and 67.3% of women were deemed cachectic. In the multivariate analysis, performance status at ICU admission (CSH 1.74 [1.27−2.39], p < 0.001) and the six month increase in albumin level (CSH 0.38 [0.16−0.87], p = 0.02) were independent predictors of ICU mortality. In the subgroup of mechanically ventilated patients, the psoas SMI was independently associated with ICU mortality (CSH 0.82 [0.67−0.98], p = 0.04). Among the 368 ICU-survivors, the performance status at ICU admission (CSH 1.34 [1.14−1.59], p < 0.001) and the six-month weight loss (CSH 1.33 [1.17−2.99], p = 0.01) were associated with a one-year mortality rate. Most cancer patients displayed cachexia at ICU admission. Time courses of nutritional parameters may aid the prediction of short- and long-term outcomes.
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Background: Nivolumab improved patients' survival in metastatic renal cell carcinoma (mRCC). We aimed to evaluate resting energy expenditure (REE) (i.e., patients' basal metabolism) to predict efficacy. Methods: We conducted a monocentric, observational study of mRCC patients receiving nivolumab between October 2015 and May 2020. REE was measured prior to initiating immunotherapy using indirect calorimetry to determine hypo, normo and hypermetabolism. Primary endpoint was 6-month, progression-free survival (PFS), and secondary endpoints were response rate, PFS and overall survival (OS). Results: Of the 51 consecutive patients, 15 (29%) were hypermetabolic, 24 (47%) normometabolic, and 12 (24%) hypometabolic. The 6-month PFS was 15% for hypermetabolic patients and 65% for non-hypermetabolic patients (p < 0.01). In the multivariate analysis, hypermetabolism was the only baseline factor predicting 6-month PFS (OR 9.91, 95%CI [1.62−60.55], p = 0.01). Disease progression was noted as the best response in 73% of hypermetabolic patients and 26% of non-hypermetabolic patients (p = 0.02). Median PFS was 2.8 and 8.7 months (p < 0.01), and median OS was 20.2 and 35.1 months (p = 0.13) in the hypermetabolic and non-hypermetabolic groups, respectively. Conclusions: Our study identifies an association between mRCC patients' energy expenditure and nivolumab efficacy. The measurement of REE by indirect calorimetry in routine practice could help identify patients at risk of nivolumab failure.
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BACKGROUND: The risk of drug-drug interactions (DDI) has become a major issue in cancer patients. However, data in sarcoma patients are scarce. We aimed to evaluate the frequency and the factors associated with DDI with antitumor treatments, and to evaluate the impact of a pharmacist evaluation before anticancer treatment. PATIENTS AND METHODS: We performed a retrospective review of consecutive sarcoma patients starting chemotherapy (CT) or Tyrosine kinase inhibitor (TKI). A pharmacist performed medication reconciliation and established an early toxicity risk assessment. Potential DDI with antitumor drugs were identified using Micromedex electronic software. RESULTS: One hundred and twenty-two soft-tissue and 80 bone sarcoma patients (103 males, median age 50 years,) were included before CT (86%) or TKI (14%). The median number of medications was 3; 34 patients (22% of patients with medication reconciliation) reported complementary medicine use. 37 potential DDI classified as major, were identified (12% of the 243 pre-therapeutic assessments). In multivariate analysis, TKI (p < 0.0001), proton pump inhibitor (p = 0.026) and antidepressant (p < 0.001) were identified as risk factors of DDI (p < 0.02). Only marital status (p = 0.003) was associated with complementary medicine use. A pharmacist performed 157 medication reconciliations and made 71 interventions among 59 patients (37%). In multivariate analysis, factors associated with pharmacist intervention were: complementary medicines (p = 0.004), drugs number (p = 0.005) and treatment with TKI (p = 0.0002) CONCLUSIONS: Clinical interventions on DDI are more frequently required among sarcoma patients treated with TKI than CT. Multidisciplinary risk assessment including a medication reconciliation by a pharmacist could be crucial to prevent DDI with TKI.
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Antineoplásicos/administração & dosagem , Farmacêuticos/organização & administração , Sarcoma/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Interações Medicamentosas , Feminino , Humanos , Masculino , Reconciliação de Medicamentos/métodos , Pessoa de Meia-Idade , Assistência Farmacêutica/organização & administração , Papel Profissional , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Gestão de Riscos/métodos , Sarcoma/patologia , Neoplasias de Tecidos Moles/tratamento farmacológico , Neoplasias de Tecidos Moles/patologiaRESUMO
BACKGROUND & AIMS: Alterations of nutritional and performance status (PS) are associated with higher risk of chemotherapy toxicity. Increased resting energy expenditure (REE) is frequent in cancer patients and may contribute to cachexia. We investigated whether abnormal energetic metabolism could predict early acute limiting toxicities (ELT) of anticancer treatments. METHODS: In this observational monocentric study, REE was measured by indirect calorimetry before treatment initiation. Based on the ratio of measured REE to REE predicted by the Harris-Benedict formula, patients were classified as hypometabolic (<90%), normometabolic (90-110%) or hypermetabolic (>110%). Body mass index, weight loss, PS, albumin, transthyretin, C-reactive protein (CRP) and muscle mass (CT-scan) were studied. Were defined as ELT any unplanned hospitalization or any adverse event leading to dose reduction or discontinuation during the first cycle of treatment. RESULTS: We enrolled 277 patients: 76% had metastatic disease; 89% received chemotherapy and 11% targeted therapy; 29% were normometabolic, 51% hypermetabolic and 20% hypometabolic. Fifty-nine patients (21%) experienced an ELT. Toxicity was associated with abnormal metabolism (vs normal: OR = 2.37 [1.13-4.94], p = 0.023), PS (2-3 vs 0-1: OR = 2.04 [1.12-3.74], p = 0.023), albumin (<35 vs ≥35 g/l: OR = 2.39 [1.03-5.54], p = 0.048), and inflammation (CRP ≥10 vs <10 mg/l: OR = 2.43 [1.35-4.38], p = 0.004). To predict toxicity, the most sensitive parameter was the REE (83%) followed by PINI (63%), GPS (59%), CRP (55%), PS (41%), NRI (37%), and albumin (16%). In multivariate analysis, elevated CRP was an independent predictor of toxicity (p = 0.047). CONCLUSION: Abnormal basal energy metabolism identifies patients at higher risk of treatment-related acute complications.
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Metabolismo Basal/fisiologia , Caquexia/complicações , Caquexia/diagnóstico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Caquexia/fisiopatologia , Calorimetria Indireta , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Descanso , Medição de RiscoAssuntos
Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição/tratamento farmacológico , Citidina Desaminase/sangue , Desoxicitidina/análogos & derivados , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Biomarcadores Tumorais/análise , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Desoxicitidina/efeitos adversos , Desoxicitidina/metabolismo , Humanos , Masculino , GencitabinaRESUMO
Angiogenesis inhibition is a major antitumor strategy that has emerged during the last decade. Oral tyrosine kinase inhibitors (TKI) targeting the VEGF receptor, including sunitinib, sorafenib, axitinib, regorafenib, pazopanib, and vandetanib reduce tumor growth and metastasis. These agents are approved for the treatment of metastatic diseases in first or second-line. They display a narrow therapeutic index. However, data in the elderly and/or in patients with multiple illnesses remain scarce. This population is classically excluded from clinical trials. The aim of this review is to provide an overview of existing literature regarding antiangiogenic TKI tolerance in the elderly (>70 years old). We also highlight key points of the pre-therapeutic evaluation and summarize the management of common toxicities.
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Inibidores da Angiogênese/efeitos adversos , Neovascularização Patológica/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Idoso , Idoso de 80 Anos ou mais , Axitinibe , Fadiga/induzido quimicamente , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Indóis/efeitos adversos , Rim/efeitos dos fármacos , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Piperidinas/efeitos adversos , Piridinas/efeitos adversos , Pirróis/efeitos adversos , Quinazolinas/efeitos adversos , Sorafenibe , SunitinibeRESUMO
PURPOSE: Pegylated liposomal doxorubicin (PLD) is widely used in relapsing ovarian carcinoma. Its original formulation is metabolized by the monocyte-macrophage system. One of its main toxicities is the palmoplantar erythrodysesthesia (PPE) syndrome. To date, no predictive factors of PPE have been identified. METHODS: Data of patients (pts) treated with PLD between 2005 and 2014 were retrospectively collected. A case-control study was performed, comparing main baseline clinical and biological characteristics of pts experiencing PPE and those who did not, after at least three cycles of PLD. A pilot analysis of blood monocyte subpopulations (classical, intermediate and non-classical) was performed by FACS in selected pts. RESULTS: Among 88 pts treated with PLD, 28 experienced PPE of any grade (31, 95 % CI 21-41). The first occurrence of PPE was at first cycle in only 11 % of pts, peaked at cycle 2 (32 %) and represented 57 % of cases after cycle 3. Baseline characteristics of pts with PPE were compared to 27 control pts who received at least 3 cycles. Older pts represented 61 % of pts with PPE and 15 % of pts without PPE (p = 0.04 by Chi-square test). Monocyte count and inflammatory parameters were not associated with PPE. However, the analysis of monocyte subpopulations revealed a large inter-patient variability. CONCLUSION: Contrary to most acute toxicities, PPE occurred more frequently after several cycles, suggesting a PLD body accumulation through repeated cycles. PPE was more frequent in pts older than 70 years. Monocyte subpopulations may have different roles on PLD metabolism and warrant further studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma/tratamento farmacológico , Doxorrubicina/análogos & derivados , Síndrome Mão-Pé/etiologia , Monócitos/efeitos dos fármacos , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/efeitos adversos , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Estudos de Casos e Controles , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Projetos Piloto , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/uso terapêutico , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Estomatite/induzido quimicamente , Neoplasias do Timo/tratamento farmacológico , Adulto JovemRESUMO
INTRODUCTION: Sorafenib is a multi-tyrosine kinase inhibitor (TKI). Considerable clinical experience has been accumulated since its first Phase III clinical trial in metastatic renal cancer patients in 2007. The management of its early acute toxicity in fit patients is well known. The management of prolonged treatment becomes the new challenge. AREAS COVERED: Using sorafenib as a key word for PubMed search, we review preclinical and clinical data and discuss the pharmacokinetics and pharmacodynamics of sorafenib, its acute and cumulative toxicities and their consequences for patient management. EXPERT OPINION: The systematic multi-disciplinary risk assessment of cancer patients prior to TKI initiation reduces the risks of acute and late toxicity, especially drug-drug interactions and arterial risks. Sarcopenia is now identified as a major risk of severe toxicity. The very diverse clinical pictures of cumulative toxicity must be known. The monitoring of sorafenib systemic exposure is helpful especially in elderly patients. Moreover, at disease progression, it allows distinguishing between underexposure to sorafenib and truly acquired resistance to the drug. The optimal use of sorafenib should allow improving the reported results of flat-dose. Finally, most of this knowledge could be used for the development and optimal use of the other TKIs.
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Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Administração de Caso , Interações Medicamentosas , Humanos , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/farmacocinética , Niacinamida/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/farmacocinética , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacocinética , Medição de Risco , SorafenibeRESUMO
PURPOSE: Ambulatory chemotherapy is patient friendly but may result in toxicity-induced unscheduled hospitalizations (TIUHs). This emerging issue may increase health care costs. We studied the cost effectiveness of a hospital-home monitoring program based on systematic iterative telephone calls after chemotherapy. PATIENTS AND METHODS: We retrospectively evaluated the rates of chemotherapy-induced unscheduled hospitalizations in patients who were treated in August 2008. Patients were contacted by telephone 1 day before chemotherapy and on the second and eighth days after undergoing chemotherapy. Costs associated with TIUHs were calculated and compared with those of a cohort concomitantly treated using the standard follow-up procedure. RESULTS: A total of 259 patients entered the hospital-home monitoring program. They were compared with 86 patients who had similar characteristics but underwent the standard treatment and follow-up procedure. Inclusion in the hospital-home monitoring program resulted in patients experiencing TIUHs approximately half as frequently as patients in the other group (2.4% v 4.9%; P < .01). Patients in the program experienced TIUHs for a median length of stay of 4 days, representing a nonsignificant reduction in duration of hospitalization (P not significant). Consequently, through a two-fold reduction in TIUH annual incidence, this program represents a reduction in unscheduled hospitalizations per year of 383 days, decreasing hospital costs by 201.468 ($292,468) per year. CONCLUSION: The hospital-home monitoring program is a cost-effective strategy for offering ambulatory chemotherapy treatment to patients with cancer. This program has become our standard procedure for ambulatory chemotherapy in patients with cancer.