RESUMEN
Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/-25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inmunoterapia/métodos , Vértebras Lumbares/patología , Neoplasias Pulmonares/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Músculo Esquelético/patología , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/antagonistas & inhibidores , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Recuento de Células , Femenino , Estudios de Seguimiento , Humanos , Vértebras Lumbares/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Masculino , Melanoma/diagnóstico , Melanoma/mortalidad , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Tamaño de los Órganos , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios Retrospectivos , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/mortalidad , Análisis de Supervivencia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Several trials evaluated the role of intensive regimens, made of triplet chemotherapies plus bevacizumab, as first-line treatment for patients with metastatic colorectal cancer (mCRC). We previously reported, in a Phase II prospective study, the efficacy and the tolerability of FIrB/FOx regimen, reporting interesting results in terms of received dose intensities (rDIs) and safety. METHODS: We reported a retrospective update of 85 patients treated with FIrB/FOx, an intensive regimen of 5-fluorouracil, bevacizumab, and weekly alternate irinotecan and oxaliplatin, to confirm its feasibility in "real life". Subgroup analyses were performed, particularly among patients treated with standard and modified FIrB/FOx (based on age, performance status, and/or comorbidities). RESULTS: Overall, 3-month objective response rate (ORR) and 6-month ORR were 75.9% and 55.3%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were 14.4 and 34.9 months, respectively. Among the patients treated with standard and modified regimens, 3-month ORR, PFS, and OS were 75.8% and 76% (P=1.0000), 14.4 and 14.4 months (P=0.8589), and 37.8 and 26.6 months (P=0.7746), respectively. Among the K/NRAS wild-type and K/NRAS mutant patients, 3-month ORR, PFS, and OS were 95.2% and 74.5% (P=0.0526), 15.3 and 14.4 months (P=0.8753), and 37.8 and 51.4 months (P=0.8527), respectively. The rDIs were ≥80% of full doses both in the standard and in the modified regimens subgroups. Cumulative G3/4 toxicities were neutropenia (14.1%), diarrhea (17.6%), asthenia (9.4%), vomiting (5.6%), and hypertension (16.5%). CONCLUSION: This update shows that intensive regimens such as FIrB/FOx are also feasible options for first-line treatment of mCRC patients in the "real-life" setting.
RESUMEN
To date, there is no consensus regarding firstline chemotherapy for patients with HER2negative, locally advanced/metastatic gastric cancer (a/m GC). In the present study we reported a retrospective caseseries of patients treated with a weekly regimen containing timedflat infusion of 5fluorouracil (TFI/5FU), docetaxel and oxaliplatin. From June 2007 to July 2017, 32 consecutive a/m GC patients were treated with firstline standard (st) or modulated (mod) 'FD/FOx' regimen: Weekly 12 h (from 10.00 p.m. to 10.00 a.m.) TFI/5FU for two consecutive nights at 900 mg/m2/day, associated to weekly alternating docetaxel, 50 mg/m2 and oxaliplatin, 80 mg/m2. The median age of the patients was 60 years and their Eastern Cooperative Oncology Groupperformance status (ECOGPS) was as follows: i) ECOGPS 0/1, (n=28, 87.5%); and ii) ECOGPS 2 (n=4, 12.5%). Patient activity, efficacy and safety data were collected and subgroup analyses were conducted among patients treated with st and mod FD/FOx. In the intentiontotreat (ITT) analysis, the objective response rate (ORR) was 75% (95% CI, 5390) and the disease control rate (DCR) was 87.5% (95% CI, 67.697.3). After a median followup of 16 months, median progressionfree survival (PFS) and median overall survival (OS) were 14.0 and 19.0 months, respectively. The received doseintensities were ~80% of the standard doses for each agent. The most relevant treatmentrelated grade 3 adverse events were: Neutropenia (40.6%), asthenia (18.7%) and diarrhea (18.7%). The only treatmentrelated grade 4 adverse event was neutropenia (9.3%). No febrile neutropenia was observed and none of the patients died as a result of adverse events. FD/FOx regimen appeared to be a feasible option as a firstline treatment of a/m GC patients, especially in case of hightumor burden, with the need of rapid tumor shrinkage and diseaserelated symptoms palliation.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Neoplasias Gástricas/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Docetaxel , Esquema de Medicación , Unión Esofagogástrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxaliplatino , Estudios RetrospectivosRESUMEN
The most frequent site of recurrence in breast cancer (BC) is the bone, particularly in patients with 'luminal-like' disease. Denosumab has been shown to prevent aromatase inhibitors (AIs) induced bone resorption in postmenopausal early BC patients and reduce skeletal-related events (SREs) in bone metastatic breast cancer (BMBC). A 'real life' analysis of 90 BMBC patients treated with denosumab was performed. Eighty-six patients (95.6%) had 'luminal-like' disease, 72 (80%) had bone metastases at the time of first recurrence of disease. Among 50 patients with metachronous 'luminal-like' disease, 40 (80%) had first recurrence to the bone. Among these patients median time to skeletal recurrence (TSkR) was shorter for patients who were previously exposed to AIs compared to those who were not (53.0 vs. 102.0 months, respectively; P=0.0300) and longer for patients previously treated with tamoxifen compared to those who were not (102.0 vs. 59.0 months, respectively; P=0.0466). Both of them were not confirmed at multivariate analysis. In the overall population, 17 first SREs were observed (16 radiation therapy) and median time to first SRE was not reached. A statistically significant difference in the incidence of SREs was detected only between patients with exclusively osteolytic bone metastases vs. those without (P=0.013). The presence of exclusively-osteolytic bone metastases was the only factor significantly associated with a shorter time to first SRE (P=0.011). The only G3 toxicity reported was hypocalcemia in one patient. No osteonecrosis of the jaw events (ONJ) occurred. This study demonstrated that a pro-active attitude enables the treatment of the majority of patients with denosumab without significant class-related toxicities. The majority of SREs were from radiation therapy, so pain still remains the clinical hallmark of bone metastases, particularly for osteolytic ones. The suggestion that estrogen deprivation with AIs can favor a 'bone-related' risk conditions for developing bone metastases must be considered with caution and surely needs further validations.
RESUMEN
Cancer cells can alter physiological mechanisms within bone resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted therapy, as bisphosphonates and denosumab, are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. The toxicity profile is similar between bisphosphonates and denosumab, even if pyrexia, bone pain, arthralgia, renal failure and hypercalcemia are more common with bisphosphonates, while hypocalcemia and toothache are more frequently reported with denosumab. Osteonecrosis of the jaw (ONJ) occurred infrequently without statistically significant difference. The present review aims to provide an assessment on bone targeted therapies for preventing the occurrence of SREs in bone metastatic breast cancer patients, critically analyzing the evidence available so far on their effectiveness, in light of the different mechanisms of action. Thus, we try to provide tools for the most fitting treatment of bone metastatic breast cancer patients. We also provide an overview on the usefulness of bone turnover markers in clinical practice and new molecules currently under study for the treatment of bone metastatic disease.
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Neoplasias Óseas/prevención & control , Neoplasias Óseas/secundario , Huesos/patología , Neoplasias de la Mama/patología , Terapia Molecular Dirigida , Conservadores de la Densidad Ósea/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Remodelación Ósea , Neoplasias de la Mama/tratamiento farmacológico , Femenino , HumanosRESUMEN
Angiogenesis plays an essential role in the growth and progression of breast cancer. This observational single center study evaluated the efficacy and safety of a new weekly schedule of bevacizumab/paclitaxel combination in the first-line treatment of unselected, HER2-negative, metastatic breast cancer (MBC) patients, in a real-life setting. Thirty-five patients (median age 56 years, range 40-81) with HER2-negative MBC were treated with paclitaxel (70 mg/m(2) ) dd 1,8,15 q21 (60 mg/m(2) if ≥65 years or secondary Cumulative Illness Rating Scale) plus bevacizumab (10 mg/kg) every 2 weeks. Twenty-two patients (63%) had ≥2 metastatic sites and 15 (43%) visceral disease. Eleven patients (31%) had a triple-negative breast cancer (TNBC). A clinical complete response (cCR) was observed in 6 (17%) cases after a median of seven cycles, a partial response (PR) in 22 (63%), and a stable disease (SD) in 6 (17%) cases; the overall clinical benefit rate was 97%. In TNBC subgroup, cCR occurred in 1 (9%) case, PR in 8 (73%), and SD in 2 (18%). At a median follow-up of 13 months (range 1-79 months), the median progression-free survival was 11 months and the median overall survival was 36 months. No grade 4 adverse events occurred. The main grade 3 toxicities observed were neutropenia (11.4%), hypertension (5.7%), stomatitis (2.8%), diarrhea (2.8%), and vomiting (2.8%). The administration of weekly paclitaxel plus bevacizumab in this real-life experience shows similar efficacy than previously reported schedules, with a comparable dose intensity and a good toxicity profile.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Paclitaxel/administración & dosificación , Receptor ErbB-2/metabolismo , Resultado del TratamientoAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/secundario , Docetaxel , Femenino , Fluorouracilo/administración & dosificación , Humanos , Infusiones Intravenosas , Metástasis de la Neoplasia , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Intensive medical treatment increases resection rate of liver metastases in patients with metastatic colorectal cancer (MCRC). The effectiveness of liver metastasectomies was evaluated in patients with MCRC who were treated with previously reported FIr-B/FOx (triplet chemotherapy plus bevacizumab). PATIENTS AND METHODS: Fifty patients with MCRC enrolled in the reported phase II study were classified according to involved metastatic sites (liver-only metastatic site, multiple metastatic sites) and the extent of liver metastases (single, multiple). Surgical resectability of liver metastases was evaluated at baseline and every 3 cycles of FIr-B/FOx treatment. The resection rate of liver metastases, activity, and efficacy were evaluated; progression-free survival (PFS) and overall survival (OS) were compared by using the log-rank test. RESULTS: Patients with liver MCRC were 33 of 50 consecutive unselected patients with MCRC: liver limited, 22 patients; multiple metastatic sites, 11 patients. Liver metastasectomies were performed in 13 patients: 26% of 50 patients with MCRC, 39% of 33 patients with liver MCRC. In patients with liver-only MCRC, a secondary liver surgery was performed in 54%: 6 of 9 single and 6 of 13 multiple liver metastases. Also, 1 liver and lung metastasectomy was performed. Pathologic complete responses were achieved in 2 patients (15%). The conversion rate of unresectable liver metastases was 83%. Objective response rate, PFS, OS were, respectively: 84%, 11 and 23 months in 33 liver MCRC; 86%, 17 and 44 months in 22 liver-limited patients. PFS and OS were significantly increased in patients with liver-limited metastases compared with multiple metastatic sites and single compared with multiple liver metastases. CONCLUSION: The FIr-B/FOx regimen may increase the resection rate of liver metastases and improve clinical outcome of patients with liver-only MCRC.