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Data on octogenarian patients with MM are scarce, and optimal management remains controversial. We report a retrospective cohort of unselected octogenarian patients with NDMM treated with bortezomib dexamethasone (Vd). Seventy-four patients were treated with an initial doublet therapy (Vd regimen, 2−3 cycles, induction). A dose escalation with an adjunction of melphalan or cyclophosphamide was proposed for patients who had an insufficient response after induction and who could tolerate it. In responders, the treatment was continued until progression or a plateau response for 6 months (consolidation). The overall response rate was 73%. After a median follow-up of 31.4 months, median progression-free survival (PFS) and overall survival (OS) were 13.2 and 26.9 months, respectively. PFS and OS of patients with ECOG PS < 3 (25.4 and 54.9 months, respectively) were better in comparison to PFS and OS of patients with ECOG PS ≥ 3 (9.3 and 11.3 months, respectively). Thirteen patients (17.6%) died during induction. Twelve patients (16.2%) died during consolidation. In conclusion, a conservative therapeutic strategy based on Vd resulted in a good response rate. However, the survival remains poor in the population of patients with an ECOG PS ≥ 3, mainly because of early mortality not related to progressive disease.
RESUMEN
BACKGROUND: FOLFIRINOX is a pillar first-line regimen in the treatment of pancreatic cancer. Historically, biliary tract cancer (BTC) and pancreatic cancer have been treated similarly with gemcitabine alone or combined with a platinum compound. With growing evidence supporting the role of fluoropyrimidines in the treatment of BTC, we aimed at assessing the outcomes of patients (pts) with BTC on frontline FOLFIRINOX. METHODS: We retrospectively analyzed data of all our consecutive patients with locally advanced (LA) or metastatic (M) BTC who were registered to receive FOLFIRINOX as a first-line therapy between 12/2013 and 11/2017 at Paul Brousse university hospital. The main endpoints were Overall Survival (OS), Time-to-Progression (TTP), best Objective Response Rate (ORR), Disease Control rate (DCR), secondary macroscopically-complete resection (res) and incidence of severe (grade 3-4) toxicity (tox). RESULTS: There were 17 male (40%) and 25 female (60%) pts. aged 36 to 84 years (median: 67). They had PS of 0 (55%) or 1 (45%), and intrahepatic cholangiocarcinoma (CCA) (21 pts., 50%), gallbladder carcinoma (8 pts., 19%), perihilar CCA (7 pts., 17%), distal CCA (4 pts., 10%) and ampulloma (2 pts., 5%). BTC was LA or M in 10 (24%) and 32 pts. (76%) respectively. Biliary stent was placed in 14 pts. (33%). A median of 10 courses was given with median treatment duration of 6 months. There were no untoward toxicity issues, with no febrile neutropenia, emergency admission for toxicity or toxic death. We observed 12 partial responses (29%) and 19 disease stabilisations (45%). Six patients (14%) underwent secondary R0-R1 resection. Median TTP was 8 months [95%CL, 6-10] and median OS was 15 months [13-17]. Patients undergoing secondary resection displayed a 3-y disease-free rate of 83%. CONCLUSIONS: First-line FOLFIRINOX offers promising results in patients with LA and M-BTC. It deserves prospective evaluation to further improve outcomes for advanced BTC.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias del Sistema Biliar/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias del Sistema Biliar/mortalidad , Neoplasias del Sistema Biliar/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Francia/epidemiología , Humanos , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios RetrospectivosRESUMEN
FOLFIRINOX is one of the most effective reference regimens in the 1st line treatment of locally advanced (LA) and metastatic pancreatic cancer (mPC), despite its high toxicity. We evaluated our real-life experience with "patient-tailored intent to treat FOLFIRINOX" in patients with LA or mPC compared to other reports along with the pivotal phase III trial.We analyzed data from all consecutive patients with pancreatic ductal adenocarcinoma treated with dose-modified FOLFIRINOX in 2016 at Paul Brousse University Hospital. Irinotecan was administered whenever initial serum bilirubin was <1.5 × upper limit of normal. Oxaliplatin was stopped for severe sensory neuropathy. Initial dose reductions were made according to patient profile (eg, age, comorbidities) and later due to toxicity. The treatment was continued until surgery or disease progression. Endpoints were time to progression (TTP), overall survival (OS), objective response rate (ORR), and secondary complete resection (R0R1).Thirty-seven patients with unresectable LA or mPC received patient-tailored FOLFIRINOX as 1st line chemotherapy. There were 22 male (59%) and 15 female patients (41%) aged 44 to 81 years with LA (18 patients, 49%) and mPC (19 patients, 51%). They had World Health Organization-performance status of 0 (59%) or 1 (41%). A total of 384 cycles were administered. Median dose intensities (mg/m/w) were 28.9 for oxaliplatin, 56.8 for irinotecan, and 886.2 for 5-fluorouracil. Thirty-four patients were assessed for response; ORR and disease control rates were 47% and 85%, respectively. R0R1 rate was 30%. Median TTP and OS were 9.6 and 14.6 months. LA disease was associated with significantly longer TTP and OS (Pâ<â.001).FOLFIRINOX with patient-tailored dose adaptations seems to offer better results in patients with advanced PC. This approach in the neoadjuvant setting results in a macroscopic R0R1 in 61% of patients with initially unresectable disease. It deserves prospective evaluation to further improve outcomes in the management of advanced PC.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorouracilo/uso terapéutico , Leucovorina/uso terapéutico , Compuestos Organometálicos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán/administración & dosificación , Irinotecán/uso terapéutico , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organometálicos/administración & dosificación , Oxaliplatino/administración & dosificación , Oxaliplatino/uso terapéutico , Neoplasias Pancreáticas/mortalidad , Atención Dirigida al Paciente/métodos , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Elderly patients represent a heterogeneous population in which decisions on cancer treatment are often difficult. The present study aims to report a 2-year period of the activity of geriatric assessment consultations and the impact on treatment decisions. Since January 2007, we have systematically carried out geriatric consultations, using well-known international scales, for elderly patients in whom treatment decisions appear complex to oncologists. From January 2007 to November 2008, 161 patients (57 men, 104 women; median age 82.4 years, range 73-97) were seen at geriatric consultations. Most of the patients (134/161) were undergoing first-line treatment and cancer was metastatic in 86 patients (53%). Geriatric assessment found severe comorbidities (grade 3 or 4 in CIRS-G scale) in 75 patients, dependence for at least one activity of daily living (ADL) in 52 patients, cognitive impairment in 42 patients, malnutrition in 104 patients (65%) and depression in 39 patients. According to the oncologists' prior decisions, there were no changes in treatment decisions in only 29 patients. Cancer treatment was changed in 79 patients (49%), including delayed therapy in 5 patients, less intensive therapy in 29 patients and more intensive therapy in 45 patients. Patients for whom the final decision was delayed or who underwent less intensive therapy had significantly more frequent severe comorbidities (23/34, p<0.01) and dependence for at least one ADL (19/34, p<0.01). In this study, we have found that comprehensive geriatric evaluation did significantly influence treatment decisions in 82% of our older cancer patients.
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Atención Integral de Salud/métodos , Evaluación Geriátrica/métodos , Desnutrición/epidemiología , Neoplasias/terapia , Derivación y Consulta , Actividades Cotidianas , Factores de Edad , Anciano , Anciano de 80 o más Años , Causalidad , Comorbilidad , Depresión/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Neoplasias/epidemiología , Estudios RetrospectivosRESUMEN
In Europe, 60% of all cancers and 75% of all deaths from cancer occur in patients older than 65 years. The incidence of many cancers (prostate, colorectal, and hematological) either increases with age or remains high (breast and lungs). The two principal characteristics of cancer in the elderly are late diagnosis and comorbidity that requires specific geriatric assessment and cooperation between the oncologist and the geriatrician. Academic and pharmaceutical industry research must focus on the specificities of cancers in the elderly and of response to treatment according to functional abilities and comorbidity. Equal access to high quality medical care and procedures must be ensured, regardless of age; this is not currently the case everywhere.
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Geriatría/organización & administración , Oncología Médica/organización & administración , Neoplasias , Distribución por Edad , Anciano , Causas de Muerte , Comorbilidad , Diagnóstico Tardío , Industria Farmacéutica , Europa (Continente)/epidemiología , Femenino , Evaluación Geriátrica , Accesibilidad a los Servicios de Salud , Necesidades y Demandas de Servicios de Salud , Humanos , Incidencia , Masculino , Neoplasias/diagnóstico , Neoplasias/epidemiología , Neoplasias/terapia , Investigación , Distribución por Sexo , EspecializaciónRESUMEN
The epidermal growth factor receptor, a transmembrane receptor tyrosine kinase of the erbB family, is expressed in 15-30% of all breast cancers. Anti-epidermal growth factor receptor agent cetuximab is an IgG1 chimeric monoclonal antibody with a potent antitumor activity. Cetuximab competes with ligand binding to the epidermal growth factor receptor ectodomain, resulting in an efficient blockade of tumor-promoting downstream signaling pathways. Large clinical studies recently demonstrated cetuximab synergy with radiotherapy and chemotherapy agent irinotecan. Studies in human breast cancer xenografts showed cetuximab synergy with paclitaxel, a potent mitosis spindle-cell stabilizer. In this report, combined paclitaxel and cetuximab achieved a major reduction of the skin metastases of a heavily pretreated patient with epidermal growth factor receptor-positive, estrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor-2-negative (triple-negative) invasive ductal breast carcinoma. Treatment was well-tolerated overall and response was not correlated with the appearance of major cetuximab-induced acneiform rash.