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2.
Ann Oncol ; 25(3): 623-628, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24399079

RESUMEN

BACKGROUND: A subgroup of T1N0M0 breast cancer (BC) carries a high potential of relapse, and thus may require adjuvant systemic therapy (AST). PATIENTS AND METHODS: Retrospective analysis of all patients with T1 BC, who underwent surgery from January 1999 to December 2009 at 13 French sites. AST was not standardized. RESULTS: Among 8100 women operated, 5423 had T1 tumors (708 T1a, 2208 T1b and 2508 T1c 11-15 mm). T1a differed significantly from T1b tumors with respect to several parameters (lower age, more frequent negative hormonal status and positive HER2 status, less frequent lymphovascular invasion), exhibiting a mix of favorable and poor prognosis factors. Overall survival was not different between T1a, b or c tumors but recurrence-free survival was significantly higher in T1b than in T1a tumors (P = 0.001). In multivariate analysis, tumor grade, hormone therapy and lymphovascular invasion were independent prognostic factors. CONCLUSION: Relatively poor outcome of patients with T1a tumors might be explained by a high frequency of risk factors in this subgroup (frequent negative hormone receptors and HER2 overexpression) and by a less frequent administration of AST (endocrine treatment and chemotherapy). Tumor size might not be the main determinant of prognosis in T1 BC.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Receptor ErbB-2/metabolismo , Adyuvantes Farmacéuticos/uso terapéutico , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Metástasis Linfática , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
3.
Ann Oncol ; 23(11): 2799-2805, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22771827

RESUMEN

BACKGROUND: Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways. A phase I trial demonstrated that the combination of gemcitabine and sorafenib was well tolerated and had activity in advanced pancreatic cancer (APC) patients. The BAYPAN study was a multicentric, placebo-controlled, double-blind, randomized phase III trial comparing gemcitabine/sorafenib and gemcitabine/placebo in the treatment of APC. PATIENTS AND METHODS: The patient eligibility criteria were locally advanced or metastatic pancreatic adenocarcinoma, no prior therapy for advanced disease and a performance status of zero to two. The primary end point was progression-free survival (PFS). The patients received gemcitabine 1000 mg/m(2) i.v., weekly seven times followed by 1 rest week, then weekly three times every 4 weeks plus sorafenib 200 mg or placebo, two tablets p.o., twice daily continuously. RESULTS: Between December 2006 and September 2009, 104 patients were enrolled on the study (52 pts in each arm) and 102 patients were treated. The median and the 6-month PFS were 5.7 months and 48% for gemcitabine/placebo and 3.8 months and 33% for gemcitabine/sorafenib (P = 0.902, stratified log-rank test), respectively. The median overall survivals were 9.2 and 8 months, respectively (P = 0.231, log-rank test). The overall response rates were similar (19 and 23%, respectively). CONCLUSION: The addition of sorafenib to gemcitabine does not improve PFS in APC patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Niacinamida/análogos & derivados , Neoplasias Pancreáticas/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Placebos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Ribonucleótido Reductasas/antagonistas & inhibidores , Sorafenib , Gemcitabina
4.
Clin Res Hepatol Gastroenterol ; 36(4): 371-7, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22361442

RESUMEN

UNLABELLED: Endoscopic resection (EMR) and radiofrequency ablation (RFA) form part of the treatment of Barrett's oesophagus (BO), dysplasia, superficial adenocarcinoma (OAC) associated with BO. PATIENTS AND METHODS: Between June 2008 and April 2011, 34 patients underwent treatment with RFA (HALO system(®)), in a tertiary centre. For the study, patients were divided into two groups. Group 1 (16 patients of average 60 years old; 14 men, two women) received EMR and RFA. Group 2 (18 patients averaging 59 years age; 14 men, four women) received RFA without EMR in the year preceding the RFA. RESULTS: In group 1, high grade dysplasia (HGD) was eradicated in 12 cases (92%), low grade dysplasia (LGD) in three cases (100%). Complete response occurred in nine cases (56%), partial response in 100% of cases. Mean follow-up was 15 months. In group 2, HGD was eradicated in one patient (100%), LGD in three patients (64%). A complete response was achieved in eight patients, partial response in four cases (77%). Mean follow-up was 10 months. The complication rate for groups 1 and 2 was of 18% and 10% respectively. No complication prevented completion of treatment or continued monitoring. Recurrence was evaluated to 5% in both groups. CONCLUSION: RFA associated with EMR is feasible, offering probably better results and a very important advantage: a more complete histology before follow-up. Our results show effective treatment of BO and associated dysplasia with a low rate of complication. Nevertheless, when new techniques of BO ablation are used, the need to obtain histology before treatment should not be forgotten.


Asunto(s)
Esófago de Barrett/cirugía , Ablación por Catéter , Esofagoscopía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/cirugía
5.
Bone Marrow Transplant ; 47(5): 639-45, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22307016

RESUMEN

We previously reported that reduced intensity conditioning (RIC) regimen with fludarabine, BU and 2.5 mg/kg of rabbit anti-thymocyte globulin (r-ATG) was effective but associated with a high rate of acute and chronic GVHD. Therefore, we increased the dose of r-ATG to 5 mg/kg. In this report, we analyzed 87 patients with AML or myelodysplastic syndrome (MDS) undergoing allo-SCT from an HLA-identical sibling donor from 2000 to 2010. RIC consisted of fludarabine, BU and r-ATG 2.5 mg/kg on 1 day (r-ATG1; n=53) or 2.5 mg/kg per day over 2 days (r-ATG2; n=22). Grade 2-4 acute GVHD incidence at day 100 was 30.2% and 8.8% in the r-ATG1 and r-ATG2 groups, respectively (P=0.038). Extensive chronic GVHD incidence was 60.4% and 12% in the r-ATG1 and r-ATG2 groups, respectively (P<0.001). The relapse incidences (RI) at 24 months were 18.9% and 28.5% in r-ATG1 and r-ATG2 groups, respectively (P=0.640). Overall and PFS were not different between the r-ATG1 and r-ATG2 groups. r-ATG dose at 5 mg/kg in the setting of RIC seems a good balance allowing GVHD prevention and antitumor effect with a remarkable reduction of GVHD incidence without an identical level of increased relapse rate.


Asunto(s)
Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/prevención & control , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Animales , Busulfano/uso terapéutico , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico , Persona de Mediana Edad , Síndromes Mielodisplásicos/complicaciones , Síndromes Mielodisplásicos/tratamiento farmacológico , Conejos , Recurrencia , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/efectos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapéutico
6.
Bone Marrow Transplant ; 47(4): 549-55, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21725375

RESUMEN

We report the first randomized study comparing early hospital discharge with standard hospital-based follow-up after high-dose chemotherapy (HDCT) and PBSCT. Patients aged 18-65 years, with an indication of PBSCT for non-leukemic malignant diseases were randomly assigned between two arms. Arm A consisted of early hospital discharge (HDCT during hospitalization, discharge at day 0, home stay with a caregiver, outpatient clinic follow-up). In arm B patients were followed up as inpatients. In total 131 patients were analyzed (66 in arm A and 65 in arm B). Patient characteristics and hematological reconstitution were comparable between the two groups. In arm A, 26 patients were actually discharged early. Patients in group A spent fewer days in hospital (11 vs 12 days, P=0.006). This strategy resulted in a 6% mean cost reduction per patient when compared with the conventional hospital-based group. The early discharge approach within the French health system, while safe and feasible, is highly dependent on social criteria (caregiver availability and home to hospital distance). It is almost always associated with conventional hospital readmission during the aplasia phase, and limits cost savings when considering the whole population of patients benefiting from HDCT in routine clinical practice.


Asunto(s)
Hospitalización/economía , Neoplasias/economía , Trasplante de Células Madre/economía , Adulto , Costos y Análisis de Costo , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/terapia , Alta del Paciente/economía , Trasplante de Células Madre/métodos , Factores de Tiempo , Trasplante Autólogo
7.
Acta Anaesthesiol Scand ; 56(2): 178-89, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22150473

RESUMEN

BACKGROUND: The short-term survival of critically ill patients with cancer has improved over time. Studies providing long-term outcome for these patients are scarce. METHODS: We prospectively analyzed outcomes and rates of successful discharge of 111 consecutive critically ill cancer patients admitted to intensive care unit (ICU) in 2008 and identified factors influencing these results. RESULTS: ICU mortality was 32% and hospital mortality was 41%. None of the characteristics of the malignancy nor age or neutropenia were significantly different between survivors and others. Two variables were independently associated with ICU mortality: high Logistic Organ Dysfunction score on day 7 and a diagnosis of viral infection and/or reactivation. The 1-year mortality rate for ICU survivors was 58% and was significantly lower in patients with a diagnosis of acute leukemia or multiple myeloma. CONCLUSION: Organ failure scores on day 7 can predict outcome for cancer patients in the ICU. Viral infection and reactivation appear to worsen the prognosis. One-year mortality rate is high and depends on the malignancy.


Asunto(s)
Cuidados Críticos , Enfermedad Crítica/mortalidad , Neoplasias/mortalidad , Neoplasias/terapia , APACHE , Anciano , Comorbilidad , Femenino , Mortalidad Hospitalaria , Humanos , Infecciones/microbiología , Infecciones/mortalidad , Infecciones/virología , Unidades de Cuidados Intensivos , Tiempo de Internación , Escala de Lod , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/mortalidad , Neoplasias/complicaciones , Alta del Paciente , Pronóstico , Estudios Prospectivos , Insuficiencia Respiratoria/etiología , Análisis de Supervivencia , Sobrevivientes , Resultado del Tratamiento
8.
Cancer Radiother ; 15(4): 279-86, 2011 Jul.
Artículo en Francés | MEDLINE | ID: mdl-21515083

RESUMEN

PURPOSE: Neoadjuvant chemoradiation followed by surgery is the standard of care for locally advanced rectal cancer. The aim of this study was to correlate tumour response to survival and to identify predictive factors for tumour response after chemoradiation. PATIENTS AND METHODS: From 1998 to 2008, 168 patients with histologically-proven locally advanced adenocarcinoma treated by preoperative chemoradiation before total mesorectal excision were retrospectively studied. They received a radiation dose of 45 Gy with a concomitant 5-fluoro-uracil-based chemotherapy. Analysis of tumour response was based on the lowering of T stage between pre-treatment endorectal ultrasound and pathologic specimens. Overall and progression-free survival was correlated with tumour response. Tumour response was analysed with predictive factors. RESULTS: The median follow-up was 34 months. Five-year disease-free survival and overall survival were respectively of 44.4% and 74.5% in the whole population, 83.4% and 83.4% in patients with pathological complete response, 38.6% and 71.9% in patients with tumour downstaging, 29.1% and 58.9% in patients with absence of response. A pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was significantly associated with tumour downstaging and significantly independently associated with pathologic complete tumour response (P = 0.019). CONCLUSION: Downstaging and complete response after chemoradiation improved progression-free survival and overall survival of locally advanced rectal adenocarcinoma. In multivariate analysis, a pre-treatment concentration of carcinoembryonnic antigen below 5 ng/mL was associated with complete tumour response, hence with tumour downstaging.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Pronóstico , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
9.
Bone Marrow Transplant ; 46(7): 1000-5, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20921945

RESUMEN

In this retrospective study, 63 patients >60 years with hematological malignancies and treated with allo-SCT and with reduced-intensity conditioning (RIC) were reviewed. A total of 51% of patients suffered from AML or myelodysplastic syndromes. Disease status before transplantation was CR or PR 71 with 29% transplanted with active disease. Patients were classified according to three published prognostic indexes: (1) hematopoietic cell transplantation comorbidity index (HCT-CI); (2) European BMT (EBMT) score; and (3) Pretransplantation Assessment of Mortality (PAM) score. The 100-day and 1-year treatment-related mortality (TRM) were 6 and 22%, respectively, for the entire group. The 2-year OS and PFS were 60 and 58%, respectively. The incidence of grade II-IV acute GVHD (aGVHD) and extensive chronic GVHD was 46 and 48%, respectively. In a univariate analysis, neither the HCT-CI nor the EBMT score, nor the PAM score were predictive of TRM and OS. Only the occurrence of aGVHD affected the TRM and OS. ALLO-RIC is feasible in elderly patients. Even if those prognostic scores were not adapted to elderly patients, they did not predict for TRM and OS. aGVHD is the main cause of TRM and more efforts should be made to reduce its incidence without sacrificing graft vs tumor effect.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Anciano , Trasplante de Células Madre Hematopoyéticas/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Acondicionamiento Pretrasplante/estadística & datos numéricos , Trasplante Homólogo/métodos , Trasplante Homólogo/estadística & datos numéricos , Resultado del Tratamiento
10.
Crit Rev Oncol Hematol ; 76(1): 71-8, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20356760

RESUMEN

BACKGROUND: Elderly metastatic cancer patients typically have short life expectancy and frequently suboptimal treatment. Goals of therapy should include preservation of functional status as well as clinical response. For elderly patients, oral chemotherapy could be a valuable strategy, avoiding the constraints and risks of intravenous drugs. METHODS: This study assessed effect of an all-oral combination of capecitabine and vinorelbine on functional status (measured by basic Activities of Daily Living [ADL]), toxicity, efficacy and compliance in patients ≥70 years with advanced breast, prostate or lung cancer. RESULTS: Eighty patients were enrolled. After three cycles, 81.8% of patients had stabilised or improved ADL, and 8.6% and 42.9% had a response or stabilised disease. Compliance was excellent (68.8%). The most common grade 3-4 toxicities were haematological (17.9%) and gastrointestinal (7.7%). CONCLUSION: In elderly cancer patients, an all-oral combination of capecitabine and vinorelbine maintains functional status, is well tolerated, and provides good disease control.


Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Fluorouracilo/análogos & derivados , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Vinblastina/análogos & derivados , Administración Oral , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/uso terapéutico , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Masculino , Análisis de Supervivencia , Resultado del Tratamiento , Vinblastina/administración & dosificación , Vinblastina/efectos adversos , Vinblastina/uso terapéutico , Vinorelbina
11.
Eur J Cancer Care (Engl) ; 19(6): 827-32, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19708949

RESUMEN

Removal of residual masses after chemotherapy in non-seminomatous germ cell tumours (NSGCTs) remains the standard of care. We evaluated in a retrospective and monocentric study potential prognostic factors. Fifty-one patients underwent surgery after chemotherapy for NSGCT. We estimated event-free survival with Kaplan-Meier method and used Cox proportional hazards regression analysis to assess the prognostic significance of risk factors. Histology of residual masses revealed fibrosis in 25 (49%), mature teratoma in 18 (35%) and viable germ cells in 8 (16%). Alpha-fetoprotein mean level at diagnosis was higher in patients with residual masses showing mature teratoma and/or viable malignant cells (P = 0.036). In multivariate analysis, poor prognosis group according to International Germ Cell Cancer Collaborative Group was associated with worse outcome compared with good and intermediate prognosis groups (hazard ratio for events = 26.4; 95% confidence interval 2.46-283.9; P = 0.006) and primary testicular NSGCT was associated with better event-free survival than extragonadal NSGCTs (hazard ratio for events = 0.04; 95% confidence interval 0.004-0.48; P = 0.01). Resection of residual masses after chemotherapy in NSGCT results in favourable long-term survival in most patients. Our results compared favourably with those reported from higher volume centres.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias Testiculares/cirugía , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neoplasia Residual , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/patología , Evaluación de Resultado en la Atención de Salud , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias Testiculares/patología , Adulto Joven
12.
Eur J Surg Oncol ; 35(7): 690-5, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19046847

RESUMEN

PURPOSE: Predictive factors of non-sentinel lymph node (NSN) involvement at axillary lymph node dissection (ALND) have been studied in the case of sentinel node (SN) involvement, with validation of a nomogram. This nomogram is not accurate for SN micrometastasis. The purpose of our study was to determine a nomogram for predicting the likelihood of NSN involvement in breast cancer patients with a SN micrometastasis. METHODS: We collated 909 observations of SN micrometastases with additional ALND. Characteristics of the patients, tumours and SN were analysed. RESULTS: Involvement of SN was diagnosed 490 times (53.9%) with standard staining (HES) and 419 times solely on immunohistochemical analysis (IHC) (46.1%). NSN invasion was observed in 114 patients (12.5%), whereas 62.3% (71) had only one NSN involved and 37.7% (43) two or more NSN involved. In multivariate analysis, significant predictive factors were: tumour size (pT stage < or = 10 mm or >11 and < or = 20 or >20 mm [odds ratio (OR) 2.1 and 3.43], micrometastases detected by HES or IHC [OR 1.64], presence or absence of lymphovascular invasion (LVI) [OR 1.76], tumour histological type mixed or not [OR 2.64]. The rate and probability of NSN involvement with the model are given for 24 groups, with a representation by a nomogram. CONCLUSION: One group, corresponding to 10.1% of the patients, was associated with a risk of NSN involvement of less than 5%, and five groups, corresponding to 29.8% of the patients, were associated with a risk < or = 10%. Omission of ALND could be proposed with minimal risk for a low probability of NSN involvement.


Asunto(s)
Neoplasias de la Mama/patología , Ganglios Linfáticos/patología , Nomogramas , Biopsia del Ganglio Linfático Centinela , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Modelos Biológicos , Valor Predictivo de las Pruebas , Estudios Retrospectivos
13.
Ann Oncol ; 19(9): 1624-8, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18467313

RESUMEN

BACKGROUND: Erlotinib is an orally active small-molecule tyrosine kinase inhibitor targeted against human epidermal growth factor receptor 1/epidermal growth factor receptor (ErbB1), known to be overexpressed in a variety of cancers, including prostate cancer. PATIENTS AND METHODS: This was a phase II monocentric study of 30 patients with advanced or metastatic prostate cancer, 29 had castration-resistant prostate cancer and 23 had received prior chemotherapy. Patients received erlotinib: 150 mg/day, increased to 200 mg at week 4, and continued until progression or unacceptable toxicity. Efficacy was defined as a decrease or stabilization of prostate-specific antigen (PSA) without clinical progression. Clinical benefit was evaluated by Karnofsky performance status and pain intensity, and response was an improvement in one of these parameters without worsening in the other. RESULTS: Median age was 69 years (range 51-77 years), and median PSA 102 ng/ml (range 3-1213 ng/ml). Dose escalation to 200 mg was possible in 16 (55%) patients. Moderate toxicity was observed. No patient had a decrease in PSA, 14% had stabilization, less than the >or=20% expected. PSA-doubling time, evaluated before and after erlotinib, was increased for 10 patients (P = 0.0058). Clinical benefit was achieved in 40% of patients. CONCLUSION: Erlotinib demonstrated an improvement in clinical benefit. Future directions should include evaluating its use in less advanced prostate cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Quinazolinas/administración & dosificación , Adenocarcinoma/mortalidad , Administración Oral , Anciano , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Clorhidrato de Erlotinib , Humanos , Estimación de Kaplan-Meier , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Probabilidad , Pronóstico , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Inhibidores de Proteínas Quinasas/efectos adversos , Quinazolinas/efectos adversos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
14.
Eur J Surg Oncol ; 34(5): 569-75, 2008 May.
Artículo en Inglés | MEDLINE | ID: mdl-17531428

RESUMEN

OBJECTIVES: To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy. METHODS: One hundred and forty-four patients with biopsy-proven stage IB-IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status. RESULTS: Tumour FIGO stages were IB-II in 91 cases and III-IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB-II and III-IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1-67.5] and 65% [95% CI: 56.2-75]. OS was significantly affected by the type of surgery (p<2.10(-16)), the presence of tumoural residue (p=0.002) and the pelvic lymphatic status (p<0.001). DFS was affected by the pelvic (p=0.02) and para-aortic lymphatic status (p=0.009). No significant difference was observed between OS and DFS in stage IB-II and III-IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p=0.022). CONCLUSION: Survival rates were equivalent between patients with IB-II and III-IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.


Asunto(s)
Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Radioterapia , Análisis de Supervivencia , Neoplasias del Cuello Uterino/patología
15.
Bone Marrow Transplant ; 39(8): 453-60, 2007 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17334384

RESUMEN

Cord blood (CB) units are increasingly used for allogeneic transplantation. Cell dose, a major factor for CB selection, is evaluated before freezing by each CB bank, using various techniques. This may introduce variability and affect the prediction of cell recovery after thawing, or haematopoietic reconstitution. Forty-two children were transplanted at the same institution with unrelated CB units. All units were thawed and evaluated at the same cell therapy facility, using standard procedures. We investigated: (i) factors that affect cell loss after thawing, and (ii) the importance of CD34(+) cell doses. Prefreeze and post-thaw CD34(+) cell doses were statistically correlated, thus suggesting that variability in numeration techniques used by different CB banks does not compromise the biological and clinical value of these figures. CD34(+) cell recovery appeared to be correlated with the absolute number of CD34(+) cells per frozen bag. Infused CD34(+) is the cell dose that better correlates with platelet reconstitution delay; in addition, when using a quartile comparison, haematopoietic recovery appeared to be related with prefreeze and post-thaw CD34(+) cell doses. We conclude that enumeration of CD34(+) cells in CB units is of biological significance, and may help select CB units and identify patients at risk of delayed recovery.


Asunto(s)
Antígenos CD34/sangre , Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Neoplasias/terapia , Antígenos CD/sangre , Técnicas de Cultivo de Célula/normas , Niño , Trasplante de Células Madre de Sangre del Cordón Umbilical/normas , Sangre Fetal , Trasplante de Células Madre Hematopoyéticas/normas , Humanos , Inmunosupresores/uso terapéutico , Cinética , Recuento de Leucocitos , Recuento de Plaquetas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Irradiación Corporal Total
16.
Oncogene ; 26(2): 298-307, 2007 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-16819513

RESUMEN

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.


Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Neoplasias de la Mama/genética , Rotura Cromosómica , Cinesinas/genética , Miosinas/genética , Proteínas de Neoplasias/genética , Ubiquitina-Proteína Ligasas/genética , Ácido Anhídrido Hidrolasas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/genética , Carcinoma Lobular/metabolismo , Sitios Frágiles del Cromosoma , Cromosomas Humanos Par 6/genética , Femenino , Técnica del Anticuerpo Fluorescente , Genes Supresores de Tumor , Humanos , Técnicas para Inmunoenzimas , Hibridación Fluorescente in Situ , Cinesinas/metabolismo , MicroARNs , Persona de Mediana Edad , Miosinas/metabolismo , Invasividad Neoplásica/patología , Proteínas de Neoplasias/metabolismo , Pronóstico , Interferencia de ARN , Tasa de Supervivencia , Análisis de Matrices Tisulares , Ubiquitina-Proteína Ligasas/metabolismo
17.
Bone Marrow Transplant ; 38(3): 217-22, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16770316

RESUMEN

The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Células B/terapia , Linfoma de Células B Grandes Difuso/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Adulto , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales de Origen Murino , Antígenos CD20/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cisplatino/administración & dosificación , Terapia Combinada , Ciclofosfamida/administración & dosificación , Epirrubicina/administración & dosificación , Etopósido/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Pronóstico , Rituximab , Análisis de Supervivencia , Trasplante Autólogo , Vincristina/administración & dosificación
18.
Oncogene ; 25(7): 981-9, 2006 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-16186794

RESUMEN

A total of 30-50% of early breast cancer (EBC) patients considered as high risk using standard prognostic factors develop metastatic recurrence despite standard adjuvant systemic treatment. A means to better predict clinical outcome is needed to optimize and individualize therapeutic decisions. To identify a protein signature correlating with metastatic relapse, we performed surface-enhanced laser desorption/ionization-time of flight mass spectrometry profiling of early postoperative serum from 81 high-risk EBC patients. Denatured and fractionated serum samples were incubated with IMAC30 and CM10 ProteinChip arrays. Several protein peaks were differentially expressed according to clinical outcome. By combining partial least squares and logistic regression methods, we built a multiprotein model that correctly predicted outcome in 83% of patients. The 5-year metastasis-free survival in 'good prognosis' and 'poor prognosis' patients as defined using the multiprotein index were strikingly different (83 and 22%, respectively; P<0.0001, log-rank test). In a multivariate Cox regression including conventional pathological factors and multiprotein index, the latter retained the strongest independent prognostic significance for metastatic relapse. Major components of the multiprotein index included haptoglobin, C3a complement fraction, transferrin, apolipoprotein C1 and apolipoprotein A1. Therefore, postoperative serum protein pattern may have an important prognostic value in high-risk EBC.


Asunto(s)
Proteínas Sanguíneas/análisis , Neoplasias de la Mama/tratamiento farmacológico , Proteómica , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Periodo Posoperatorio , Pronóstico , Análisis por Matrices de Proteínas , Recurrencia
19.
Bone Marrow Transplant ; 36(10): 901-6, 2005 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16151421

RESUMEN

The use of recombinant human erythropoietin (rHuEPO) has been controversial after myeloablative allogeneic Stem cell transplantation (allo-SCT). Reduced intensity conditioning regimens (RIC) offer a novel approach that might translate into a different profile of erythropoietic recovery. We treated 20 consecutive patients with rHuEPO early after matched sibling RIC allo-SCT. Conditioning included fludarabine, busulfan and antithymocyte globulin. EPO treatment was analyzed in terms of toxicity, impact on the frequency of Red blood cell transfusions (RBCT) and kinetics of Hemoglobin recovery within the 60 days post-allo-SCT. Results were compared with 27 matched patients who did not receive rHuEPO. In the first 2 months after allo-SCT all patients receiving rHuEPO (100%) achieved an Hb level > 11 g/dl at a median of 30 (15-35) days post-allo-SCT, as compared to only 63% of the patients not receiving rHuEPO (P = 0.007) at a median of 35 (20-55) days (P = 0.03). A total of 70% (95% CI, 50-90) of rHuEPO patients maintained an Hb over 11 g/dl in the second month as compared to only 19% (95% CI, 4-34) in the other group (P = 0.0004). For patients receiving RBCT, the use of rHuEPO was associated with a trend towards reduced RBCT requirements. This pilot study suggests a potential benefit of early administration of rHuEPO after RIC allo-SCT on early erythropoietic recovery.


Asunto(s)
Eritropoyetina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas/métodos , Hemoglobinas/efectos de los fármacos , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Eritropoyesis/efectos de los fármacos , Eritropoyetina/toxicidad , Femenino , Neoplasias Hematológicas/terapia , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Proyectos Piloto , Proteínas Recombinantes , Trasplante Homólogo
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