RESUMO
In this case report, a novel N-acetylgalactosaminyltransferase 3 homozygous mutation (c.782 G>A; p.R261Q) associated with hyperphosphatemic familial tumoral calcinosis/hyperostosis-hyperphosphatemia syndrome is described. The patient had elbow, pelvis, and lower limb pain and a hard mass in the hip and olecranon regions. Increased levels of inorganic phosphorus (Pi) and C-reactive protein were observed. After treating the patient with conventional drugs, we tested denosumab, which reduced but did not normalize the Pi.
Assuntos
Calcinose , Denosumab , Hiperfosfatemia , N-Acetilgalactosaminiltransferases , Humanos , Hiperfosfatemia/tratamento farmacológico , Hiperfosfatemia/genética , Hiperfosfatemia/etiologia , Denosumab/uso terapêutico , Calcinose/genética , Calcinose/tratamento farmacológico , N-Acetilgalactosaminiltransferases/genética , Polipeptídeo N-Acetilgalactosaminiltransferase , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Mutação , Masculino , Hiperostose Cortical CongênitaRESUMO
AIMS: The combination of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (FOLFOX) is widely acknowledged as the standard regimen for second-line treatment in patients with advanced biliary tract cancer. Nanoliposomal irinotecan (nal-IRI) has demonstrated its activity in patients with advanced pancreatic cancer. Recent studies have investigated the activity of nal-IRI in combination with 5-FU/LV for biliary tract cancer. However, the results have been contradictory. We conducted a meta-analysis to assess survival outcomes and response rates in randomised trials investigating the activity of nal-IRI in previously treated biliary tract cancer patients. MATERIALS AND METHODS: We systematically collected potentially relevant findings from PubMed/Medline, the Cochrane library and EMBASE. Abstracts presented at major international oncological meetings were also reviewed. We extracted hazard ratios and 95% confidence intervals for progression-free survival and overall survival, as well as odds ratios and 95% confidence intervals for objective response rate. The outcomes of the accessible randomised studies evaluating the activity of nal-IRI plus 5-FU/LV were analysed. RESULTS: The combination therapy exhibited a statistically significant decrease in the risk of progression (hazard ratio 0.70; 95% confidence interval 0.50-0.97) when compared with 5-FU/LV alone. Additionally, the dual regimen yielded longer overall survival and a higher objective response rate. CONCLUSION: Our meta-analysis showed that nal-IRI plus 5-FU/LV had a superior activity in comparison with 5-FU/LV. Further investigations are required to elucidate the role of nal-IRI in this setting and to identify subgroups of patients who could derive the greatest benefit from its administration.
Assuntos
Neoplasias do Sistema Biliar , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Biliar/tratamento farmacológico , Fluoruracila/uso terapêutico , Irinotecano , Leucovorina/efeitos adversos , Lipossomos/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológicoRESUMO
BACKGROUND: Androgen-deprivation therapy (ADT) historically represented the milestone for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Recently, combining androgen receptor-targeted agents (ARTA) or docetaxel with ADT significantly improved clinical outcomes in this setting. The efficacy of the combined use of an ARTA with docetaxel and ADT (triplet), however, was unknown, and often conflicting data derived from subgroup analysis of randomized phase III trials. In order to better define the benefits and risks of the triplet in mHSPC, we carried out a systematic review and meta-analysis of available clinical trials. METHODS: A literature search with no data restriction using Medline/PubMed, the Cochrane Library, and American Society of Clinical Oncology/European Society for Medical Oncology (ASCO/ESMO) Meeting abstracts was carried out up to April 2022. The meta-analysis was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statements. Overall survival (OS) was the primary endpoint; progression-free survival (PFS) and safety were secondary endpoints. For OS and PFS, summary hazard ratios (HRs) were calculated; for safety, risk ratio (RR) was assessed. Random- or fixed-effects models were used, depending on studies heterogeneity. RESULTS: Five randomized clinical trials fulfilled the prespecified inclusion criteria. The triplet significantly improved OS (fixed-effect, HR = 0.74; P < 0.00001) and PFS (fixed-effect; HR = 0.50 for clinical PFS, HR = 0.49 for radiological PFS; P < 0.0001) compared with docetaxel plus ADT. We did not show heterogeneity between treatment efficacy and the disease burden, metachronous versus synchronous presentation, concomitant versus sequential strategy. Compared with docetaxel + ADT, the triplet did not increase the risk of adverse events (AEs) (RR = 1.00, P = 0.27 for any-grade AEs; RR = 1.13, P = 0.14 for severe AEs), except for severe hypertension (RR = 1.73, P = 0.001). CONCLUSIONS: Emerging evidence supports the combination of an ARTA plus docetaxel and ADT in mHSPC patients. Given the availability of several strategies in this setting, clinical characteristics and drug safety profile may help clinicians select the appropriate treatment for mHSPC patients who are more likely to benefit from treatment intensification.
Assuntos
Antineoplásicos , Neoplasias da Próstata , Masculino , Humanos , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Androgênios/uso terapêutico , Receptores Androgênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antineoplásicos/efeitos adversosRESUMO
Juvenile osteochondritis dissecans of the knee typically occurs in young athletes, and usually localizes on the medial femoral condyle. Bilateral localization is uncommon. Patellofemoral involvement is rare, mainly found in basketball and soccer players, and never related to patellofemoral congenital problems such as trochlear dysplasia. We report here the first case, to our knowledge, of bilateral juvenile osteochondritis dissecans with patellar localization in a young skier with patellofemoral maltracking and trochlear dysplasia.
Assuntos
Osteocondrite Dissecante , Patela , Adolescente , Campos Eletromagnéticos , Fêmur , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Osteocondrite Dissecante/diagnóstico por imagem , Osteocondrite Dissecante/terapia , Patela/diagnóstico por imagemRESUMO
AIM: To evaluate the accuracy of magnetic resonance imaging (MRI) and computed tomography (CT) in assessing the resection margins of primary malignant bone tumours. MATERIALS AND METHODS: Resected primary malignant bone tumour specimens removed from 46 patients (27 male; mean age: 48±22 years) were imaged using MRI (fat-saturated proton density-weighted and three-dimensional fat-suppressed T1-weighted gradient-recalled-echo) and CT immediately after surgery. A radiologist and an orthopaedist evaluated bone and soft-tissue margins of the specimens on both examinations. Histological evaluation was performed by a senior orthopaedic oncology pathologist. Margins were classified as R0 (safe margins), R1 (residuals between 0 and 1 mm), and R2 (macroscopic residuals). Cohen's k, chi-square, and McNemar's statistics were used. RESULTS: Having histology as the reference standard, reproducibility of the radiologist ranged from moderate (k=0.544) to substantial (k=0.741) for bone and soft-tissue margins on CT, respectively, while that of the orthopaedist ranged from fair (k=0.316) to moderate (k=0.548). When comparing R2 and R0+R1 scores, reproducibility of readers' evaluation of bone margins increased ranging from substantial (k=0.655) to perfect (k=1.000). Inter-reader agreement ranged from fair (k=0.308) to substantial (k=0.633). Accuracy of the radiologist and orthopaedist ranged from 76% to 83% and from 68% to 72%, respectively. When comparing R2 and R0+R1 scores, the accuracy of both readers ranged from 83% to 100%. There was no association between local recurrence and margin scores of histology, MRI, and CT (p≥0.058). CONCLUSIONS: MRI and CT may be useful for extemporaneous analysis of resection margins of primary malignant bone tumours, although wide accuracy variability between the different imaging methods was observed.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Imageamento por Ressonância Magnética/métodos , Margens de Excisão , Tomografia Computadorizada por Raios X/métodos , Neoplasias Ósseas/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico por imagem , Reprodutibilidade dos TestesRESUMO
Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer (PC). Most patients eventually progress to a condition known as castration-resistant prostate cancer (CRPC), characterized by lack of response to ADT. Although new androgen receptor signaling (ARS) inhibitors and chemotherapeutic agents have been introduced to overcome resistance to ADT, many patients progress because of primary or acquired resistance to these agents. This comprehensive review aims at exploring the mechanisms of resistance and progression of PC, with specific focus on alterations which lead to the activation of androgen receptor (AR)-independent pathways of survival. Our work integrates available clinical and preclinical data on agents which target these pathways, assessing their potential clinical implication in specific settings of patients. Given the rising interest of the scientific community in cancer immunotherapy strategies, further attention is dedicated to the role of immune evasion in PC.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/fisiologia , Humanos , Masculino , Transdução de Sinais/efeitos dos fármacosAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Receptor ErbB-2/biossíntese , Aminopiridinas/administração & dosagem , Benzimidazóis/administração & dosagem , Neoplasias da Mama/enzimologia , Quinases Ciclina-Dependentes/antagonistas & inibidores , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Feminino , Fulvestranto , Humanos , Letrozol , Nitrilas/administração & dosagem , Piperazinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Purinas/administração & dosagem , Piridinas/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Estrogênio/biossíntese , Medição de Risco , Triazóis/administração & dosagemRESUMO
OBJECTIVE: To compare chest X-ray with echocardiogram (ECHO) in the localization of an umbilical venous catheter (UVC) tip in very low birth weight infants (VLBW). Secondary objectives determined the association between techniques for tip placement by the vertebral body level on X-ray, as well as the length of the thoracic inferior vena cava-right atrial (TIVC-RA) junction by ECHO. STUDY DESIGN: Prospective, sequentially enrolled, masked, single regional perinatal center study. Shortly after birth, one or more anterior-posterior X-rays were ordered by the clinical team to verify that the UVC tip was fixed in the central right atrium (cRA) or at the TIVC-RA junction. An echocardiogram was performed as soon as possible after the last X-ray and UVC tip location was interpreted by a pediatric cardiologist. The pediatric radiologist and cardiologist were masked with regard to each other's reading. RESULTS: The newborns (nâ=â51) were 27 (±3) weeks by gestational age with birth weights of 1029 (±288) grams (mean±SD). The radiologist read 50 UVC tips (98%) in the cRA or TIVC-RA junction and 1 (2%) in the LA. The cardiologist read 22 (43%) in the cRA or TIVC-RA, 21 (41%) in the LA and 8 (16%) tips could not be located in the heart. When the UVC tip was interpreted by X-ray as located in the TIVC-RA junction 8/29 (28%) were in the LA by echocardiogram. There was no agreement between vertebral level and tip position in the TIVC-RA junction, RA or LA. The TIVC-RA junction measured 6±1âmm and correlated with birth weight râ=â0.54 (pâ<â0.001). CONCLUSION: In VLBW newborns, placement of the UVC tip into the cRA or TIVC-RA junction by X-ray does not avoid misplacement in the left atrium as demonstrated by echocardiography. For VLBW infants, it is suggested that echocardiography may be helpful in verifying that the original placement or migration of the UVC tip into the LA has not occurred.
Assuntos
Cateteres Venosos Centrais , Veias Umbilicais/diagnóstico por imagem , Cateterismo Venoso Central , Ecocardiografia , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Prospectivos , Radiografia Torácica , Cirurgia Assistida por Computador , Veia Cava Inferior/diagnóstico por imagemRESUMO
The present study was conducted to determine the potential effect of the dietary intake of fenugreek (Trigonella foenum graecum) seeds alone or in combination with Bacillus licheniformis, Lactobacillus plantarum or B. subtilis on gilthead seabream quality and antioxidant response after 2 and 3 weeks of experimental feeding. The results showed that the supplements did not affect the percentage of the fatty acid profiles of muscle, demonstrating that all the additives tested can be administrated without any negative effect on biochemical composition and quality of gilthead seabream. The quantification of thiobarbituric acid reactive substances in muscle demonstrated the significant beneficial effect of the experimental diets compared with the control one. Besides, an increase in superoxide dismutase and catalase in liver was recorded after 3 weeks of administration of experimental diets. Furthermore, real time qPCR revealed that dietary supplementation with FEBS significantly enhances the expression of scavenging enzymes, such as cat and gr genes in the liver after 3 weeks. The findings suggest that the administration of fenugreek supplement alone or combined with probiotic strains could be considered as a good source of natural antioxidants and as a functional aquafeed ingredient for gilthead seabream.
Assuntos
Suplementos Nutricionais , Imunidade Inata , Extratos Vegetais/metabolismo , Probióticos , Dourada/imunologia , Trigonella/metabolismo , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Bacillus licheniformis/química , Bacillus subtilis/química , Dieta/veterinária , Lactobacillus plantarum/química , Extratos Vegetais/administração & dosagem , Distribuição Aleatória , Dourada/metabolismoRESUMO
Consumption of tomato and tomato products is positively related to the reduction in cardiovascular disease and several types of cancer, thanks to the presence of natural compounds, such as antioxidants. Peels and seeds fractions of tomato, collected after industrial processing in Tunisian industries, were analysed for nutritional and antioxidants composition in perspective of its utilisation. Proximate composition, fatty acids profile, carotenoids, such as lycopene and beta-carotene, polyphenols contents, demonstrated the good potential of these residual products as a source of natural compounds, useful for food and nutraceuticals applications.
Assuntos
Produtos Biológicos/química , Solanum lycopersicum/química , Antioxidantes/análise , Compostos de Bifenilo/química , Carotenoides/análise , Carotenoides/farmacologia , Ácidos Graxos/análise , Manipulação de Alimentos , Indústria Alimentícia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Frutas/química , Licopeno , Picratos/química , Polifenóis/análise , Polifenóis/farmacologia , Sementes/química , TunísiaRESUMO
Carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections are an emerging cause of death after hematopoietic stem cell transplantation (HSCT). In allogeneic transplants, mortality rate may rise up to 60%. We retrospectively evaluated 540 patients receiving a transplant from an auto- or an allogeneic source between January 2011 and October 2015. After an Institutional increase in the prevalence of KPC-Kp bloodstream infections (BSI) in June 2012, from July 2012, 366 consecutive patients received the following preventive measures: (i) weekly rectal swabs for surveillance; (ii) contact precautions in carriers (iii) early-targeted therapy in neutropenic febrile carriers. Molecular typing identified KPC-Kp clone ST512 as the main clone responsible for colonization, BSI and outbreaks. After the introduction of these preventive measures, the cumulative incidence of KPC-Kp BSI (P=0.01) and septic shocks (P=0.01) at 1 year after HSCT was significantly reduced. KPC-Kp infection-mortality dropped from 62.5% (pre-intervention) to 16.6% (post-intervention). Day 100 transplant-related mortality and KPC-Kp infection-related mortality after allogeneic HSCT were reduced from 22% to 10% (P=0.001) and from 4% to 1% (P=0.04), respectively. None of the pre-HSCT carriers was excluded from transplant. These results suggest that active surveillance, contact precautions and early-targeted therapies, may efficiently control KPC-Kp spread and related mortality even after allogeneic HSCT.
Assuntos
Proteínas de Bactérias/biossíntese , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Infecções por Klebsiella , Klebsiella pneumoniae , Choque Séptico , beta-Lactamases/biossíntese , Adolescente , Adulto , Idoso , Aloenxertos , Autoenxertos , Feminino , Seguimentos , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Humanos , Infecções por Klebsiella/genética , Infecções por Klebsiella/mortalidade , Infecções por Klebsiella/terapia , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Klebsiella pneumoniae/patogenicidade , Masculino , Pessoa de Meia-Idade , Choque Séptico/genética , Choque Séptico/mortalidade , Choque Séptico/terapiaAssuntos
Transplante de Células-Tronco Hematopoéticas , Sirolimo/administração & dosagem , Condicionamento Pré-Transplante , Triazóis/administração & dosagem , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Doença de Hodgkin/terapia , Humanos , Leucemia Mieloide Aguda/terapia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Indução de Remissão , Risco , Transplante Homólogo , Resultado do Tratamento , Adulto JovemAssuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Monitorização Fisiológica/métodos , Proteínas Nucleares/genética , Adulto , Idoso , Aloenxertos , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/metabolismo , Nucleofosmina , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Hepatic focal nodular hyperplasia (FNH) is a nonmalignant condition rarely affecting children previously treated for cancer, especially those who received hematopoietic SCT (HSCT). Some aspects of its pathogenesis still remain unclear and a strong association with specific risk factors has not yet been identified. We report here a single institution's case series of 17 patients who underwent HSCT and were diagnosed with FNH, analyzing retrospectively their clinical features and the radiological appearance of their hepatic lesions. We aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) and to explore the role of transient elastography (FibroScan) to evaluate the degree of hepatic fibrosis in FNH patients. Our analysis showed an association of FNH with age at transplant ⩽12 years (hazard ratio (HR) 9.10); chronic GVHD (HR 2.99); hormone-replacement therapy (HR 4.02) and abdominal radiotherapy (HR 4.37). MRI proved to be a more accurate diagnostic tool compared with US. Nine out of 12 patients who underwent FibroScan showed hepatic fibrosis. Our study points out that FNH is an emerging complication of HSCT, which requires a lifelong surveillance to follow its course in cancer patients.
Assuntos
Hiperplasia Nodular Focal do Fígado/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Hiperplasia Nodular Focal do Fígado/patologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodosRESUMO
PURPOSE: Although achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some patients still relapse. The objectives of this study were to describe the types of events in this group of patients and to identify predictive factors for relapse. METHODS: Patients with large operable or locally advanced breast cancers (T4d tumours were excluded) were randomised to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel followed by three cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in the primary tumour and axillary lymph nodes at surgery. Two Cox regression analyses were performed to identify predictive factors of relapse: one for recurrence-free interval (RFI) and one for distant recurrence-free interval (DRFI). RESULTS: Out of 283 eligible patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6% (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors for RFI after pCR were identified. For DRFI, tumour size was the only predictor: Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR, 2.80 (95% CI, 0.62-12.64) p=0.0048. CONCLUSION: In this study, clinical tumour size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours having an increased risk for distant recurrence compared to T1-2 tumours.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carga Tumoral , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Progressão da Doença , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Metástase Neoplásica , Prognóstico , Recidiva , Indução de RemissãoRESUMO
We analyzed the outcome of 243 children with high-risk (HR) AML in first CR1 enrolled in the AIEOP-2002/01 protocol, who were given either allogeneic (ALLO; n=141) or autologous (AUTO; n=102) hematopoietic SCT (HSCT), depending on the availability of a HLA-compatible sibling. Infants, patients with AML-M7, or complex karyotype or those with FLT3-ITD, were eligible to be transplanted also from alternative donors. All patients received a myeloablative regimen combining busulfan, cyclophosphamide and melphalan; [corrected] AUTO-HSCT patients received BM cells in most cases, while in children given ALLO-HSCT stem cell source was BM in 96, peripheral blood in 19 and cord blood in 26. With a median follow-up of 57 months (range 12-130), the probability of disease-free survival (DFS) was 73% and 63% in patients given either ALLO- or AUTO-HSCT, respectively (P=NS). Although the cumulative incidence (CI) of relapse was lower in ALLO- than in AUTO-HSCT recipients (17% vs 28%, respectively; P=0.043), the CI of TRM was 7% in both groups. Patients transplanted with unrelated donor cord blood had a remarkable 92.3% 8-year DFS probability. Altogether, these data confirm that HSCT is a suitable option for preventing leukemia recurrence in HR children with CR1 AML.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/administração & dosagem , Condicionamento Pré-Transplante/métodos , Cariótipo Anormal , Adolescente , Aloenxertos , Autoenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Taxa de Sobrevida , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
BACKGROUND: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV: NCT00450892.