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1.
J Oncol Pharm Pract ; 27(4): 842-846, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32660379

RESUMEN

PURPOSE: A retrospective monocentric comparison of progression-free survival, overall survival, clinical benefit and tolerability between elderly (age>70) and non-elderly (age ≤ 70) patients receiving bevacizumab for recurrent glioblastoma. METHODS: We analyzed 47 patients with recurrent glioblastoma receiving bevacizumab (10 mg/kg every 14 days) between January 2011 and January 2014. Bevacizumab was introduced for all patients at recurrence after a first-line treatment by temozolomide. RESULTS: Nineteen patients were classified as elderly and 28 patients as non-elderly. No statistically significant difference was detected in the groups in terms of progression-free survival (3.8 vs. 4.1 months, p > 0.05) and overall survival at relapse (5.5 vs. 6.5 months, p > 0.05). A significant (p = 0.01) improvement of Karnofsky Performance Status Scale was observed in non-elderly patients. CONCLUSIONS: Despite the small number of patients in this retrospective study, the efficacy and safety of bevacizumab in recurrent glioblastoma appear similar in elderly and non-elderly patients. However, clinical benefit seemed to be less evident in younger patients. A prospective multicentric study integrating geriatric assessment tools and quality of life metrics would be interesting in this patient population.


Asunto(s)
Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adulto , Factores de Edad , Anciano , Antineoplásicos Alquilantes/uso terapéutico , Femenino , Evaluación Geriátrica , Humanos , Estado de Ejecución de Karnofsky , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Calidad de Vida , Estudios Retrospectivos , Análisis de Supervivencia , Temozolomida/uso terapéutico
2.
Cancer Invest ; 37(10): 531-534, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31619066

RESUMEN

Background: Head and neck cancer is particular due to its infiltrative nature and lymphatic extension, with multidisciplinary treatment. Immunotherapy may be a brand-new therapeutic approach.Case Presentation: We report a case of patient with advanced head and neck cancer resistant to cytotoxic treatment, with astonishing response to antibodies anti Programmed Death 1 (PD1).Conclusion: Further studies are needed in order to obtained predictive index of immunotherapy responding, aiming to select appropriately patients for this treatment.


Asunto(s)
Neoplasias Orofaríngeas/inmunología , Neoplasias Orofaríngeas/terapia , Antineoplásicos/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/inmunología , Humanos , Inmunoterapia/métodos , Masculino , Persona de Mediana Edad , Neoplasias Orofaríngeas/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo
3.
BMC Cancer ; 18(1): 1127, 2018 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-30445935

RESUMEN

BACKGROUND: The ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT). METHODS: Patients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. RESULTS: Responses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk ('over prophylaxis'). Nearly half of patients' CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed. CONCLUSIONS: Use of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians' decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%.


Asunto(s)
Biosimilares Farmacéuticos/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/prevención & control , Filgrastim/uso terapéutico , Neoplasias/tratamiento farmacológico , Anciano , Neutropenia Febril Inducida por Quimioterapia/metabolismo , Estudios de Cohortes , Femenino , Francia , Factor Estimulante de Colonias de Granulocitos/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/metabolismo , Estudios Prospectivos , Factores de Riesgo
4.
Front Oncol ; 14: 1319792, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706606

RESUMEN

Choroidal melanoma (CM) is the most common malignant ocular tumor in adults. The current treatment of metastatic CM is limited by the intrinsic resistance of CM to conventional systemic therapies. Immunotherapy alone or in association with cytotoxic treatment became a realist option treatment. Advancements in molecular biology have resulted in the identification of a number of promising prognostic and therapeutic targets. Herein, we report a rare case of 36-year-old patient with metastatic CM who presented a good long response to treatment with double immunotherapy reaching 3 years of overall survival, which has never been described in the literature.

5.
Nat Commun ; 15(1): 1985, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38443333

RESUMEN

Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5-5.9) and 4.9 months (95%CI 2.9-7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ováricas , Femenino , Humanos , Anticuerpos Monoclonales , Bevacizumab/uso terapéutico , Carcinoma Epitelial de Ovario , Enfermedad Crónica , Neoplasias Ováricas/tratamiento farmacológico , Ftalazinas , Piperazinas , Platino (Metal) , Recurrencia , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
6.
Cancers (Basel) ; 14(2)2022 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-35053621

RESUMEN

BACKGROUND: Hemostatic complications, ranging from thromboembolism to bleeding, are a significant source of morbidity and mortality in cancer patients. The tumor coagulome represents the multiple genes and proteins that locally contribute to the equilibrium between coagulation and fibrinolysis. We aimed to study the coagulome of Oral Squamous Cell Carcinoma (OSCC) and examine its link to the tumor microenvironment (TME). METHODS: We used data from bulk tumor DNA/RNA-seq (The Cancer Genome Atlas), single-cell RNA-seq data and OSCC cells in culture. RESULTS: Among all tumor types, OSCC was identified as the tumor with the highest mRNA expression levels of F3 (Tissue Factor, TF) and PLAU (urokinase type-plasminogen activator, uPA). Great inter- and intra-tumor heterogeneity were observed. Single-cell analyses showed the coexistence of subpopulations of pro-coagulant and pro-fibrinolytic cancer cells within individual tumors. Interestingly, OSCC with high F3 expressed higher levels of the key immune checkpoint molecules CD274/PD-L1, PDCD1LG2/PD-L2 and CD80, especially in tumor dendritic cells. In vitro studies confirmed the particularity of the OSCC coagulome and suggested that thrombin exerts indirect effects on OSCC cells. CONCLUSIONS: OSCC presents a specific coagulome. Further studies examining a possible negative modulation of the tumor's adaptive immune response by the coagulation process are warranted.

7.
Cancers (Basel) ; 13(18)2021 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-34572788

RESUMEN

PURPOSE: There is a clinical need to better non-invasively characterize the tumor microenvironment in order to reveal evidence of early tumor response to therapy and to better understand therapeutic response. The goals of this work are first to compare the sensitivity to modifications occurring during tumor growth for measurements of tumor volume, immunohistochemistry parameters, and emerging ultrasound parameters (Shear Wave Elastography (SWE) and dynamic Contrast-Enhanced Ultrasound (CEUS)), and secondly, to study the link between the different parameters. METHODS: Five different groups of 9 to 10 BALB/c female mice with subcutaneous CT26 tumors were imaged using B-mode morphological imaging, SWE, and CEUS at different dates. Whole-slice immunohistological data stained for the nuclei, T lymphocytes, apoptosis, and vascular endothelium from these tumors were analyzed. RESULTS: Tumor volume and three CEUS parameters (Time to Peak, Wash-In Rate, and Wash-Out Rate) significantly changed over time. The immunohistological parameters, CEUS parameters, and SWE parameters showed intracorrelation. Four immunohistological parameters (the number of T lymphocytes per mm2 and its standard deviation, the percentage area of apoptosis, and the colocalization of apoptosis and vascular endothelium) were correlated with the CEUS parameters (Time to Peak, Wash-In Rate, Wash-Out Rate, and Mean Transit Time). The SWE parameters were not correlated with the CEUS parameters nor with the immunohistological parameters. CONCLUSIONS: US imaging can provide additional information on tumoral changes. This could help to better explore the effect of therapies on tumor evolution, by studying the evolution of the parameters over time and by studying their correlations.

8.
Cancers (Basel) ; 13(15)2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-34359788

RESUMEN

BACKGROUND: The identification of activating mutations in specific genes led to the development of targeted therapies for NSCLC. TKI directed against EGFR-mutations were the first to prove their major efficacy. Medical associations recommend their use as first and second-line metastatic treatments in EGFR-mutated patients. Our objective was to analyze the survival of EGFR-mutated patients treated beyond the second line of treatment. METHODS: We performed a longitudinal, retrospective and analytical study at APHP (Assistance Publique Hopitaux de Paris) Saint Louis, Paris, France, from 1 January 2010 to 31 December 2020 (11 years), on EGFR-mutated patients with metastatic NSCLC which received TKI or chemotherapy (CT) in third-line. RESULTS: Out of about 107 EGFR-mutated patients, 31 patients who benefited from TKI or CT in the third line of treatment were retained for this study. The mean age was 60.03 ± 11.93 years and the sex ratio male/female was 0.24. Mutations of exon 19, 21 and 20 were found in 21 (67.7%), 7 (22.6%) and 7 (22.6%) patients, respectively. Third-line treatment was CT for 16 patients (51.6%) and TKI for the 15 remaining patients (48.4%). Osimertinib was the most used TKI in third-line (n = 10/15; 66.67%). The median duration of third-line treatment was 5.37 months (range 0.53-37.6) and the median follow-up duration was 40.83 months (range 11.33-88.57). There was a significant difference in PFS between patients treated with TKI and CT in third-line (p = 0.028). For patients treated with CT in second-line, there was a significant difference of PFS (p < 0.001) and OS (p = 0.014) in favor of the use of TKI in third-line. CONCLUSIONS: For patients receiving CT in second-line, TKI appears to be a better alternative in third-line compared to CT. Osimertinib may be used in third line treatment if not used before.

9.
Transl Oncol ; 14(8): 101110, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33951601

RESUMEN

OBJECTIVES: The immune checkpoint molecule PD-L1 (CD274) is a crucial regulator of the tumor immune response. Its expression has been reported in the therapeutic context in Head and Neck Squamous Cell Carcinoma (HNSCC), but it remains unclear how therapeutically approved molecules regulate PD-L1 expression in HNSCC cells. MATERIALS AND METHODS: Three HNSCC cell lines (BICR6, PE/CA-PJ34 and PE/CA-PJ41) were used to analyze PD-L1 expression by immunoblotting, immunofluorescence and QPCR. Freely-available single cell RNAseq data from HNSCC were also used. RESULTS: 5-Fluorouracil (5-FU) increased the expression of PD-L1 with high efficacy in HNSCC cells. Single cell RNAseq data suggested the specificity of the regulation of PD-L1 in this context. The effect of 5-FU on PD-L1 expression was related to its genotoxic effect and was prevented by extracellular application of thymidine or using a chemical inhibitor of the DNA damage Response kinases ATM/ATR. We found that the effect of 5-FU was additive or synergistic with IFN-γ, the canonical inducer of PD-L1 in epithelial cells. QPCR analysis confirmed this finding and identified JAK-dependent transcriptional activation of PD-L1/CD274 as the underlying mechanism. The induction of PD-L1 by 5-FU was partially prevented by Epidermal Growth Factor Receptor (EGFR) inhibition with cetuximab. CONCLUSION: Our study highlights the specific DNA Damage Response- and JAK- dependent induction of PD-L1 by 5-FU in HNSCC cells. This induction is regulated by the cytokine context and is potentially therapeutically actionable.

10.
Mol Clin Oncol ; 13(3): 2, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32754316

RESUMEN

Colorectal cancer (CRC) is one of the most common malignancies worldwide, with common sites of metastases including abdominal lymph nodes, the liver and lungs. Bone metastases are known to be relatively rare sites of metastasis. The present study reported a patient with advanced colorectal cancer and metastatic colorectal cancer (mCRC) with atypical metastases presentation. Bone mCRCs were not frequent and presented a poor prognosis in the present case. It was concluded that further studies are required to clarify the pathogenesis of bone metastases, to improve the management and treatment of patients.

11.
Technol Cancer Res Treat ; 19: 1533033819886896, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32065066

RESUMEN

BACKGROUND: Association of drugs acting against different antiangiogenic mechanisms may increase therapeutic effect and reduce resistance. Noninvasive monitoring of changes in the antiangiogenic response of individual tumors could guide selection and administration of drug combinations. Noninvasive detection of early therapeutic response during dual, vertical targeting of the vascular endothelial growth factor pathway was investigated in an ectopic subcutaneous xenograft model for human pancreatic tumor. METHODS: Dynamic contrast-enhanced ultrasound 12 MHz was used to monitor tumor-bearing Naval Medical Research Institute mice beginning 15 days after tumor implantation. Mice received therapy from 15 to 29 days with sorafenib (N = 9), ziv-aflibercept (N = 11), combined antiangiogenic agents (N = 11), and placebo control (N = 14). Sorafenib (BAY 43-9006; Nexavar), a multikinase inhibitor acting on Raf kinase and receptor tyrosine kinases-including vascular endothelial growth factor receptors 2 and 3-was administered daily (60 mg/kg, per os). Ziv-aflibercept (ZALTRAP), a high-affinity ligand trap blocking the activity of vascular endothelial growth factor A, vascular endothelial growth factor B, and placental growth factor was administered twice per week (40 mg/kg, intraperitoneally). RESULTS: Functional evaluation with dynamic contrast-enhanced ultrasound indicated stable tumor vascularization for the control group while revealing significant and sustained reduction after 1 day of therapy in the combined group (P = .007). There was no survival benefit or penalty due to drug combination. The functional progression-free survival assessed with dynamic contrast-enhanced ultrasound was significantly higher for the 3 treated groups; whereas, the progression-free survival based on tumor size did not discriminate therapeutic effect. CONCLUSIONS: Dynamic contrast-enhanced ultrasound, therefore, presents strong potential to monitor microvascular modifications during antiangiogenic therapy, a key role to monitoring antiangiogenic combining therapy to adapt dose range drug.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Medios de Contraste/administración & dosificación , Aumento de la Imagen/métodos , Neoplasias Experimentales/patología , Neovascularización Patológica/patología , Neoplasias Pancreáticas/patología , Ultrasonografía/métodos , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Desnudos , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/tratamiento farmacológico , Neovascularización Patológica/diagnóstico por imagen , Neovascularización Patológica/tratamiento farmacológico , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Curva ROC , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Sorafenib/administración & dosificación , Resultado del Tratamiento , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Expert Rev Anticancer Ther ; 20(11): 939-945, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32936674

RESUMEN

INTRODUCTION: Tumor control and survival of patients with metastatic pancreatic ductal adenocarcinoma (PDAC) has improved with more effective polychemotherapies. The identification of novel therapeutic targets is strongly needed in order to propose maintenance therapies that improve quality of life while maintaining tumor control. AREAS COVERED: PDAC with mutations in homologous recombination repair genes such as BRCA are particularly sensitive to platinum agents. Recently, the potential role of poly(ADP-ribose) polymerase (PARP) inhibitors was suggested. The POLO study has shown that olaparib was efficient and well-tolerated as maintenance therapy in patients with germline BRCA1/2 mutation and a metastatic PDAC controlled after a platinum-based induction chemotherapy. EXPERT OPINION: The demonstration of olaparib efficacy in patients with metastatic PDAC and BRCA germline mutation has paved the way for maintenance with a targeted therapy. Further studies are needed to assess; the potential role for PARPI in earlier forms of PDAC, those with somatic or more rare BRACness signatures, to overcome primary or secondary resistances to PARPi, and to combine them with other antitumoral agents.


Asunto(s)
Carcinoma Ductal Pancreático/tratamiento farmacológico , Neoplasias Pancreáticas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Animales , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Resistencia a Antineoplásicos , Mutación de Línea Germinal , Humanos , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Calidad de Vida , Tasa de Supervivencia
13.
Mol Clin Oncol ; 10(3): 387-390, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30847179

RESUMEN

Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with a chemical structure characterized by three fused tetrahydroisoquinoline rings. In the present case report, two patients with advanced and metastatic uterine leiomyosarcomas (ULMS) with significant progression-free survival (PFS) and overall survival (OS) administered Trabectedin as second and third line treatment are reported. The first case received third line Trabectedin with a PFS of 24 months and an OS of 35 months. The second case received second line Trabectedin with a PFS of 24 months and an OS of 30 months. In addition, a good safety record was obtained in the long-term administration of Trabectedin (more so in case 1 than case 2), with a good quality of life.

15.
Ann Surg Oncol ; 15(11): 3222-6, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18709415

RESUMEN

BACKGROUND: The role of radiofrequency (RF) ablation to treat local recurrence of breast cancer is unknown. METHODS: We conducted a two-stage phase II clinical trial. Eligible patients had a histologically confirmed noninflammatory and < or =3 cm ipsilateral breast tumor recurrence. The tumor site was identified by intraoperative sonography. A LeVeen needle electrode (RadioTherapeutics Corp, Mountain View, Calif) was inserted into a single site within the tumor and radiofrequency ablation was performed using a RF-2000 generator (RadioTherapeutics Corp). After completion of radiofrequency, a mastectomy was performed. Conventional staining and nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) cell viability staining were performed. RESULTS: During the first stage, procedures were uneventful. Conventional, cytokeratin, and NADH-diaphorase staining identified persistent viable tumor cells in the RF-ablated region in three patients. This phase II trial was stopped after completion of the first stage because of insufficient efficacy. CONCLUSION: We demonstrate in this study that RF ablation is a potential technique to destroy local recurrence of breast tumors but the technique we tested in this phase II clinical trial had insufficient efficacy to recommend its use in routine.


Asunto(s)
Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/cirugía , Ablación por Catéter/métodos , Ganglios Linfáticos/patología , Recurrencia Local de Neoplasia/cirugía , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/diagnóstico por imagen , Carcinoma Ductal de Mama/patología , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Femenino , Humanos , Escisión del Ganglio Linfático , Mastectomía Simple , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Biopsia del Ganglio Linfático Centinela , Ultrasonografía Mamaria
16.
Clin Cancer Res ; 13(6): 1801-9, 2007 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-17363536

RESUMEN

PURPOSE: To determine the safety, maximum tolerated dose, pharmacokinetics, and efficacy, and to evaluate biomarkers, of the multikinase inhibitor sorafenib plus IFN alpha-2a in advanced renal cell carcinoma (RCC) or melanoma. EXPERIMENTAL DESIGN: Patients received 28-day cycles of continuous, oral sorafenib twice daily and s.c. IFN thrice weekly: sorafenib 200 mg twice daily plus IFN 6 million IU (MIU) thrice weekly (cohort 1); and sorafenib 400 mg twice daily plus IFN 6 MIU thrice weekly (cohort 2); or plus IFN 9 MIU thrice weekly (cohort 3). Tumor response was assessed by Response Evaluation Criteria in Solid Tumors and dynamic contrast-enhanced ultrasonography. RESULTS: Thirteen patients received at least one dose of sorafenib plus IFN (12 RCC; one melanoma). The maximum tolerated dose was not reached [only one dose-limiting toxicity (grade 3 asthenia)]. Most frequently reported drug-related adverse events were grade 2 or less in severity, including fatigue, diarrhea, nausea, alopecia, and hand-foot skin reaction. One (7.7%) RCC patient achieved partial response and eight (61.5%) had stable disease (including the melanoma patient). Good responders assessed by dynamic contrast-enhanced ultrasonography had increased progression-free survival and overall survival, relative to poor responders. IFN had no effect on the pharmacokinetics of sorafenib. There were no significant changes in absolute values of lymphocytes, levels of proangiogenic cytokines, or inhibition of phosphorylated extracellular signal-regulated kinase in T cells or natural killer cells, with combination therapy. CONCLUSIONS: This sorafenib combination was well tolerated, with preliminary antitumor activity in advanced RCC and melanoma patients. There were no drug-drug interactions and the recommended dose for future studies is sorafenib 400 mg twice daily plus IFN 9 MIU.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencenosulfonatos/administración & dosificación , Carcinoma de Células Renales/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Neoplasias Renales/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Piridinas/administración & dosificación , Adulto , Anciano , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Bencenosulfonatos/efectos adversos , Bencenosulfonatos/farmacocinética , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/patología , Femenino , Humanos , Sistema Inmunológico/efectos de los fármacos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/farmacocinética , Neoplasias Renales/patología , Masculino , Melanoma/patología , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Piridinas/farmacocinética , Proteínas Recombinantes , Sorafenib , Resultado del Tratamiento
17.
Mol Clin Oncol ; 9(1): 96-97, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29896404

RESUMEN

Metastasis of non-gynaecological tumours to the cervix is a rare event, and metastasis from breast cancer is even rarer, with only a limited number of such cases reported in the literature to date. We herein report the case of an 86-year-old female patient who had undergone mastectomy and axillary lymphadenectomy for invasive ductal cell breast carcinoma 2 years prior, followed by adjuvant hormonal therapy with letrozole. During hospitalization for anemia associated with an inflammatory syndrome and abdominal pain with menorrhagia, an abdominal ultrasound examination revealed a suspicious uterine mass with irregular contours and abnormal vascularization with associated increase of the blood level of cancer antigen 15-3 to 34 kU/l. The histological and immunohistochemical analysis of a cervical biopsy sample discover a secondary lesion metastatic from the primary ductal cell breast carcinoma. The metastatic tissue was hormone-negative, which was compatible with disease progression during hormonal therapy. Considering the multiple metastasis, comorbidities, unfavourable performance status and the quick deterioration of the patient's clinical condition, only best supportive care was administered.

18.
Eur J Cancer ; 42(15): 2472-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16965911

RESUMEN

INTRODUCTION: The objective of this study was to evaluate dynamic contrast-enhanced Doppler ultrasound (DCE-US) with perfusion software (Vascular Recognition Imaging) and contrast agent injection as a predictor of tumour response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Thirty patients with a metastatic renal cell carcinoma (RCC) already enrolled in a double-blind randomised study were evaluated. Examinations were performed at baseline, and after 3 and 6 weeks on sorafenib or a placebo in patients with tumour targets that were accessible to DCE-US. RESULTS: A total of 85 examinations were performed, 30 at baseline, 28 at 3 weeks and 27 at 6 weeks. The combination of a decrease in contrast uptake exceeding 10% and stability or a decrease in tumour volume allowed us to discriminate seven good responders and 20 poor responders at 3 weeks. There was a statistically significant difference in PFS (p=10(-4)) and OS (p=10(-4)) between good and poor responders. CONCLUSION: DCE-US is a new noninvasive imaging technique which might be an effective tool for evaluating antiangiogenic drugs in renal cancer.


Asunto(s)
Carcinoma de Células Renales/diagnóstico por imagen , Neoplasias Renales/diagnóstico por imagen , Ultrasonografía Doppler/métodos , Adulto , Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Medios de Contraste , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Método Doble Ciego , Femenino , Humanos , Neoplasias Renales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Fosfolípidos , Proyectos Piloto , Piridinas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sorafenib , Hexafluoruro de Azufre , Análisis de Supervivencia , Resultado del Tratamiento
19.
AJR Am J Roentgenol ; 187(5): 1267-73, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17056915

RESUMEN

OBJECTIVE: The purpose of this study was to evaluate contrast-enhanced Doppler sonography with perfusion software as a predictor of early tumor response to imatinib (Glivec) in c-kit-positive gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS: Thirty patients (59 tumors) with metastases or a recurrence from a GIST were prospectively included in a single-center imaging trial. Contrast-enhanced Doppler sonography was performed with an Aplio scanner the day before (day-1) starting oral treatment (400 mg) and at days 1, 7, 14, 60, 90, and 6 months, 9 months, and 1 year. The percentage of contrast uptake (Levovist or Sonovue) before treatment and at the different stages of follow-up was evaluated by two radiologists. Digitized quantification was performed using Photoshop software. To define the benchmark standard, all patients were rated as responders or nonresponders at 2 and 6 months by a board consisting of oncologists and radiologists who had all clinical and imaging data at their disposal. Changes in the percentage of contrast uptake at each sonographic examination were compared statistically. RESULTS: A total of 185 examinations were performed. Forty-four lesions in 24 patients were completely evaluated at 2 months, and 29 lesions in 15 patients were completely evaluated at 6 months. Initial contrast uptake at day 1 was predictive of the future response. A strong correlation was found between the decline in tumor contrast uptake at days 7 and 14 and tumor response (p < 10(-4)). CONCLUSION: Contrast-enhanced Doppler sonography is a noninvasive imaging technique that allows the early prediction of tumor response in c-kit-positive GIST treated with Glivec.


Asunto(s)
Antineoplásicos/uso terapéutico , Medios de Contraste , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Piperazinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Benzamidas , Femenino , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/metabolismo , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Fosfolípidos , Polisacáridos , Pronóstico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-kit/metabolismo , Hexafluoruro de Azufre , Ultrasonografía Doppler
20.
Eur J Radiol ; 56(3): 376-81, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16005593

RESUMEN

INTRODUCTION: The aim of this study was to determine the efficacy of Doppler ultrasonography (US) with perfusion software and contrast agent injection (DUPC) during radiofrequency (RF) treatment of local recurrent breast cancer. MATERIALS AND METHODS: Ten patients were included in this monocentric prospective phase II study. DUPC was performed for each patient the day before treatment and immediately after RF in the operating suite. RF ablation was followed by a total mastectomy. The results of DUPC were compared to the histologic analysis of the operative specimen. RESULTS: Before RF, contrast uptake exceeded 70% in 5 lesions and was less than 50% in 5 lesions. Immediately after RF, no vascularization was detected with DUPC in 9 of the 10 lesions. Contrast uptake attaining 30% was depicted in the remaining lesion. At histologic analysis, complete tumour destruction was confirmed in 7 of the 10 operative specimens. CONCLUSION: In this study, DUPC is highly efficient and better adapted for the confirmation of tumour destruction in tumours that are hypervascularised before RF compared to hypovascularised lesions.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Ablación por Catéter/métodos , Recurrencia Local de Neoplasia/diagnóstico por imagen , Fosfolípidos , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Programas Informáticos , Hexafluoruro de Azufre , Ultrasonografía Doppler en Color/métodos , Adulto , Anciano , Neoplasias de la Mama/cirugía , Medios de Contraste , Femenino , Humanos , Inyecciones Intravenosas , Persona de Mediana Edad , Perfusión/métodos , Proyectos Piloto , Cuidados Posoperatorios/métodos , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del Tratamiento
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