RESUMEN
BACKGROUND: At 42.5 months of median follow-up, PHARE failed to show that 6 was non-inferior to 12 months of adjuvant trastuzumab. From the results of PHARE, questions remain regarding whether the magnitude of benefit derived from 1 year is sufficient to justify its systematic use for different patient subgroups. METHODS: Treatment effects were evaluated according to various tumour characteristics, and the multivariate Cox proportional hazards regression models were carried out on metastases-free survival (MFS) in the 12 months control arm. A prognostic score was defined providing the identification of patient categories with similar risks. The 6-month arm was used as a validation set in order to test for heterogeneity. This study is registered at clinicaltrials.gov, number NCT00381901. RESULTS: A total of 261 metastatic events were observed and four prognostic groups were defined: very low, low, intermediate and high risk in the 12-month arm. The corresponding 3-year MFS rates were 98.3%, 95.8%, 90.4% and 78.4% in the four prognostic groups, respectively. In the 6-month arm, the 3-year MFS rates were 98.3%, 94.2%, 85.7% and 74.8% in the four prognostic groups, respectively. CONCLUSION: In the very low-risk group, the potential absolute benefit of standard duration of trastuzumab was small enough to indicate that optimal standard treatment might be clinically questionable. On the other hand, the 3-year metastasis occurrence rates strongly support the need for a search of a more efficient treatment in the low-, intermediate- and high-risk groups.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante , Femenino , Francia/epidemiología , Humanos , Metástasis Linfática , Persona de Mediana Edad , Metástasis de la Neoplasia , Receptor ErbB-2/metabolismo , Análisis de Supervivencia , Trastuzumab , Carga TumoralRESUMEN
Based on nationwide data from the French national cancer institute (INCa), we analyzed the evolution of cancer genetics consultations and testing over time, and the uptake of targeted tests in relatives of families with BRCA1/2 or MMR genes mutation. Genetic testing and consultations for familial high-risk individuals are exclusively funded and monitored by the INCa in France. All nationwide cancer genetics centers reported annually standardized parameters of activity from 2003 to 2011. The analysis included a total of 240,134 consultations and 134,652 genetic tests enabling to identify 32,494 mutation carriers. Referral for hereditary breast and ovarian cancer (HBOC) or colorectal cancer predisposition syndromes represented 59 % (141,639) and 23.2 % (55,698) consultations, respectively. From 2003 to 2011, we found a dramatic and steady increase of tests performed for BRCA1/2 (from 2,095 to 7,393 tests/year, P < 0.0001) but not for MMR genes (from 1,144 to 1,635/year, P = NS). The overall percentage of deleterious mutations identified in the probands tested was 13.8 and 20.9 % in HBOC and Lynch syndromes, respectively. Pooled analysis for BRCA1/2 and Lynch syndrome tests showed an inverse relationship between the percentage of mutation detected and the absolute number of tests performed over the time (overall Cochran-Armitage test for trend: P < 0.001). In families with BRCA1/2 or MMR identified mutations, there was an average number of 2.94 and 3.28 relatives performing targeted tests, respectively. This nationwide study shows a lack of referral and genetic testing in Lynch as compared to HBOC syndromes. Only a third of relatives of a proband with a predisposing mutation performed a targeted test. Enhanced information about benefit of genetic testing should be given to clinicians and patients for Lynch syndrome and relatives of a proband carrying an identified predisposing mutation.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de la Mama/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Proteínas de Unión al ADN/genética , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético/estadística & datos numéricos , Pruebas Genéticas/estadística & datos numéricos , Proteína 2 Homóloga a MutS/genética , Síndromes Neoplásicos Hereditarios/genética , Proteínas Nucleares/genética , Neoplasias Ováricas/genética , Derivación y Consulta/estadística & datos numéricos , Neoplasias de la Mama/prevención & control , Instituciones Oncológicas/estadística & datos numéricos , Neoplasias Colorrectales Hereditarias sin Poliposis/prevención & control , Reparación de la Incompatibilidad de ADN/genética , Análisis Mutacional de ADN/estadística & datos numéricos , Salud de la Familia , Femenino , Francia , Tamización de Portadores Genéticos , Asesoramiento Genético/tendencias , Pruebas Genéticas/tendencias , Humanos , Laboratorios/estadística & datos numéricos , Masculino , Homólogo 1 de la Proteína MutL , Mutación , Síndromes Neoplásicos Hereditarios/prevención & control , Neoplasias Ováricas/prevención & control , Derivación y Consulta/tendenciasRESUMEN
Treatment options for radioiodine resistant metastatic thyroid cancer patients are limited, and chemotherapy is considered an outdated therapeutic method for differentiated thyroid carcinoma. In this study, we evaluated the activity and safety of gemcitabine and oxaliplatin combination which is considered an out of label therapeutic method in patients with differentiated metastatic thyroid cancer refractory to 131-I treatment. Fourteen refractory patients (8 papillary, 6 follicular), six men/eight women with median age of 63 years and performance status (0-3) were included. Patients received gemcitabine (1,000 mg/m(2)) plus oxaliplatin (100 mg/m(2)) every 2 weeks until 12-cycles and each cycle correspond to 2 weeks treatment. This protocol was approved by the local Institutional Review Boards. Response rate was assessed every four cycles. Progression-free and overall survivals were calculated. Median treatment was 9.5 cycles (range 2-17) with 22 weeks duration. Overall response rate was 57%, with 7% achieving a complete response (1/14), 50% a partial response (7/14), and 28% with a stable disease. All patients with follicular subtype showed objective responses. Eleven patients progressed at a median time of 10.1 months; 10 of 14 patients still alive and the median survival was not reached (median follow-up of 19.8 months). The combination was generally well tolerated. No deaths occurred due to therapy and no grade IV toxicity was recorded. The most common treatment-related adverse events grade 1/3 includes asthenia, peripheral neuropathy, diarrhea, anemia, thrombocytopenia, and neutropenia. In conclusion, the GEMOX regimen is well tolerated and effective in advanced differentiated thyroid cancer. However, this retrospective data on a small sample size are considered preliminary and needs to be evaluated prospectively in a higher number of patients in a clinical trial.
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Adenocarcinoma Folicular/tratamiento farmacológico , Adenocarcinoma Papilar/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Uso Fuera de lo Indicado , Neoplasias de la Tiroides/tratamiento farmacológico , Adenocarcinoma Folicular/mortalidad , Adenocarcinoma Folicular/patología , Adenocarcinoma Papilar/mortalidad , Adenocarcinoma Papilar/patología , Adulto , Anciano , Anciano de 80 o más Años , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Terapia Recuperativa/métodos , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/patologíaRESUMEN
The treatment of certain cancers has been revolutionised in recent years by the introduction of novel drugs designed to target specific molecular factors implicated in tumour growth. Notable examples include trastuzumab, a humanized monoclonal antibody (mAb) against human epidermal growth factor receptor (HER)-2 in women with HER2-positive breast cancer; rituximab, an anti-CD20 mAb in patients with non-Hodgkin's lymphoma; imatinib, a tyrosine kinase inhibitor in KIT-positive gastrointestinal stromal tumours and sunitinib, another tyrosine kinase inhibitor, in metastatic renal cell carcinoma. For regulatory reasons, new molecular targeted agents are first evaluated in advanced and metastatic disease, wherein they prolong survival. However, their most profound impact has been observed in the adjuvant setting, where they may contribute to curative therapy rather than mere palliation. Expansion in the use of molecular targeted therapies will have important cost implications for health care systems. Although expensive, on a monthly basis, molecular targeted therapies may not be more costly than treatments for other major chronic diseases, especially considering the contribution of cancer to the global disease burden, the associated socioeconomic costs and the long-term benefits of therapy. Nevertheless, the use of these agents must be optimised, in part using molecular biomarkers associated with drug response.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Linfoma no Hodgkin/tratamiento farmacológico , Terapia Molecular Dirigida , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Benzamidas , Biomarcadores Farmacológicos , Femenino , Humanos , Mesilato de Imatinib , Indoles/uso terapéutico , Piperazinas/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-kit/genética , Pirimidinas/uso terapéutico , Pirroles/uso terapéutico , Receptor ErbB-2/inmunología , Rituximab , Sunitinib , TrastuzumabRESUMEN
BACKGROUND: Pancreatic cancer has proven extremely challenging to treat. A collaborative effort is needed to advance research and improve treatment. An expert conference was conducted to elicit perspectives regarding the current treatment and future research of pancreatic cancer. METHODS: The conference comprised an international panel of experts representing five European countries and the United States. RESULTS: Adjuvant radiotherapy is used more frequently in the United States than in Europe. In locally advanced disease, there is now more emphasis on early chemotherapy in both Europe and the United States. In metastatic disease, combination chemotherapy is commonly used in Europe and the United States. This varies by country. Advancing pancreatic research will require improving biorepositories and developing a roadmap to prioritize therapeutic targets in different models. Small randomized phase II trials of both non-selected and enriched patient populations will help identify activity of new agents. Phase III trials should only be initiated in appropriate patients based on strong clinical and biological signals. Developing drugs in the adjuvant setting may be preferable to eliminate some of the challenges of drug development in the advanced disease setting. CONCLUSION: Progress in research combined with encouraging improvements from the past offer hope for the future of pancreatic cancer patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Investigación Biomédica , Neoplasias Pancreáticas/tratamiento farmacológico , Congresos como Asunto , HumanosRESUMEN
The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments are also highlighted.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Resistencia a Antineoplásicos , Receptor ErbB-2/antagonistas & inhibidores , Inhibidores de la Angiogénesis/metabolismo , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales Humanizados , Bevacizumab , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Sinergismo Farmacológico , Femenino , Humanos , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/metabolismo , Receptor ErbB-2/metabolismo , TrastuzumabRESUMEN
BACKGROUND: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases. METHODS: Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested. RESULTS: Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036). CONCLUSION: Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/metabolismo , Proteínas de Neoplasias/metabolismo , Adulto , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Bevacizumab , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Cetuximab , Neoplasias Colorrectales/tratamiento farmacológico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Receptores ErbB/metabolismo , Femenino , Humanos , Irinotecán , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Hypertension (HTN) is one of the most frequent side-effects of systemic inhibition of vascular endothelial growth factor (VEGF) signaling. Its incidence and severity are dependent on the type of drugs, dose, and schedule used. The recognition of this side-effect is an important issue because poorly controlled HTN could lead to serious cardiovascular events. On another hand, HTN induced by anti-VEGF agents maybe a predictive factor of oncologic response. Knowledge of this clinical toxicity and/or therapeutic target or novel biomarker of drug activity can aid clinicians choosing the optimal and least toxic regimen suitable for an individual patient. METHODS: A Medline search was carried out using the following criteria: (i) all Medline listings as of 1 January 2000 with abstracts, (ii) English language, and (iii) Humans. The following phrases were used to query the database: ('hypertension', OR 'blood pressure') AND ('anti-VEGF' OR 'VEGF inhibition' OR 'bevacizumab' OR 'sunitinib' OR 'sorafenib' OR 'VEGF Trap'). The references of each article identified were carefully reviewed for additional reference. RESULTS: Lifestyle modification should be encouraged. However, these nonpharmacologic strategies are not always suitable to patients with altered performance status related to metastatic cancer necessitating early drug intervention. Only one randomized study showed a beneficial effect of a calcium channel blocker use to prevent or minimize HTN secondary to antiangiogenic therapy. Nitrates looks as effective in controlling such side-effect. CONCLUSIONS: No clear recommendation for an antihypertensive agent can be made in this context because there is a lack of controlled studies addressing the subject. Blood pressure-lowering drugs should be individualized to the patient's clinical circumstances and angiogenic inhibitors should be withheld only from patients who experienced hypertensive crisis.
Asunto(s)
Inhibidores de la Angiogénesis/efectos adversos , Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Presión Sanguínea/efectos de los fármacos , Humanos , Hipertensión/inducido químicamente , Hipertensión/fisiopatología , Neoplasias/metabolismo , Selección de Paciente , Guías de Práctica Clínica como Asunto , Medición de Riesgo , Conducta de Reducción del Riesgo , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Two studies were carried out to evaluate heat-killed Mycobacterium vaccae SRL172 as an immunotherapeutic agent for patients with metastatic, post-nephrectomy, renal cell carcinoma. In the first study, 60 patients in France and the UK received injections of SRL172, and their survival was compared with that of historical controls who had been treated either with biological response modifiers (IL-2, IFN-alpha) or chemotherapy. In the second study, 36 patients were randomised to receive treatment with IL-2 alone or IL-2 plus SRL172. Survival and adverse events related to the treatments were assessed and compared between treatment groups. The first study showed that those treated with SRL172 alone survived equally as long as those receiving IL-2 or IFN-alpha and both treatment groups survived longer than those on chemotherapy (p<0.001), a result supported by Cox's proportional hazards regression analysis. The second study, stopped early due to drug supply issues, showed that the addition of SRL172 to IL-2 made no difference to survival compared to IL-2 alone, in the limited numbers treated. Adverse events occurring in those receiving SRL172 in the first study were mild and in the second study those receiving IL-2 alone had significantly more adverse events than those receiving SRL172 plus IL-2 (p<0.001). It is concluded that SRL172 may have activity in metastatic renal cancer and has very low toxicity, making it worthy of further study.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vacunas Bacterianas/uso terapéutico , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Células Renales/terapia , Inmunoterapia/métodos , Neoplasias Renales/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Vacunas Bacterianas/efectos adversos , Vacunas contra el Cáncer/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Interleucina-2/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Inhibitors of epidermal growth factor receptors (EGFR) constitute a new alternative treatment for patients presenting certain advanced stage solid cancers (bowel, breast, ovary). Adverse cutaneous effects of these drugs are now starting to be described. OBSERVATIONS: Our study involved 2 men and 2 women with no previous history of acne included in a treatment protocol comprising EGFR inhibitors. Mean age was 52 years. The primary cancers were breast, ovary, bowel and unidentified. The EGFR inhibitors used were gefitinib (ZD1839) (2 cases), carnetinib (Cl1033) and cetuximab (IMC-C225). Skin lesions appeared after 7 days and included erythematous papules and follicular pustules of the face, back and upper chest. No comedons were seen, and there were no nodules or cysts. The severity of the rash resulted in discontinuation of treatment in 2 patients with complete disappearance of skin lesions in both cases. In one patient, reduction of the dosage of gefitinib (IMC-C225) led to gradual resolution of the rash. Histological examination of papules and pustules concluded on an acute suppurative folliculitis. Smears and cultures ofa nasal lesion and pustules revealed coagulase-positive Staphylococcus aureus in 2 patients. Combined doxycycline 100 mg daily and benzoyl peroxide was prescribed for 3 months and a favourable outcome was achieved after a mean 2 weeks. DISCUSSION: EGFR inhibitors act by inhibiting mechanisms oftumour proliferation in certain cancers at advanced stages or refractory to other treatments. Our findings in these four patients are similar to the published cases in terms of rapid onset of monomorphous, papulopustular, follicular eruption without comedons. Rapid response to cyclines and benzoyl peroxide is also reported in literature. This treatment must be instituted rapidly and patients must be informed about the cutaneous side-effects of EGFR inhibitors before the start of therapy. The pathophysiology of these eruptions is still unknown. Skin signs are probably due to interaction with EGFR functions, including overexpression of EGFR in keratinocytes and hair follicles.
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Antineoplásicos/efectos adversos , Erupciones por Medicamentos/etiología , Receptores ErbB/antagonistas & inhibidores , Adulto , Antineoplásicos/administración & dosificación , Femenino , Foliculitis/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
BACKGROUND: Delayed emesis following chemotherapy in cancer patients remains an important challenge for treatment and contributes to poor quality of life and treatment compliance. OBJECTIVES: To compare the efficacy and tolerability of associations of metopimazine and ondansetron with methylprednisolone for the prevention of delayed chemotherapy-induced nausea and emesis. METHODS: A randomised, open-label, observational, cross-over design was used to compare two treatment strategies following two consecutive sessions of chemotherapy separated by at least 1 week. Patients were randomised to treatment with sublingual metopimazine (15 mg tid) or ondansetron lyophilisate (8 mg bid) for 5 days. All patients received oral methylprednisolone (48 mg). Patients reported episodes of nausea and emesis in a diary, and completed the Functional Living Index Emesis quality of life questionnaire. Adverse events were also evaluated. RESULTS: Ninety-nine patients were included in the study, 79.5% of whom were women, with a mean age of 52.7 years. Breast cancer was the most common individual cancer and most patients were receiving combinations of cytotoxic drugs. Treatment was successful at preventing delayed emesis in 73.6% of patients during treatment with the metopimazine-methylprednisolone association and 57.5% during the ondansetron-methylprednisolone association. Analysis of discordant pairs revealed a significant benefit in favour of the methopimazine-methylprednisolone association (p = 0.006). No significant difference was observed between treatments for the overall quality of life score. The incidence of gastrointestinal disorders, particularly constipation, was significantly higher during ondansetron-methylprednisolone treatment (p = 0.0112). CONCLUSION: Methopimazine is an effective and well-tolerated alternative to setrons for the treatment of delayed nausea and emesis in patients undergoing chemotherapy.
Asunto(s)
Antieméticos/uso terapéutico , Antineoplásicos/efectos adversos , Ácidos Isonipecóticos/uso terapéutico , Metilprednisolona/uso terapéutico , Ondansetrón/uso terapéutico , Vómitos/tratamiento farmacológico , Adulto , Anciano , Antieméticos/efectos adversos , Antineoplásicos/uso terapéutico , Estudios Cruzados , Quimioterapia Combinada , Femenino , Humanos , Ácidos Isonipecóticos/efectos adversos , Masculino , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Náusea/tratamiento farmacológico , Náusea/etiología , Neoplasias/tratamiento farmacológico , Ondansetrón/efectos adversos , Calidad de Vida , Encuestas y Cuestionarios , Vómitos/etiologíaRESUMEN
Epidermal growth factor receptor (EGFR) belongs to a family of receptors known as the ErbB family (ErbB tyrosine kinase receptors) which comprises four proteins encoded by the c-erbB proto-oncogene. EGFR is known to activate a cascade of multiple signaling pathways that facilitate tumor growth process. EGFR has been shown to be overexpressed in colorectal cancer patient populations but its prognostic value in colorectal cancer progression remains unclear. The development of a panel of EGFR inhibitors could reduce the proliferation of tumor cells when used alone or in combination with cytotoxic drugs or radiation. This review focuses on the potential role of EGFR signaling in the survival of colorectal tumor cells and the possible modulation of such signaling pathways by EGFR inhibitors so as to increase tumor control or render tumor cells more sensitive to conventional therapy.
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Neoplasias Colorrectales/fisiopatología , Receptores ErbB/fisiología , Transducción de Señal , Proliferación Celular , Supervivencia Celular , Neoplasias Colorrectales/terapia , Receptores ErbB/antagonistas & inhibidores , Humanos , Pronóstico , Proto-Oncogenes MasRESUMEN
BACKGROUND: Epidermal growth factor receptor (EGFR) is overexpressed in many types of cancers, especially colorectal cancer (CRC), and seems to reflect more aggressive histological and clinical behaviors. The aim of this study was to evaluate EGFR immunohistochemical reactivity in CRC biopsies, and to analyze its relationship with various histological and clinical characteristics and survival. PATIENTS AND METHODS: A composite EGFR score, obtained by multiplying the grade (% positive cells) by the intensity of labeling (0-9) was used to define patients with low or high EGFR expression whose clinicopathological features were then compared. Univariate tests and multivariate Cox proportional hazards model were applied for data analysis. RESULTS: Tissue sections from 150 CRC patients with a median follow-up of 40 months were examined. Median patient age at diagnosis was 70 years (range 38-89 years). EGFR reactivity was positive for 143 patients (97%) and high for 118 (80%). According to multivariate analysis, EGFR overexpression was significantly associated with tumor stage, with a higher percentage of EGFR overexpression in T3 than T4 (P=0.003) and not with overall survival. CONCLUSIONS: EGFR was overexpressed in this CRC patient population and was significantly associated with TNM (tumor-node-metastasis) stage T3. In the context of a new therapeutic strategy using EGFR-targeted therapies, although EGFR remains a controversial prognostic factor, this expression-stage association may play a crucial role in a decision to initiate an adjuvant treatment.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Receptores ErbB/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Toma de Decisiones , Receptores ErbB/análisis , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Análisis de SupervivenciaRESUMEN
GOALS OF WORK: The aim of the study was to measure taste thresholds among cancer patients under chemotherapy compared to controls. PATIENTS AND METHODS: The study was performed with 110 cancer patients and 170 healthy subjects of similar age distribution were included in the study. The electrogustometric detection threshold was evaluated as the lowest current intensity perceived by the subject in three tongue sites independently with a constant current generator. MAIN RESULTS: Taste thresholds for all cancer patients demonstrated significantly higher values compared to controls. CONCLUSIONS: Cancer patients treated by chemotherapy demonstrated a temporary taste sensitivity deficit. Associated with the illness due to the treatment, this deficit explains the patients complaining of "abnormal or bad tastes", which results in food aversion and has a negative impact on nutritional status and quality of life. In order to prevent the risk of anorexia and the enhanced morbidity related to this deficit, treatment should include relevant information to the subject for anticipating objective taste modifications and a psychological follow-up during the actual change of taste quality perceptions in everyday life.
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Antineoplásicos/efectos adversos , Trastornos del Gusto/inducido químicamente , Umbral Gustativo , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Estudios de Casos y Controles , Conducta Alimentaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Calidad de VidaRESUMEN
BACKGROUND: The expression of CXCR4 has been implicated in metastatic dissemination in different models of breast cancer and melanoma. In the present study, we evaluated CXCR4 expression in non-small-cell lung cancer (NSCLC) and the relationship between CXCR4 expression and the prognosis of stage I disease. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed CXCR4 expression in specimens from 61 patients with completely resected pathologically confirmed stage I NSCLC for whom clinical follow-up data were available. RESULTS: In the present study, we have shown that: CXCR4 is expressed by tumor cells in stage I NSCLC; CXCR4 is located in the nucleus and/or in the cytoplasm of tumor cells; strong nuclear staining was observed in 17 cases (29.8%); patients whose tumors had CXCR4-positive nuclear staining had a significantly longer duration of survival than patients whose tumors had no nuclear expression (P = 0.039, log-rank test). Interestingly, the 5-year metastasis rates were 23.5% and 34.1% in patients with CXCR4-positive and CXCR4-negative nuclear expression, respectively (P = 0.2). CONCLUSION: Strong CXCR4-positive nuclear staining was associated with a significantly better outcome in early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Receptores de Quimiocina/análisis , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Receptores CCR4 , Análisis de Supervivencia , Tasa de SupervivenciaRESUMEN
Malignant melanoma is one of the most worrisome tumors in terms of epidemiology, and incidence is increasing. The estimated lifetime risk in the United States is 1 in 75 people. As soon as the first distant metastasis appears, the disease becomes one of the most aggressive and chemoresistant tumors: 90-95% of patients do not survive more than 3 years. Results with chemotherapy are disappointing as few drugs have demonstrated an impact on survival. Drug combinations provide only a slightly higher response rate and do not overcome the natural chemoresistance of this tumor. Tamoxifen, which was widely investigated in the late 1980s and 1990s, has not added any benefit in terms of response rate or survival. Since their description as immunomodulating molecules, the cytokines interferon-alpha and interleukin-2 (IL-2) have been extensively tested in malignant melanoma. They seem to achieve higher response rates and survival rates than chemotherapy but undoubtedly lead to more long-term unmaintained remissions. Their combination with chemotherapeutic drugs, "chemoimmunotherapy", has been tested using various doses and schedules (one or two cytokines, single drug or combination chemotherapy). The combination of cisplatin and IL-2 plays a key role in this strategy. However, because of its higher toxicity, the real benefit of chemoimmunotherapy on patient survival still needs to be proven.
Asunto(s)
Melanoma/terapia , Antineoplásicos/uso terapéutico , Terapia Combinada , Humanos , Inmunoterapia , Melanoma/inmunología , Melanoma/secundario , Ensayos Clínicos Controlados Aleatorios como Asunto , Tamoxifeno/uso terapéuticoRESUMEN
Interleukin-1beta converting enzymes (ICEs/caspases) are involved in programmed cell death (apoptosis). This study sought to quantify the caspase-1 level in metastatic malignant melanoma patients and to try to establish a correlation between the level of caspase-1 and different parameters related to this pathology. In addition, we evaluated the possible relationship between the clinical response to biochemotherapy and the caspase-1 level. The serum caspase-1 level was determined in 81 metastatic malignant melanoma patients and 50 normal volunteers using enzyme-linked immunosorbent assay (ELISA). Patients received cisplatin, recombinant interleukin-2 (Proleukin) and alpha-interferon (Roferon A) in two induction cycles, and assessment of clinical response was performed according to World Health Organization (WHO) criteria. The median caspase-1 level in melanoma patients was significantly higher (P = 0.0035) than in control samples. Interestingly, a positive correlation between caspase-1 level and the tumour burden was shown (rs = 0.629, P = 0.009). When the clinical response was taken into consideration, the level of caspase-1 was significantly higher in biochemorefractory patients compared with responding ones (P = 0.04). After treatment, the caspase-1 level remained very high in biochemorefractory patients, while in responding ones no change was observed. Furthermore, a positive correlation between the clinical response and the caspase-1 level was established (rs = 0.404, P = 0.024). In conclusion, we observed an elevated caspase-1 level in metastatic malignant melanoma patients. In addition, the correlations obtained between the caspase-1 level and both the tumour burden and the clinical response to the treatment support the concept that disrupted apoptosis pathways might be involved in the progressive disease of advanced melanoma and/or may confer resistance to treatment.
Asunto(s)
Apoptosis , Caspasa 1/sangre , Resistencia a Antineoplásicos , Melanoma/enzimología , Proteínas de Neoplasias/sangre , Adulto , Anciano , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Caspasa 1/fisiología , Cisplatino/uso terapéutico , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Interferón-alfa/uso terapéutico , Interleucina-2/uso terapéutico , L-Lactato Deshidrogenasa/sangre , Masculino , Melanoma/tratamiento farmacológico , Melanoma/patología , Persona de Mediana Edad , Metástasis de la Neoplasia , Proteínas de Neoplasias/fisiología , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m(2) every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m(2) every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m(2) (range, 150 to 543 mg/m(2)), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Taxoides , Adulto , Anciano , Neoplasias de la Mama/patología , Ciclofosfamida/administración & dosificación , Docetaxel , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Paclitaxel/análogos & derivados , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.