RESUMEN
BACKGROUND: The European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS) has been accepted as a robust tool to evaluate the magnitude of clinical benefit reported in trials for oncological therapies. However, the ESMO-MCBS hitherto has only been validated for solid tumours. With the rapid development of novel therapies for haematological malignancies, we aimed to develop an ESMO-MCBS version that is specifically designed and validated for haematological malignancies. METHODS: ESMO and the European Hematology Association (EHA) initiated a collaboration to develop a version for haematological malignancies (ESMO-MCBS:H). The process incorporated five landmarks: field testing of the ESMO-MCBS version 1.1 (v1.1) to identify shortcomings specific to haematological diseases, drafting of the ESMO-MCBS:H forms, peer review and revision of the draft based on re-scoring (resulting in a second draft), assessment of reasonableness of the scores generated, final review and approval by ESMO and EHA including executive boards. RESULTS: Based on the field testing results of 80 haematological trials and extensive review for feasibility and reasonableness, five amendments to ESMO-MCBS were incorporated in the ESMO-MCBS:H addressing the identified shortcomings. These concerned mainly clinical trial endpoints that differ in haematology versus solid oncology and the very indolent nature of nevertheless incurable diseases such as follicular lymphoma, which hampers presentation of mature data. In addition, general changes incorporated in the draft version of the ESMO-MCBS v2 were included, and specific forms for haematological malignancies generated. Here we present the final approved forms of the ESMO-MCBS:H, including instructions. CONCLUSION: The haematology-specific version ESMO-MCBS:H allows now full applicability of the scale for evaluating the magnitude of clinical benefit derived from clinical studies in haematological malignancies.
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Antineoplásicos , Neoplasias Hematológicas , Linfoma Folicular , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Oncología Médica , Neoplasias Hematológicas/terapia , Sociedades Médicas , Linfoma Folicular/tratamiento farmacológico , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with â¼4 years of additional study follow-up. PATIENTS AND METHODS: ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib. CONCLUSIONS: These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Anaplásico de Tiroides , Neoplasias de la Tiroides , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Imidazoles/uso terapéutico , Mutación , Oximas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , Piridonas/uso terapéutico , Pirimidinonas/uso terapéutico , Carcinoma Anaplásico de Tiroides/tratamiento farmacológico , Carcinoma Anaplásico de Tiroides/genética , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/genéticaRESUMEN
Body mass index (BMI) is a prognostic factor in several cancer types. We investigated the prognostic role of BMI in a large patient cohort with newly diagnosed lung cancer brain metastases (BM) between 1990 and 2013. BMI at diagnosis of BM and graded prognostic assessment (GPA) were calculated. Definitions were underweight (BMI <18.50), weight within normal range (BMI 18.50-24.99) and overweight (BMI ≥ 25.00). A total of 624 patients (men 401/624 [64.3%]; women 223/624 [35.7%]; median age of 61 [range 33-88]) were analysed. Histology was non-small cell lung cancer in 417/622 (66.8%), small cell lung cancer (SCLC) in 205/624 (32.9%) and not otherwise specified in 2/624 (0.3%) patients. About 313/624 (50.2%) had normal BMI, 272/624 (43.5%) were overweight and 39/624 (6.3%) were underweight. Underweight patients had shorter median overall survival (3 months) compared to patients with normal BMI (7 months) and overweight (8 months; p < .001; log rank test). At multivariate analysis, higher GPA class (HR 1.430; 95% cumulative incidence, CI 1.279-1.598; p < .001; Cox regression model), SCLC histology (HR 1.310; 95% CI 1.101-1.558) and presence of underweight (HR 1.845; 95% CI 1.317-2.585; p = .014; Cox regression model) were independent prognostic factors. Underweight at diagnosis of BM in lung cancer is associated with an unfavourable prognosis.
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Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Neoplasias Pulmonares/mortalidad , Sobrepeso/epidemiología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Delgadez/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Carcinoma de Pulmón de Células no Pequeñas/secundario , Comorbilidad , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Carcinoma Pulmonar de Células Pequeñas/secundario , Tasa de SupervivenciaRESUMEN
We aimed to analyse the impact of breast cancer (BC) subtypes on the clinical course of disease with special emphasis on the occurrence of brain metastases (BM) and outcome in an elderly BC population. A total number of 706 patients ≥65 years receiving treatment for BC from 2007 to 2011 were identified from a BC database. 62 patients diagnosed with DCIS and 73 patients with incomplete datasets were excluded, leaving 571 patients for this analysis. Patient characteristics, biological tumour subtypes, and clinical outcome including overall survival (OS) were obtained by retrospective chart review. 380/571 (66, 5 %) patients aged 65-74 years were grouped among the young-old, 182/571 (31.9 %) patients aged 75-84 years among the old-old, and 29/571 (5.1 %) patients aged ≥85 years among the oldest-old. 392/571 (68.8 %) patients presented with luminal BC, 119/571 (20.8 %) with HER2-positive, and 59/571 (10.3 %) with triple-negative BC (TNBC). At 38 months median follow-up, 115/571 (20.1 %) patients presented with distant recurrence. A higher recurrence rate was observed in the HER2-positive subtype (43/119 (36.1 %)), as compared to TNBC (15/59 (25.4 %)) and luminal BC (57/392 (14.5 %); p < 0.001). BM were detected at a significantly higher rate in HER2-positive BC patients (9/119 (7.6 %)), as compared to TNBC (2/59 (3.4 %)) and luminal BC patients (6/392 (1.5 %); p = 0.003). Diagnosis of metastatic disease (HR 7.7; 95 % CI 5.2-11.4; p < 0.001) as well as development of BM (HR 3.5; 95 % CI 1.9-6.4; p < 0.001) had a significantly negative impact on OS in a time-dependent covariate cox regression model. In contrast to younger BC patients, outcome in this large cohort of elderly patients suggests that HER2-positive disease-not TNBC-featured the most aggressive clinical course with the highest rates of metastatic spread and BM. In-depth analysis regarding a potentially distinct biology of TNBC in elderly is therefore warranted.
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Neoplasias Encefálicas/secundario , Neoplasias de la Mama/clasificación , Receptor ErbB-2/metabolismo , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: In the United States, there will be a shortage of medical oncologists (MO) by 2020. However, this information is not available for Europe. The aim of this study was to assess the current number of MO in the 27 European Union (27-EU) countries and to predict their availability by 2020. MATERIAL AND METHODS: Between June 2012 and January 2013, a survey was submitted to health authorities, medical oncology societies, and personal contacts in all 27-EU countries in order to gather annual data on the number of practicing MO. Data were collected by e-mail, telephone contact, or through research on official websites. Data regarding cancer incidence in 2008 and projections for 2015 and 2020 were obtained through Globocan. The mean annual increase in the number of MO was calculated for each country. The total number of MO by 2015 and 2020 was estimated, and the ratio of new cancer cases versus number of MO was calculated for 2008, 2015, and 2020. RESULTS: Twelve countries provided sufficient data. The average mean annual increase in the total number of MO was 5.3% (range 1.8%-8.7%), with Belgium being the lowest and UK the highest. The 2008 ratio of cancer cases versus MO was lowest in Hungary (113) and highest in UK (1067). A favorable decrease in this ratio was estimated in most countries. CONCLUSION: Our estimates, based on incidence and not on prevalence, indicate that MO availability will probably meet the projected need in most of the 12 countries analyzed, provided that: (i) these countries maintain their rate of annual increase in MO; and (ii) no unforeseen changes occur in cancer incidence. Unfortunately, minimal information is available for Eastern Europe. Our data call for the prospective surveillance of the cancer burden and MO availability to ensure adequate and equal care for cancer patients throughout Europe.
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Necesidades y Demandas de Servicios de Salud/tendencias , Oncología Médica , Atención a la Salud , Europa (Continente) , Femenino , Humanos , Masculino , Oncología Médica/tendencias , Neoplasias/epidemiología , Neoplasias/terapia , Médicos/provisión & distribución , Recursos HumanosRESUMEN
BACKGROUND: This randomized phase III trial compared pathologic complete response (pCR) rates of early breast cancer (EBC) following neoadjuvant epirubicin-docetaxel (ED)±capecitabine (C), and evaluated the addition of trastuzumab in HER2-positive tumors. PATIENTS AND METHODS: Patients with invasive breast cancer (except T4d) were randomly assigned to receive six 3-weekly cycles of ED (both 75 mg/m2)±C (1000 mg/m2, twice daily, days 1-14). Patients with HER2-positive disease were further randomized to receive trastuzumab (8 mg/kg, then 6 mg/kg every 3 weeks) or not. Primary end point: pCR rate at the time of surgery. RESULTS: Five hundred thirty-six patients were randomized to ED (n=266) or EDC (n=270); 93 patients were further randomized to trastuzumab (n=44) or not (n=49). pCR rate was significantly increased with EDC (23.0% versus 15.4% ED, P=0.027), and nonsignificantly further increased with trastuzumab (38.6% EDC versus 26.5% ED, P=0.212). Rates of axillary node involvement at surgery and breast conservation were improved with EDC versus ED, but not significantly; the addition of trastuzumab had no further impact. Hormone receptor status, tumor size, grade, and C (all P≤0.035) were independent prognostic factors for pCR. Trastuzumab added to ED±C significantly increased the number of serious adverse events (35 versus 18; P=0.020), mainly due to infusion-related reactions. CONCLUSION: These findings show that the integration of C into a neoadjuvant taxane-/anthracycline-based regimen is a feasible, safe, and effective treatment option, with incorporation of trastuzumab in HER2-positive disease. CLINICAL TRIAL NUMBER: NCT00309556, www.clinicaltrials.gov.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Quimioterapia Adyuvante , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Prospectivos , Taxoides/administración & dosificación , Resultado del Tratamiento , Adulto JovenRESUMEN
Insights into tumour biology of breast cancer have led the path towards the introduction of targeted treatment approaches; still, breast cancer-related mortality remains relatively high. Efforts in the field of basic research revealed new druggable targets which now await validation within the context of clinical trials. Therefore, questions concerning the optimal design of future studies are becoming even more pertinent. Aspects such as the ideal end point, availability of predictive markers to identify the optimal cohort for drug testing, or potential mechanisms of resistance need to be resolved. An expert panel representing the academic community, the pharmaceutical industry, as well as European Regulatory Authorities met in Vienna, Austria, in November 2012, in order to discuss breast cancer biology, identification of novel biological targets and optimal drug development with the aim of treatment individualization. This article summarizes statements and perspectives provided by the meeting participants.
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Receptor ErbB-2/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/terapia , Ensayos Clínicos como Asunto , Femenino , Humanos , Terapia Molecular Dirigida , Transducción de Señal , Neoplasias de la Mama Triple Negativas/clasificación , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
BACKGROUND: This randomized phase II study investigated first-line chemotherapy plus cetuximab administered every second week in KRAS wild-type metastatic colorectal cancer. PATIENTS AND METHODS: Patients received FOLFOX4 plus either standard weekly cetuximab (arm 1) or cetuximab (500 mg/m(2)) every second week (arm 2), until disease progression or unacceptable toxicity. Primary end point was the objective response rate (ORR). Progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety were also investigated. The study was not powered to establish non-inferiority, but aimed at the estimation of treatment differences. RESULTS: Of 152 randomized eligible patients, 75 were treated in arm 1 and 77 in arm 2; ORRs [53% versus 62%, odds ratio 1.40, 95% confidence interval (CI) 0.74-2.66], PFS [median 9.5 versus 9.2 months, hazard ratio (HR) 0.92, 95% CI 0.63-1.34], OS (median 25.8 versus 23.0 months, HR 0.86, 95% CI 0.56-1.30) and DCR (87%) were comparable. HRs adjusted for baseline factors were 1.01 and 0.99 for PFS and OS, respectively. Frequencies of grade 3/4 adverse events in arms 1 versus 2 were similar: most common were neutropenia (28% versus 34%) and rash (15% versus 17%). CONCLUSIONS: Activity and safety of FOLFOX4 plus either cetuximab administered weekly or every second week were similar.
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Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cetuximab , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Genotipo , Humanos , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas p21(ras) , Resultado del TratamientoRESUMEN
BACKGROUND: The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored. METHODS: All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed. RESULTS: In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0-69) and was significantly longer than in patients with BM and ECM (6 months, range 0-104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001). CONCLUSIONS: Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.
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Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Tasa de Supervivencia , SobrevivientesRESUMEN
BACKGROUND: Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit. METHODS: Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy. RESULTS: Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012). INTERPRETATION: This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ≥70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/antagonistas & inhibidores , Análisis de Supervivencia , Adulto , Anciano , Neoplasias de la Mama/patología , Femenino , Humanos , Estado de Ejecución de Karnofsky , Persona de Mediana Edad , TrastuzumabRESUMEN
BACKGROUND: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. METHODS: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34-16.66) compared with 18 months (95% CI: 14.46-21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71-44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). CONCLUSION: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes.
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Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/epidemiología , Receptor ErbB-2/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Austria/epidemiología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Estadificación de Neoplasias , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios RetrospectivosRESUMEN
Triple-negative breast cancer (TNBC) is an aggressive histological subtype with limited treatment options and very poor prognosis following progression after standard chemotherapeutic regimens. Resistance to current standard therapies such as anthracyclines or taxanes limits the available options for previously treated patients with metastatic TNBC to a small number of non-cross-resistant regimens, and there is currently no preferred standard chemotherapy. Duration of response is usually short, with rapid relapse very common and median survival of just 13 months. The newly approved agent eribulin has shown a survival benefit in patients who had previously been treated with anthracycline- or taxane-containing regimens, including in patients with TNBC. Platinum-based regimens are an emerging option for patients with BRCA1 mutation, and newer targeted agents such as anti-angiogenic treatment with bevacizumab or anti-epidermal growth factor receptor treatment with cetuximab, have shown some benefit in combination therapy. However, there remains an urgent unmet need for improved targeted agents for this patient population. Improved treatment may be facilitated by biomarker-led understanding of subgroup molecular targets, which may predict benefit from currently approved agents, as well as newer targeted drugs.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Metástasis de la Neoplasia/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Proteína BRCA1/genética , Biomarcadores de Tumor , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Resistencia a Antineoplásicos , Receptores ErbB/antagonistas & inhibidores , Femenino , Humanos , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Resultado del TratamientoRESUMEN
The current third consensus on the systemic treatment of non-small-cell lung cancer (NSCLC) builds upon and updates similar publications on the subject by the Central European Cooperative Oncology Group (CECOG), which has published such consensus statements in the years 2002 and 2005 (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137). The principle of all CECOG consensus is such that evidence-based recommendations for state-of-the-art treatment are given upon which all participants and authors of the manuscript have to agree (Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). This is of particular importance in diseases in which treatment options depend on very particular clinical and biologic variables (Zielinski CC, Beinert T, Crawford J et al. Consensus on medical treatment of non-small-cell lung cancer--update 2004. Lung Cancer 2005; 50: 129-137; Beslija S, Bonneterre J, Burstein HJ et al. Third consensus on medical treatment of metastatic breast cancer. Ann Oncol 2009; 20 (11): 1771-1785). Since the publication of the last CECOG consensus on the medical treatment of NSCLC, a series of diagnostic tools for the characterization of biomarkers for personalized therapy for NSCLC as well as therapeutic options including adjuvant treatment, targeted therapy, and maintenance treatment have emerged and strongly influenced the field. Thus, the present third consensus was generated that not only readdresses previous disease-related issues but also expands toward recent developments in the management of NSCLC. It is the aim of the present consensus to summarize minimal quality-oriented requirements for individual patients with NSCLC in its various stages based upon levels of evidence in the light of a rapidly expanding array of individual therapeutic options.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/cirugía , Guías de Práctica Clínica como Asunto , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Oncología Médica/legislación & jurisprudencia , Oncología Médica/organización & administración , Oncología Médica/tendencias , Terapia Neoadyuvante , Literatura de Revisión como Asunto , Sociedades Médicas/legislación & jurisprudenciaRESUMEN
Bortezomib-dexamethasone (Btz/Dex) is an active regimen in patients with multiple myeloma and has been used in few patients with amyloidosis. Here, we report a retrospective evaluation of the efficacy and toxicity of Btz/Dex in 26 patients with AL amyloidosis (AL). Eighteen patients (69%) received Btz/Dex as first-line treatment. Organs most frequently involved were kidneys (100%) and heart (35%); five patients (19%) had less than two organs involved. The overall response rate was 54% (14 of 26 patients), with eight patients (31%) achieving a hematologic complete remission (CR). All patients who reached a CR received Btz/Dex as first-line therapy. Median time to response was 7.5 weeks. Improvement in organ function was noticed in three patients (12%). Median progression-free survival (PFS) and overall survival (OS) was 5.0 and 18.7 months, respectively; in CR patients, however, median PFS and OS have not yet been reached. Toxicities were manageable, with hematological side effects being most common. No grade 3/4 neuropathy was observed. Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis and suggest that patients achieving a CR have a marked benefit for survival.
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Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Pirazinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Amiloidosis/tratamiento farmacológico , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/efectos adversos , Bortezomib , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas , Masculino , Persona de Mediana Edad , Pirazinas/efectos adversos , Inducción de Remisión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Patients with metastatic central nervous system (mCNS) disease progression from breast cancer have a poor prognosis and often develop associated neurological complications. Human epidermal growth factor receptor 2 (HER2)-positivity status increases the risk of developing mCNS disease. Trastuzumab is an mAb that targets HER2 and is known to extend survival across all stages of HER2-positive breast cancer. DESIGN: This review considers evidence from preclinical and clinical studies examining the value of continuing trastuzumab treatment in patients who develop mCNS disease. A wealth of data from clinical studies showed that trastuzumab prolonged survival in patients with mCNS disease, compared with no trastuzumab treatment, by effectively controlling their non-CNS disease. Trastuzumab has also been shown to penetrate an impaired blood-brain barrier to a limited degree, such as during radiotherapy, and intrathecal delivery of trastuzumab to the central nervous system (CNS) has shown promise. Research efforts are focussing on improving the delivery of trastuzumab to the CNS. CONCLUSION: Evidence indicates that patients with mCNS disease from HER2-positive breast cancer should continue to receive trastuzumab to control HER2-positive metastases outside the CNS and receive established therapies to control the mCNS disease.
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Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias del Sistema Nervioso Central/metabolismo , Neoplasias del Sistema Nervioso Central/secundario , Femenino , Humanos , Pronóstico , Receptor ErbB-2/metabolismo , TrastuzumabRESUMEN
We have previously shown in mice that vaccination with three Her-2-peptides representing B-cell epitopes of the extracellular domain of Her-2/neu induces Her-2/neu-specific IgG antibodies with strong anti-tumor activity in vitro and in vivo. We have now finalized a phase I clinical trial with an anti-Her-2/neu vaccine-construct of immunopotentiating reconstituted influenza virosomes with the three peptides in patients with metastatic breast cancer (MBC). Ten MBC patients with low protein overexpression of Her-2/neu of MBC (+ or ++ upon immunohistochemistry, FISH negative) and positive hormone receptor status were enrolled in a single center phase I study. The virosomal formulated vaccine, consisting of 10 microg/peptide, was intramuscularly applied three times on days 1, 28, and 56. The primary endpoint of the study, which lasted 12 weeks, was safety, the secondary endpoint immunogenicity. Local erythema at the injection site was the only vaccine-related side effect occurring in four patients. In 8 of 10 patients an increase in peptide-specific antibody titer measured by ELISA was found. Importantly, the induced antibodies were also directed against the native Her-2/neu protein. Cellular immune responses, as measured by in vitro production of IL-2, IFN-c, and TNF-a of PBMCs showed a marked increase after vaccination in the majority of vaccinees. Notably, the number of CD4+CD25+Foxp3+T regulatory cells, which were significantly increased compared to healthy controls prior to vaccination, was markedly reduced following vaccination. In all, the immunological responses after vaccination indicated that the patients in stage IV of disease were immunocompetent and susceptible to vaccination. The Her-2/neu multipeptide vaccine was safe, well tolerated and effective in overcoming immunological tolerance to Her-2/neu. The induction of anti-Her-2-specific antibodies could result in clinical benefit comparable to passive anti-Her-2 antibody therapy.
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Anticuerpos Antineoplásicos/inmunología , Neoplasias de la Mama/terapia , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico , Receptor ErbB-2/inmunología , Anciano , Anciano de 80 o más Años , Anticuerpos Antineoplásicos/sangre , Antígenos de Neoplasias/inmunología , Subgrupos de Linfocitos B/inmunología , Western Blotting , Separación Celular , Ensayo de Inmunoadsorción Enzimática , Epítopos de Linfocito B/inmunología , Femenino , Citometría de Flujo , Humanos , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/uso terapéutico , Vacunas de Virosoma/inmunología , Vacunas de Virosoma/uso terapéuticoRESUMEN
BACKGROUND: Treatment options for patients with metastatic breast cancer (MBC) include a rapidly expanding repertoire of medical, surgical and supportive care measures. DESIGN: To provide timely and evidence-based recommendations for the diagnostic workup and treatment of patients with MBC, an international expert panel reviewed and discussed the evidence available from clinical trials regarding diagnostic, therapeutic and supportive measures with emphasis on their impact on the quality of life and overall survival of patients with MBC. RESULTS: Evidence-based recommendations for the diagnostic workup, endocrine therapy, chemotherapy, use of targeted therapies and bisphosphonates, surgical treatment and supportive care measures in the management of patients with MBC were formulated. CONCLUSIONS: The present consensus manuscript updates evidence-based recommendations for state-of-the-art treatment of MBC depending on disease-associated and biological variables.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Ensayos Clínicos como Asunto , Medicina Basada en la Evidencia , Femenino , Humanos , Mastectomía , Metaanálisis como Asunto , PronósticoRESUMEN
BACKGROUND: In a variety of malignant diseases, molecular targeting represents a therapeutic option, whereby, when compared with chemotherapy, fewer side effects are thought to be expected. Especially in renal cell cancer (RCC), tyrosine kinase-inhibitors have been established as useful and highly effective therapy. However, tyrosine kinase-inhibitors currently approved for RCC treatment lack single molecule specificity and bear a variety of side effects of the gastro-intestinal tract, skin, heart and haematopoietic system. Therefore, the identification of novel cell surface markers is sought, which might lead to novel diagnostic and therapeutic strategies in cancer. MATERIAL AND METHODS: Paraffin-embedded RCCs from a well characterized tissue bank were immunohistochemically quantified for embryonic transmembrane antigen CD98hc (SLC3A2) expression and semi-quantitative analyses were correlated with subtype or grade of differentiation. RESULTS: We found increased CD98hc expression in different types of malign RCCs, among them clear cell (cc)RCC, papillary (p)RCC and chromophobe (ch)RCC, but lack of expression in the benign renal oncocytoma. Thereby, the extent of CD98hc expression directly complies with grade of malignancy. Furthermore, the more malignant type II pRCC significantly higher expressed CD98hc than the less malignant and more differentiated type I pRCC (type II 83.34%, type I 4.76% CD98hc positive, P < 0.00001; n = 51). The established marker for type I pRCC, Cytokreatin 7, showed 95.24% expression in type I and 26.67% expression in type II pRCC (P < 0.00001, n = 51). CONCLUSIONS: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In pRCCs, CD98hc might represent a novel and reliable marker for type II pRCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/diagnóstico , Cadena Pesada de la Proteína-1 Reguladora de Fusión/metabolismo , Neoplasias Renales/diagnóstico , Western Blotting , Citometría de Flujo , Humanos , Estadística como AsuntoRESUMEN
The serum cytokine levels (in particular interleukine-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha)) of 61 advanced stage cancer patients receiving palliative chemotherapy as outpatients were determined with quantikine immunoassays. The values were correlated with body mass index (BMI), weight loss and appetite. Furthermore cytokine levels of patients who have died within one year were compared with those of patients who have survived more than a year. Serum levels of IL-6 (median: 1.93 pg/ml, range: 0.32-42.87) and of TNF-alpha (median: 2.55 pg/ml, range: 1.03-34.06) did not correlate with BMI, weight loss and appetite. Serum IL-6 levels of patients with survival time less than one year were significantly higher than the levels of patients who survived more than one year, no significant differences in TNF-alpha serum levels were evident. The data of this observation are consistent with current literature. Due to changes in serum levels of proinflammatory cytokines in response to chemotherapy and additional therapy, it is unlikely that IL-6 and TNF-alpha can be used as independent indicators for weight loss and appetite. Nevertheless, high serum levels of IL-6 correlate with short-time mortality.
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Antineoplásicos/uso terapéutico , Índice de Masa Corporal , Interleucina-6/sangre , Neoplasias/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/sangre , Adulto , Anciano , Atención Ambulatoria/métodos , Apetito , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/mortalidad , Cuidados Paliativos , Tasa de Supervivencia , Pérdida de PesoRESUMEN
Symptomatic brain metastases (BM) are a frequent and late complication in cancer patients. However, a subgroup of cancer patients presents with BM as the first symptom of metastatic cancer. Here we aimed to analyze the clinical course and prognostic factors of this particular BM patient population. Patients presenting with newly diagnosed BM without a history of metastatic cancer were identified from the Vienna Brain Metastasis Registry. Clinical characteristics and overall survival were retrieved by chart review. 459/2419 (19.0%) BM patients presented with BM as first symptom of advanced cancer. In 374/459 (81.5%) patients, an extracranial primary tumor, most commonly lung cancer, could be identified within 3 months after BM diagnosis. In 85/459 (18.5%) patients no extracranial primary tumor could be identified despite comprehensive diagnostic workup within the first 3 months after diagnosis of BM. Survival of patients with identified extracranial tumor differed only numerically from patients with cancer of unknown primary (CUP), however patients receiving targeted therapy after molecular workup showed significantly enhanced survival (20 months vs. 7 months; p = 0.003; log rank test). The GPA score showed a statistically significant association with median overall survival times in the CUP BM patients (class I: 46 months; class II: 7 months; class III: 4 months; class IV: 2 months; p < 0.001; log rank test). The GPA score has a strong prognostic value in patients with CUP BM and may be useful for patient stratification in the clinical setting. Comprehensive diagnostic workup including advanced imaging techniques and molecular tissue analyses appears to benefit patients by directing specific molecular targeted therapies.