RESUMEN
BACKGROUND: Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug. METHODS: In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB-IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0-2. Patients were randomly assigned (1:1) to receive a carboplatin-based doublet intravenously (carboplatin area under the concentration curve [AUC] 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days; carboplatin AUC 4 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days; or carboplatin AUC 5 on day 1 plus pegylated liposomal doxorubicin 30 mg/m2 on day 1, every 28 days), or a carboplatin-based doublet plus bevacizumab (10 mg/kg intravenous every 14 days combined with pegylated liposomal doxorubicin-carboplatin, or 15 mg/kg every 21 days combined with gemcitabine-carboplatin or paclitaxel-carboplatin). Evaluable disease according to RECIST 1.1 guidelines was required before randomisation. Randomisation was done through the trial website with a minimisation procedure, stratified by centre, time of recurrence, performance status, and type of second-line chemotherapy. The primary endpoint was investigator-assessed progression-free survival, analysed on an intention-to-treat basis. Safety was assessed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov, NCT01802749 and EudraCT 2012-004362-17. FINDINGS: Between Dec 6, 2013, and Nov 11, 2016, 406 patients were recruited (203 [50%] assigned to the bevacizumab group and 203 [50%] to the standard chemotherapy group). 130 patients (64%) in the bevacizumab group and 131 (65%) in the standard chemotherapy group had progressed after receiving a last dose of platinum more than 12 months before, and 146 patients (72%) in the bevacizumab group and 147 (72%) in the standard chemotherapy group had progressed after completion of first-line bevacizumab maintenance. 161 participants (79%) progressed in the standard chemotherapy group, as did 143 (70%) in the bevacizumab group. Median progression-free survival was 8·8 months (95% CI 8·4-9·3) in the standard chemotherapy group and 11·8 months (10·8-12·9) in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41-0·65; log-rank p<0·0001). Most common grade 3-4 adverse events were hypertension (20 [10%] in the standard chemotherapy group vs 58 (29%) in the bevacizumab group), neutrophil count decrease (81 [41%] vs 80 [40%]), and platelet count decrease (43 [22%] vs 61 [30%]). 68 patients (33%) died in the standard chemotherapy group and 79 (39%) died in the bevacizumab group; two deaths (1%) in the standard chemotherapy group and one death (<1%) in the bevacizumab group were deemed to be treatment-related. INTERPRETATION: Continuing bevacizumab beyond progression combined with chemotherapy in patients with platinum-sensitive recurrent ovarian cancer improves progression-free survival compared with standard chemotherapy alone and might be considered in clinical practice. FUNDING: Hoffmann-La Roche and Associazione Italiana per la Ricerca sul Cancro.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Carboplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Carboplatino/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Polietilenglicoles/administración & dosificaciónRESUMEN
Importance: The COVID-19 pandemic has been associated with substantial reduction in screening, case identification, and hospital referrals among patients with cancer. However, no study has quantitatively examined the implications of this correlation for cancer patient management. Objective: To evaluate the association of the COVID-19 pandemic lockdown with the tumor burden of patients who were diagnosed with metastatic colorectal cancer (mCRC) before vs after lockdown. Design, Setting, and Participants: This cohort study analyzed participants in the screening procedure of the PANIRINOX (Phase II Randomized Study Comparing FOLFIRINOX + Panitumumab vs FOLFOX + Panitumumab in Metastatic Colorectal Cancer Patients Stratified by RAS Status from Circulating DNA Analysis) phase 2 randomized clinical trial. These newly diagnosed patients received care at 1 of 18 different clinical centers in France and were recruited before or after the lockdown was enacted in France in the spring of 2020. Patients underwent a blood-sampling screening procedure to identify their RAS and BRAF tumor status. Exposures: mCRC. Main Outcomes and Measures: Circulating tumor DNA (ctDNA) analysis was used to identify RAS and BRAF status. Tumor burden was evaluated by the total plasma ctDNA concentration. The median ctDNA concentration was compared in patients who underwent screening before (November 11, 2019, to March 9, 2020) vs after (May 14 to September 3, 2020) lockdown and in patients who were included from the start of the PANIRINOX study. Results: A total of 80 patients were included, of whom 40 underwent screening before and 40 others underwent screening after the first COVID-19 lockdown in France. These patients included 48 men (60.0%) and 32 women (40.0%) and had a median (range) age of 62 (37-77) years. The median ctDNA concentration was statistically higher in patients who were newly diagnosed after lockdown compared with those who were diagnosed before lockdown (119.2 ng/mL vs 17.3 ng/mL; P < .001). Patients with mCRC and high ctDNA concentration had lower median survival compared with those with lower concentration (14.7 [95% CI, 8.8-18.0] months vs 20.0 [95% CI, 14.1-32.0] months). This finding points to the potential adverse consequences of the COVID-19 pandemic and related lockdown. Conclusions and Relevance: This cohort study found that tumor burden differed between patients who received an mCRC diagnosis before vs after the first COVID-19 lockdown in France. The findings of this study suggest that CRC is a major area for intervention to minimize pandemic-associated delays in screening, diagnosis, and treatment.
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Neoplasias Colorrectales/patología , Control de Enfermedades Transmisibles/organización & administración , Aceptación de la Atención de Salud , Carga Tumoral , Adulto , Anciano , Biomarcadores de Tumor/genética , COVID-19/epidemiología , ADN Tumoral Circulante/sangre , Ensayos Clínicos Fase II como Asunto , Estudios de Cohortes , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Estudios Controlados Antes y Después , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Ensayos Clínicos Controlados Aleatorios como Asunto , SARS-CoV-2RESUMEN
BACKGROUND: Intraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats. METHODS: To determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37 degrees C. RESULTS: No deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure. CONCLUSION: The combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine.
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Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino/uso terapéutico , Epinefrina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Cisplatino/efectos adversos , Epinefrina/efectos adversos , Epinefrina/toxicidad , Femenino , Francia , Lesiones Cardíacas/inducido químicamente , Humanos , Inyecciones Intraperitoneales , Cuidados Intraoperatorios , Persona de Mediana Edad , Neoplasias Ováricas/cirugía , Resultado del TratamientoRESUMEN
PURPOSE: Genomic tests can identify ER-positive HER2-negative localized breast cancer patients who may not benefit from adjuvant chemotherapy. Such tests seem especially interesting in "intermediate" clinico-pathological risk categories. The psychological impact of the decision uncertainty in these women remains largely unexplored. We assessed the clinical and psychological impact of EndoPredict® (EpClin), a clinico-genomic test, in these patients. METHODS: This multicenter, single arm prospective study (NCT02773004) enrolled patients for which adjuvant chemotherapy was uncertain, based on predefined criteria. The primary endpoint was the proportion of change between initial adjuvant decision and final administration of chemotherapy. Secondary endpoints included post-test (Day 17) and 1-year patient reported outcomes. RESULTS: One third of 200 evaluable patients had a high EpClin score (≥3.32867; 10 years cumulative risk of distance failure ≥10%). The overall change rate of chemotherapy decision was 72/200 (35.8%, 95% CI 29.2-42.4). Chemotherapy was withdrawn in 57 cases (28.4% [22.2-34.8]) and added in 15 (7.5% [3.8-11.2]. 6 changes (8%) were based on patients' decisions. Anxiety and distress levels increased at Day 17 when adding chemotherapy after the test result (p < 10-7 and 0.00022 respectively), while stable in other situations. At 1-year, all patients had returned to the baseline anxiety and distress levels (mean anxiety 51.5, +/- SD = 2.5 [max. 80], mean distress 3±1 [max. 10]). CONCLUSIONS: EndoPredict ® (EpClin) is clinically useful in deciding whether or not to administer adjuvant chemotherapy in patients with intermediate risk. A single-step decision is preferable since adding chemotherapy at a later stage increases anxiety and distress.
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Neoplasias de la Mama/tratamiento farmacológico , Reglas de Decisión Clínica , Toma de Decisiones Clínicas/métodos , Genes erbB-2 , Pruebas Genéticas/métodos , Receptores de Estrógenos/genética , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Ansiedad/diagnóstico , Ansiedad/etiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Femenino , Marcadores Genéticos , Genómica , Humanos , Mastectomía , Persona de Mediana Edad , Medición de Resultados Informados por el Paciente , Estudios Prospectivos , Distrés Psicológico , Medición de Riesgo , IncertidumbreRESUMEN
BACKGROUND: Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHODS: Thirty-one patients with advanced epithelial cancer classified as International Federation of Gynecology and Obstetrics stage IIIC were included in the study. Blood and IP samples were taken over a 24-hour period during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentrations were analysed using a population approach with nonlinear mixed-effects modelling (NONMEM) software. Improvement of the model with covariates was performed as well as assessment of the model using bootstrap and posterior visual predictive methods. RESULTS: Both IP fluid and serum pharmacokinetics were satisfactorily described with a three-compartment model for both Uf Pt and total Pt concentrations. The covariates were bodyweight for the IP volume of distribution in the Uf Pt model, and both IP and serum protein concentrations for the clearance from the central compartment in the total Pt model. A nomogram, based on the results of the Monte Carlo simulations, displays a dose recommendation regarding both the risk of renal toxicity and the potent efficacy of the treatment. A limited sampling strategy (LSS) allowing the estimation of potential risk of renal toxicity is also described. CONCLUSION: The pharmacokinetics of cisplatin during peroperative IP chemotherapy could be successfully fitted with the present model, which allowed a dosing strategy accompanied by an LSS to facilitate the follow-up of patients.
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Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Cisplatino/farmacocinética , Cisplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Adulto , Anciano , Antineoplásicos/farmacología , Área Bajo la Curva , Cisplatino/farmacología , Terapia Combinada , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Inyecciones Intraperitoneales , Periodo Intraoperatorio , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Biológicos , Método de Montecarlo , Dinámicas no Lineales , Neoplasias Ováricas/metabolismo , Medición de RiesgoRESUMEN
BACKGROUND: Intra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer. METHODS: From January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours. RESULTS: Median age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment. CONCLUSION: This study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cuidados Intraoperatorios , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/secundario , Carcinoma Endometrioide/cirugía , Quimioterapia del Cáncer por Perfusión Regional , Cisplatino/administración & dosificación , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/secundario , Cistadenocarcinoma Seroso/cirugía , Estudios de Factibilidad , Femenino , Humanos , Inyecciones Intraperitoneales , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/cirugía , Pronóstico , Resultado del TratamientoRESUMEN
Ovarian cancer is the leading cause of gynecological cancer-related death in Western countries. The present treatment standards for ovarian cancer are based on the association of debulking surgery with platinum-based chemotherapy. Another strategy that could be further investigated is intraperitoneal chemotherapy (IP). We previously described that the 2-h administration of intraoperative IP cisplatin did not reach satisfactory concentrations. In the present study, we present the results of a pharmacokinetic analysis performed after two consecutive 1-h IP 30 mg/l cisplatin administrations. Twenty-seven patients with advanced epithelial cancer classified FIGO stage IIIC were included in the study. Blood and IP samples were taken over a 24-h period, during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentration levels were analyzed. Biological and clinical toxicities were also recorded. With this strategy, IP Pt concentrations stayed above the target concentration (10 mg/l) for a satisfactory length of time. The serum Pt concentrations were higher than those observed with the "one-bath" protocol and they induced the occurrence of recoverable renal toxicities (3 grade 1, 7 grade 2 and 4 grade 3). The best predictive parameter for renal failure was the total Pt 24-h Area Under the Curve (AUC) with a threshold value of 25 mg h/l RR = 0.31 (95% CI 0.13 - 0.49, P < 0.01). Administration of an increased amount of cisplatin is feasible and a satisfactory level of IP Pt concentrations is obtained. However, this improvement is associated with an increase in serum Pt levels and resulting renal toxicities. An attractive solution would be to decrease Pt transfer from peritoneum to bloodstream. A phase 1 study using intraoperative IP epinephrine in order to decrease this transfer is presently being carried out.
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Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Cisplatino/farmacocinética , Cisplatino/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/uso terapéutico , Área Bajo la Curva , Carboplatino/uso terapéutico , Cisplatino/administración & dosificación , Femenino , Humanos , Infusiones Parenterales , Periodo Intraoperatorio , Persona de Mediana Edad , Estadificación de Neoplasias , Paclitaxel/uso terapéutico , Unión ProteicaRESUMEN
PURPOSE OF REVIEW: The use of tobacco and/or alcohol is linked with the occurrence of head and neck squamous cell carcinoma, esophagus cancer and lung cancer. If these carcinogenic factors can induce the development of a cancer in one of these locations, it would seem reasonable that a second cancer could appear in another of those areas, at the same time or at some point in the future. RECENT DEVELOPMENTS: This is the reason why one can consider that triple endoscopy is required as the optimal evaluation in patients with head and neck cancer. Nevertheless, the usefulness of this systematic procedure, which includes nasopharyngoscopy, laryngoscopy, pharyngoscopy, bronchoscopy and esophagoscopy, is debatable. The low number of head and neck cancers associated with synchronous primary cancers in the esophagus and/or lungs reported by several studies does not support this procedure and its morbidity. In contrast, in other studies a higher rate was observed and the authors pointed out the impact of such findings on treatment strategy, suggesting the benefit of routine triple endoscopy. One can conclude that the relevance of routine triple endoscopy is related to the rate of second synchronous primary cancer detected. A search to identify predictive factors of synchronous cancer occurrence will therefore be required. SUMMARY: This review summarizes the available data in the literature and highlights the need for selected patients with head and neck cancer to receive triple endoscopy.
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Carcinoma de Células Escamosas/patología , Endoscopía/métodos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de los Bronquios/patología , Broncoscopía , Esofagoscopía , Humanos , Laringoscopía , Neoplasias Pulmonares/patología , Metástasis de la Neoplasia , Estadificación de Neoplasias/métodos , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Secundarias/patologíaRESUMEN
The aim of this study was to analyse prognostic factors for disease free interval (DFI) and overall survival (OS) among patients with larynx and hypopharynx cancer requiring a total laryngectomy. Three groups of patients were studied according to the type of treatment they received. Fifty-eight patients had total laryngectomy, 71 patients had organ preservation treatment including induction chemotherapy followed by exclusive radiotherapy, 26 patients received induction chemotherapy followed by salvage total laryngectomy. The studied potential prognostic factors were age, gender, performans status, primary tumor localization, T status, N status, tumor volume and tumoral EGFR level (fmol/mg protein). The multivariate analysis showed that both N status and tumor volume were significant for DFI and OS. EGFR level was significant only for patients treated by induction chemotherapy and exclusive radiotherapy (p = 0.05 and 0.05 for DFI and OS length, respectively). Among this group, patients with tumor EGFR levels lower and higher than 100 fmol/mg protein had 53% versus 22% and 51% versus 18% 5-year of DFI and OS rates, respectively (Log rank test: p = 0.001 and 0.0001). EGFR determination appears to be a powerful prognostic parameter for patients treated by induction chemotherapy followed by exclusive radiotherapy. Laryngectomy seems to erase the prognostic impact of EGFR expression. These results profile the use of EGFR targeting therapy for this category of patients.
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Biomarcadores de Tumor/análisis , Receptores ErbB/análisis , Neoplasias Hipofaríngeas/química , Neoplasias Laríngeas/química , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Hipofaríngeas/tratamiento farmacológico , Neoplasias Hipofaríngeas/cirugía , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/cirugía , Laringectomía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The aim of this study was to evaluate the objective tumor response rates and toxicities in elderly patients (older than 70 years) with advanced colorectal cancer treated with 5-fluorouracil (5-FU) as a first-line palliative chemotherapy regimen. Eighty-six consecutive patients were enrolled onto a retrospective study between January 1990 and February 1998. Patients were divided into two groups; group 1 consisted of patients who were 70 to 74 years old, and group 2 consisted of patients who were age 75 years and older. Four types of 5-FU-based chemotherapy were administered. First-line chemotherapy was continued until disease progression, unacceptable toxicity, or patient refusal. Primary tumor sites were the colon (n = 44), rectum (n = 29), and colorectal (n = 13). There was no difference in response (complete/partial) rates according to age groups (group 1: 21%, group 2: 26%). Median overall survival was 17 months for group 1 and 14 months for group 2, with 1-year survival at 63% and 55%, respectively (not statistically significant). Median time to progression was 6 months for both age groups. Chemotherapy in both groups increased performance status, and weight in 26% and 31%, respectively. No toxic death was reported. There was no difference in overall or severe toxicity between the two age groups, and all adverse events were manageable. Toxicity (grade III/IV) occurred in 25% of patients. Based on these findings, palliative first-line chemotherapy for colorectal cancer can be performed in selected elderly patients without increasing either morbidity or mortality, while obtaining response rates and side effects comparable to those in younger patients.
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Antimetabolitos Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/uso terapéutico , Cuidados Paliativos , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Neoplasias Colorrectales/patología , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Masculino , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Chemotherapy has emerged to be a central component of curative strategies for patient with primary squamous cell carcinoma of the head and neck. The identification of agent active in head and neck cancer first occurred in patients with local regional recurrent and/or metastatic disease treated with palliative intent. The present paper reports the prognostic factors which based the understanding of these patients outcome. A review of the relevant results obtained by the standard chemotherapy in this recurrent population is performed. The current and future area of research were highlighted.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Receptores ErbB/antagonistas & inhibidores , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Sistema Respiratorio/tratamiento farmacológico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Cetuximab , Expresión Génica , Genes p53/fisiología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Humanos , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias del Sistema Respiratorio/genética , Neoplasias del Sistema Respiratorio/patologíaRESUMEN
Anaemia is one of the most dreaded complications among patients with malignant pathologies. Its causes can be varied and whatever its severity, the impact on the quality of life of the patient remains essential. However, the epidemiologic data concerning anaemia are very few in the literature. This is why we carried out a large national survey about the prevalence and the management of anaemia among patients with malignant diseases. The F-ACT (French Anaemia Cancer Treatment) study is a retrospective observational multicentric study conducted with 178 experts practicing in 112 centers or units treating patients with solid tumours and/or malignant haematological diseases. Control over one day standard of consultation for each questioned expert, 2 782 patients were enrolled, including 1 892 (68%) patient with solid tumour and 890 (27%) patient with malignant haematological disease. The median age was 61 years (range : 18-93 years) including 1 335 women (48%) and 1 447 men (52%). A the date of enrollment, the median level of haemoglobin (Hb) was 11,6 g/dl (range: 5,2-18,5 g/dl) and 44% of patient had a level of Hb < 11 g/dl. An anaemia was found in all the cancer localizations and whatever the stage or the therapeutic status of the disease. Approximately 2/3 of the anaemic patients received treatment by erythropoiesis stimulating agent (ESA) and approximately 17% of them did not receive any specific treatment for this anaemia. The median level of Hb at the introduction of the ESA was 10 g/dl. These results, compared with those reported in study ECAS (European Cancer Anaemia Survey) in 2001, seem to show an improvement in the management of anaemia and the use of the ESA, in particular an earlier introduction of this type of treatment since the appearance of anaemia.
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Anemia/terapia , Neoplasias/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia/epidemiología , Anemia/etiología , Transfusión Sanguínea/estadística & datos numéricos , Eritropoyesis , Femenino , Francia/epidemiología , Encuestas de Atención de la Salud , Hematínicos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Hemoglobina A/análisis , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/patología , Prevalencia , Estudios RetrospectivosRESUMEN
Neoadjuvant chemotherapies for patients with advanced head and neck squamous cell carcinoma have been widely studied for twenty years. Despite a high level of activity on the primary tumor, no study has demonstrated a survival benefit suggesting the use of neoadjvant chemotherapy. One can consider that the only benefit of such strategy is for larynx preservation in patients with operable hypopharnx or larynx cancer. Nevertheless, recently the well established preservation strategy based on induction chemotherapy following according to the activity by radiotherapy has been knocked over by a strategy developed by Forastiere et al. using primary concomitant chemoradiotherapy. However, the lack of benefit reported by neoadjuvant chemotherapy has been thwarted by the recent results provided by the EORTC study which assessed the survival benefit of neoadjuvant chemotherapy by docetaxel-cisplatin-fluorouracile. Interestingly, since 2002 the clearly established strategies for patients with advanced head and neck cancer have been challenged and new options are emerging. This paper reviews the standard strategy of the past and the future proposal emerging from recent studies.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas/cirugía , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Neoplasias Laríngeas/tratamiento farmacológico , Neoplasias Laríngeas/cirugía , Neoplasias Faríngeas/tratamiento farmacológico , Neoplasias Faríngeas/cirugía , Inducción de RemisiónRESUMEN
INTRODUCTION: Anaemia is a common toxicity in cancer patients and epoetins (EPOs) are now an established treatment. The economic profile of EPO treatment was assessed in patients with breast cancer treated by adjuvant-chemotherapy. MATERIALS AND METHODS: Two strategies were compared: without treatment by EPO and with the possible use of treatment by EPO (epoetin alfa) when required. The clinical effectiveness criterion was time adjusted to quality of life and economic data included only direct medical costs. MAIN RESULTS: One hundred ninety-two patients were included. In the group with the strategy containing the possible use of EPO, 45.5% of patients effectively received EPO. A significant difference in the haemoglobin level profile over time was observed which provided a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year (QALY) associated with an extra cost of
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Anemia/tratamiento farmacológico , Anemia/economía , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/economía , Eritropoyetina/economía , Eritropoyetina/uso terapéutico , Adulto , Anciano , Anemia/inducido químicamente , Biomarcadores/sangre , Quimioterapia Adyuvante , Análisis Costo-Beneficio , Ciclofosfamida/efectos adversos , Doxorrubicina/efectos adversos , Epirrubicina/efectos adversos , Epoetina alfa , Femenino , Fluorouracilo/efectos adversos , Francia , Hematínicos/economía , Hematínicos/uso terapéutico , Hemoglobinas/efectos de los fármacos , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Proteínas Recombinantes , Estudios Retrospectivos , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
Intraperitoneal (i.p.) chemotherapy is a promising therapeutic method to improve the effectiveness of cisplatin in patients with ovarian cancer and peritoneum involvement. Intraperitoneal treatment can be intraoperatively performed just after a complete surgical resection of peritoneal tumor nodules. However, little is known regarding the pharmacokinetics of platinum during intraoperative i.p. chemotherapy (IIC). Serum and i.p. measurements of total and ultrafilterable platinum were performed to determined pharmacokinetic parameters in 11 consecutive patients who received a 2-h IIC with 50 mg/m cisplatin. Protein concentrations were determined in serum and peritoneal liquid at the same times. The cisplatin concentration required to kill OVCAR-3 human ovarian cancer cells and evaluation of cisplatin binding to proteins were determined in vitro. Platinum i.p. concentration decreased rapidly and quickly came under the cytotoxicity threshold (10 mg for 2 h). About 85% of i.p. and serum cisplatin was ultrafilterable during IIC. Platinum concentrations were closely related to protein concentrations. Due to the very low level of serum protein (almost 25 g/l), serum cisplatin binding during chemotherapy was very low (almost 25%), but increased with protein concentration recovery. These pharmacokinetic data show that a sufficient concentration to kill human ovarian cancer is not reached with a single i.p. bath containing 50 mg/m cisplatin for 2 h. A new protocol with a renewed bath and a higher cisplatin concentration is under investigation.
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Cisplatino/farmacocinética , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Antineoplásicos/farmacocinética , Antineoplásicos/farmacología , Área Bajo la Curva , Líquido Ascítico/metabolismo , Proteínas Sanguíneas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cisplatino/sangre , Cisplatino/metabolismo , Terapia Combinada , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Infusiones Parenterales , Periodo Intraoperatorio , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/cirugía , Unión Proteica/efectos de los fármacosRESUMEN
BACKGROUND: The objective of the current study was to analyze the results obtained by triple endoscopy during the initial evaluation of a primary carcinoma of the head and neck. METHODS: A total of 487 patients with a squamous cell carcinoma of the head and neck was studied. None of the patients had evidence of metastasis or a second primary tumor on the thoracic computed tomography (CT) scan or chest X-ray. All patients underwent a triple endoscopy including nasopharyngoscopy, laryngoscopy, pharyngoscopy, bronchoscopy, and esophagoscopy. RESULTS: A synchronous primary invasive carcinoma of the lung and esophagus was diagnosed in 5 patients (1%) and 10 patients (2%), respectively. In addition, nine lesions were considered to be a regional extension of the primary tumor to the esophagus, and nine in situ carcinomas were observed. It is interesting to note that a significant correlation was found between the risk of a second synchronous esophageal carcinoma and the initial location of the primary head and neck carcinoma (P = 0.002, chi-square test). Esophageal carcinoma was observed in 1.3% of the patients with an oropharyngeal tumor, 2% of the patients with a laryngeal tumor, none of the patients with a tumor of the oral cavity, and 9.2% of the patients with a hypopharyngeal tumor. CONCLUSIONS: The role of bronchoscopy and esophagoscopy in the presence of a normal thoracic CT scan has been questioned because of the relatively low incidence of a second esophageal and/or lung primary tumor. Nonetheless, based on the same incidence criterion, it appears reasonable to schedule a routine esophagoscopy for those patients with a squamous cell carcinoma of the hypopharynx.