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1.
Haematologica ; 96(1): 55-61, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20971817

RESUMEN

BACKGROUND: Epidemiological data on myeloid malignancies are very rare in the literature due to a lack of registration by cancer registries until 2000. The Registry of Hematologic Malignancies of the Côte d'Or Department in France has, however, steadfastly registered data on cases occurring in the Department since 1980, resulting, to date, in a database of over 5,000 cases classified according to the ICD-O-3 classification, following the most recent World Health Organization classification criteria. DESIGN AND METHODS: Twenty-five years of data on myeloid malignancies, including acute myeloid leukemia, myeloproliferative neoplasms, myelodysplastic syndromes and myelodysplastic/myeloproliferative syndromes were analyzed. World population standardized incidence rates were calculated as were as observed and relative survival. RESULTS: Incidence rates per 100,000 inhabitants/year were 2.5 for acute myeloid leukemia, 1.3 for myelodysplastic syndromes, 3.2 for myeloproliferative neoplasms and 0.6 for myelodysplastic/myeloproliferative syndromes. It was found that the incidence rate of myelodysplastic syndromes increased significantly over the period. The median overall survival is 8.9 months for patients with acute myeloid leukemia, 33.8 months for patients with myelodysplastic syndromes, 91.7 months for those with myeloproliferative neoplasms and 26.6 months for patients with myelodysplastic/myeloproliferative syndromes. Observed and relative 20-year survival rates are, respectively, 12% and 13% in acute myeloid leukemia, 2% and 6% in myelodysplastic syndromes and 20% and 34% in myeloproliferative neoplasms. CONCLUSIONS: These population-based data on myeloid malignancies are the first data collected over such a long period and provide interesting information for clinicians and public health authorities, particularly given the paucity of other long-term, population-based data from cancer registries.


Asunto(s)
Leucemia Mieloide Aguda/epidemiología , Síndromes Mielodisplásicos/epidemiología , Trastornos Mieloproliferativos/epidemiología , Adulto , Factores de Edad , Anciano , Femenino , Francia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Registros , Sistema de Registros , Factores Sexuales , Tasa de Supervivencia , Factores de Tiempo
2.
Br J Clin Pharmacol ; 69(1): 58-66, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20078613

RESUMEN

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Numerous clinical studies, including a few prospective ones, have reported conflicting results on the impact of gene polymorphisms related to fluorouracil (FU) and oxaliplatin pharmacodynamics. WHAT THIS STUDY ADDS: * This prospective study is the first to report that clinical response to FOLFOX is significantly related to methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (677C-->T and 1298A-->C), with a response rate of 37, 53, 63 and 80% in patients harbouring no, one, two or three favourable MTHFR alleles, respectively. * Only polymorphisms of genes related to oxaliplatin pharmacodynamics (GSTpi 105Ile-->Val and XPD 751Ly-->Gln) influenced progression-free survival. * These results corroborate the observation that response was related to the cumulative FU dose, whereas progression-free survival was related to the cumulative oxaliplatin dose. AIMS: To test prospectively the predictive value of germinal gene polymorphisms related to fluorouracil (FU) and oxaliplatin (Oxa) pharmacodynamics on toxicity and responsiveness of colorectal cancer (CRC) patients receiving FOLFOX therapy. METHODS: Advanced CRC patients (n= 117) receiving FOLFOX 7 therapy were enrolled. Gene polymorphisms relevant for FU [thymidylate synthase (TYMS, 28 bp repeats including the G-->C mutation + 6 bp deletion in 3'UTR), methylenetetrahydrofolate reductase (MTHFR, 677C-->T, 1298A-->C), dihydropyrimidine deshydrogenase (IVS14+1G-->A) and Oxa: glutathione S-transferase (GST) pi (105Ile-->Val, 114Ala-->Val), excision repair cross-complementing group 1 (ERCC1) (118AAT-->AAC), ERCC2 (XPD, 751Lys-->Gln) and XRCC1 (399Arg-->Gln)] were determined (blood mononuclear cells). RESULTS: None of the genotypes was predictive of toxicity. Response rate (54.7% complete response + partial response) was related to FU pharmacogenetics, with both 677C-->T (P= 0.042) and 1298A-->C (P= 0.004) MTHFR genotypes linked to clinical response. Importantly, the score of favourable MTHFR alleles (677T and 1298C) was positively linked to response, with response rates of 37.1, 53.3, 62.5 and 80.0% in patients bearing no, one, two or three favourable alleles, respectively (P= 0.040). Polymorphisms of genes related to Oxa pharmacodynamics showed an influence on progression-free survival, with a better outcome in patients bearing GSTpi 105 Val/Val genotype or XPD 751Lys-containing genotype (P= 0.054). CONCLUSIONS: These results show that response to FOLFOX therapy in CRC patients may be driven by MTHFR germinal polymorphisms.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Polimorfismo Genético , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Dihidrouracilo Deshidrogenasa (NADP)/genética , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Glutatión Transferasa/genética , Humanos , Leucovorina , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino , Estudios Prospectivos , Eliminación de Secuencia , Análisis de Supervivencia
3.
Haematologica ; 91(4): 530-3, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16537118

RESUMEN

We reviewed 64 pregnancies in 26 women with Diamond-Blackfan anemia (DBA) included in the French and German DBA registries. Complications were seen in 42 pregnancies (66%) and included abortion, pre-eclampsia, in utero fetal death, intrauterine growth retardation, retroplacental hematoma, pre-term delivery and fetal malformations. Of the 34 children (53%) born alive, 13 had DBA. No correlations were found between pregnancy outcome and features of either maternal or child DBA. Pregnancies in DBA-affected women are at high risk, especially for complications likely to be of vascular-placental origin. Careful monitoring with prevention of severe anemia and early introduction of aspirin is suggested.


Asunto(s)
Anemia de Diamond-Blackfan/complicaciones , Complicaciones del Embarazo/etiología , Anemia/prevención & control , Anemia de Diamond-Blackfan/tratamiento farmacológico , Aspirina/uso terapéutico , Recolección de Datos , Femenino , Francia , Alemania , Humanos , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/prevención & control , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Complicaciones Cardiovasculares del Embarazo/etiología , Sistema de Registros , Estudios Retrospectivos
4.
Haematologica ; 91(8): 1027-32, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16885042

RESUMEN

BACKGROUND AND OBJECTIVES: In non-randomized studies, thalidomide appeared to be effective in myeloid metaplasia with myelofibrosis (MMM). We compared thalidomide to placebo for treatment of anemia in MMM. DESIGN AND METHODS: A prospective phase II B, randomized double-blind multicenter trial comparing thalidomide 400 mg/d with placebo for 180 days was conducted in 52 anemic patients (hemoglobin pounds Sterling 9 g/dL or transfused). The main outcome measure was a 2 g/L increase in hemoglobin or 20% reduction in transfusions. RESULTS: In the thalidomide group only 10 patients completed 6 months of treatment. At 180 days, in an intention-to-treat analysis, no difference was observed between the thalidomide and placebo groups as regards improvement of hemoglobin levels (one patient in each group) or reduction of red blood cell transfusions (three vs five patients, respectively). The spleen size, determined by ultrasonography, increased significantly less in the thalidomide group than in the placebo group (p < 0.05). Thalidomide had no apparent benefit on the Dupriez score, the severity score, survival, death, or any other clinical or biological parameter. Somnolence, gastro-intestinal signs, weight gain, and edema were significantly more frequent in the thalidomide group. Outpatient discontinuation of thalidomide was significantly correlated with a high severity score > 4 (odds ratio, OR = 16; p < 0.01), and g-glutamyl transferase levels > 40 IU/L (OR = 12; p < 0.05). INTERPRETATION AND CONCLUSIONS: Thalidomide (200-400 mg/d) does not demonstrate substantial efficacy in anemic MMM patients. The natural history of disease in the placebo group revealed spontaneous periods of remission of anemia. Tolerance of thalidomide was significantly correlated wih the severity and liver involvement of the disease.


Asunto(s)
Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/tratamiento farmacológico , Talidomida/uso terapéutico , Inhibidores de la Angiogénesis/uso terapéutico , Método Doble Ciego , Francia , Humanos , Placebos , Reproducibilidad de los Resultados , Proyectos de Investigación , Talidomida/toxicidad
5.
J Clin Oncol ; 21(15): 2896-903, 2003 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-12885807

RESUMEN

PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer. PATIENTS AND METHODS: LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion. RESULTS: A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001). CONCLUSION: Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Adenocarcinoma/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioterapia Adyuvante , Distribución de Chi-Cuadrado , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Infusiones Intravenosas , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del Tratamiento
6.
Gastroenterol Clin Biol ; 28(12): 1281-3, 2004 Dec.
Artículo en Francés | MEDLINE | ID: mdl-15671939

RESUMEN

Although chemoembolization is known to be an effective palliative treatment in hepatocellular carcinoma, it has a limited effect in large tumors. We report the case of a patient with a large hepatocellular carcinoma of the left liver who had a significant and sustained clinical response after six sessions of chemoembolization with a pirarubicin/amiodarone/lipiodol emulsion. Pirarubicin is an anthracycline which penetrates faster than doxorubicin into cancer cells. Amiodarone is a multidrug resistance inhibitor. Polysorbate 80, an excipient of injectable amiodarone stabilizes the anthracycline/lipiodol emulsion. The clinical efficacy of this new formulation could be evaluated in a phase II clinical trial.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Doxorrubicina/análogos & derivados , Neoplasias Hepáticas/terapia , Amiodarona/administración & dosificación , Medios de Contraste/administración & dosificación , Doxorrubicina/administración & dosificación , Inhibidores Enzimáticos/administración & dosificación , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Intraarteriales , Aceite Yodado/administración & dosificación , Masculino , Persona de Mediana Edad , alfa-Fetoproteínas/análisis
7.
J Clin Oncol ; 27(34): 5727-33, 2009 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-19786657

RESUMEN

PURPOSE: This study compared chemotherapy discontinuation with maintenance therapy with leucovorin and fluorouracil after six cycles of folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy in the first-line treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Two hundred two patients with untreated metastatic colorectal cancer were randomly assigned to receive six cycles of modified FOLFOX7 (mFOLFOX7) followed by simplified leucovorin plus bolus and infusional fluorouracil until progression (arm 1 or maintenance arm, n = 98) or six cycles of mFOLFOX7 before a complete stop of chemotherapy (arm 2 or chemotherapy-free interval [CFI] arm, n = 104). Reintroduction of mFOLFOX7 was scheduled after tumor progression in both arms. The primary study end point was duration of disease control (DDC). RESULTS: Median DDC was 13.1 months in patients assigned to the maintenance arm and 9.2 months in patients assigned to the CFI arm (P = .046). Median progression-free survival (PFS) and overall survival were 8.6 and 23.8 months, respectively, in the maintenance arm and 6.6 and 19.5 months, respectively, in the CFI arm. Median duration of maintenance therapy (arm 1) and CFIs (arm 2) were 4.8 months and 3.9 months, respectively. Overall response rates were 59.2% and 59.6% for the initial FOLFOX chemotherapy and 20.4% and 30.3% for FOLFOX reintroduction in arms 1 and 2, respectively. CONCLUSION: The planned complete discontinuation of chemotherapy had a negative impact on DDC and PFS compared with the maintenance therapy strategy. These results suggest that chemotherapy discontinuation cannot be decided before therapy is initiated in patients with advanced colorectal cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Colorrectales/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Cuidados Paliativos , Tasa de Supervivencia , Adulto Joven
8.
Cancer ; 110(12): 2666-71, 2007 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-17963264

RESUMEN

BACKGROUND: Patients older than 75 years of age are usually excluded from metastatic colorectal cancer randomized studies. The OPTIMOX1 study evaluated FOLFOX7, a simplified (s) leucovorin (LV) and 5-fluorouracil (5FU) regimen (sLV5FU2) with high-dose oxaliplatin, in a new oxaliplatin stop-and-go strategy. An exploratory cohort of patients aged 76 to 80 years was included in the study. METHODS: In all, 620 previously untreated patients were randomized between FOLFOX4 until progression (arm A), or FOLFOX7 for 6 cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B). RESULTS: A total of 37 patients aged 76 to 80 years were included, 20 in arm A and 17 in arm B. The overall response rate (ORR) was 59.4%, comparable to younger patients (59%). Median progression-free survival (PFS) was 9.0 months and median overall survival (OS) was 20.7 months. These results did not differ from that in younger patients < or =75 years in the OPTIMOX1 study with PFS 9.0 months (P = .63) and OS 20.2 months (P = .57). They experienced slightly more grade 3 of 4 toxicity than younger patients: 65% versus 48% (P = .06), mainly with more neutropenia (41% vs 24%, P = .03) and neurotoxicity (22% vs 11%, P = .06). Tolerability, however, was manageable and no toxic death occurred in this elderly population. CONCLUSIONS: The efficacy of FOLFOX-based treatment was maintained in patients >75 years with both FOLFOX regimens. The oxaliplatin stop-and-go management strategy performed well in this population.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/patología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios de Cohortes , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Masculino , Metástasis de la Neoplasia , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico , Tasa de Supervivencia
9.
J Clin Oncol ; 25(22): 3224-9, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17664470

RESUMEN

PURPOSE: In the OPTIMOX1 trial, previously untreated patients with advanced colorectal cancer were randomly assigned to two different schedules of leucovorin, fluorouracil, and oxaliplatin that were administered until progression in the control arm or in a stop-and-go fashion in the experimental arm. The randomly assigned treatment groups did not differ significantly in terms of response rate, progression-free survival, and overall survival (OS). However, the impact of oxaliplatin reintroduction on OS was potentially masked by the fact that a large number of patients did not receive the planned oxaliplatin reintroduction or received oxaliplatin after second-line therapy in both treatment groups. PATIENTS AND METHODS: A Cox model was fitted with all significant baseline factors plus time-dependent variables reflecting tumor progression, reintroduction of oxaliplatin, and use of second-line irinotecan. A shared frailty model was fitted with all significant baseline factors plus the number of lines of chemotherapy received by the patient and the percentage of patients with oxaliplatin reintroduction in the center. An adjusted hazard ratio (HR) was calculated for three reintroduction classes (1% to 20%, 21% to 40%, and > 40%), using centers with no reintroduction (0%) as the reference group. RESULTS: Oxaliplatin reintroduction had an independent and significant impact on OS (HR = 0.56, P = .009). The percentage of patients with oxaliplatin reintroductions also had a significant impact on OS. Centers in which more than 40% of the patients were reintroduced had an adjusted HR for OS of 0.59 compared with centers in which no patient was reintroduced. CONCLUSION: Oxaliplatin reintroduction is associated with improved survival in patients with advanced colorectal cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Progresión de la Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxaliplatino , Pronóstico , Modelos de Riesgos Proporcionales , Tasa de Supervivencia , Resultado del Tratamiento
10.
J Clin Oncol ; 25(24): 3732-8, 2007 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-17704423

RESUMEN

PURPOSE: This randomized, 2 x 2 factorial study compared a semimonthly regimen (fluorouracil [FU] and leucovorin [LV] semi-monthly is LV5FU2) with a monthly regimen of FU and LV (mFU/LV) as well as 24 weeks versus 36 weeks of each regimen as adjuvant treatment of stage II and III colon cancer. PATIENTS AND METHODS: LV5FU2 was administered semimonthly for 2 days as racemate (dl) or levogyre (l-; 200 or 100 mg/m(2)) as a 2-hour infusion, followed by 400 mg/m(2) FU bolus and a 600-mg/m(2) FU 22-hour continuous infusion. FU and LV were administered monthly (mFU/LV) for 5 days as dl- or l-LV 15-minute infusion, followed by a 400 mg/m(2) FU 15-minute infusion. The primary end point was disease-free survival (DFS). RESULTS: Between September 1996 and November 1999, 905 patients with stage II (43%) and III (57%) colon cancer were enrolled. The median follow-up was 6 years. There was no statistically significant difference between mFU/LV and LV5FU2 in terms of DFS (150 v 148 events; hazard ratio [HR],1.01; 95% CI, 0.806 to 1.269; P = .94) and overall survival (OS; 104 v 103 events; HR,1.02; 95% CI, 0.77 to 1.34; P = .91). No statistical difference was observed between 24 or 36 weeks of chemotherapy. Median survival from metastatic relapse was 24 months. The survival of patients with metastatic relapse (n = 243) was significantly longer for patients with a longer time from random assignment to relapse (< 1, 1 to 2, >or= 2 years; log-rank test for trend P, .0497). CONCLUSION: DFS and OS were not statistically different between treatment groups and treatment durations. These data confirm the value of LV5FU2 as control arm in the Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer and Pan-European Trials in Adjuvant Colon Cancer studies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Quimioterapia Adyuvante , Neoplasias del Colon/mortalidad , Neoplasias del Colon/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Leucovorina/administración & dosificación , Recurrencia Local de Neoplasia , Pronóstico , Tasa de Supervivencia
11.
Cancer Invest ; 24(2): 154-9, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16537184

RESUMEN

We assessed a schedule alternating 4 FOLFOX and 4 FOLFIRI cycles in 39 patients with 5-FU resistant metastatic colorectal cancer. Patients alternatively received 4 FOLFOX-6 cycles (oxaliplatin 100 mg/m(2), leucovorin 200 mg/m(2) d1 followed by bolus 400 mg/m(2) 5-FU and by a 46-hour 2,400 mg/m(2) 5-FU infusion, every 2 weeks), and 4 FOLFIRI cycles (oxaliplatin replaced by irinotecan 180 mg/m(2) d1) until progression or limiting toxicity. Eigteen patients achieved an objective response (46.1 percent). Median progression-free and overall survivals were 8.8 and 18.7 months, respectively. Only 2 patients (5.1 percent) had Grade 3 oxaliplatin-related sensory-neuropathy. This schedule had so promising efficacy and safety.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/uso terapéutico , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Neoplasias Colorrectales/mortalidad , Resistencia a Antineoplásicos , Femenino , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Resultado del Tratamiento
12.
Bull Cancer ; 93(1): E1-6, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16455499

RESUMEN

METHODS: We evaluated the Epitax combination (epirubicin 60 mg/m2 and docetaxel 75 mg/m2, every 3 weeks) in advanced gastric cancer (AGC) as second-line treatment after fluorouracil and platinum in 50 patients, then as first-line treatment in 36 patients. We report here the results of these two phase II studies. RESULTS: In the second-line treatment, the response rate (RR) was 15.5%. Grade 3-4 neutropenia was observed in 68% (febrile neutropenia in 40%, one treatment-related death). Median time to progression (TTP) and overall survival (OS) were 2.4 and 5.0 months, respectively. In the first-line treatment, the RR was 19.4%. With prophylactic granulocyte colony-stimulating factor, grade 3-4 neutropenia was reported in 38.9%. Then 22 patients received a second-line and 11 patients a third-line treatment. Median TTP and OS were 4.5 and 12 months, respectively. CONCLUSION: Epitax showed moderate activity in AGC. RR in both trials suggests a non-cross resistance with fluorouracil/platinum combination. The 12-month OS in the first-line treatment could be partly explained by early evaluation and active non-cross resistant second-line therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Progresión de la Enfermedad , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neutropenia/inducido químicamente , Neoplasias Gástricas/patología , Análisis de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento
13.
J Clin Oncol ; 24(3): 394-400, 2006 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-16421419

RESUMEN

PURPOSE: In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin. PATIENTS AND METHODS: Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B). RESULTS: Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients. CONCLUSION: Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Compuestos Organoplatinos/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Colorrectales/patología , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Oxaliplatino , Quimioterapia por Pulso , Análisis de Supervivencia , Resultado del Tratamiento
14.
Anticancer Drugs ; 17(10): 1211-7, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17075321

RESUMEN

Intraperitoneal epinephrine above 1 mg/l concentration has been shown to enhance the intratumoral accumulation and antitumor activity of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. The aim of this study was to determine the tolerance of intraperitoneal epinephrine combined with intraperitoneal cisplatin in patients with advanced peritoneal carcinomatosis (17 ovarian cancers, one peritoneal mesothelioma). Intraperitoneal epinephrine (1-5 mg/l) and cisplatin (50 mg/l; 100 mg total dose) were infused in 2 l of saline solution over 2 h. The maximal tolerated concentration of intraperitoneal epinephrine was not reached at 5 mg/l. Cardiovascular symptoms were infrequent and not strictly related to the epinephrine concentration. Tumor responses were obtained in some patients with disease resistant to intravenous platinum compounds. This work demonstrates for the first time that intraperitoneal epinephrine at sufficient concentration enhances the cisplatin effect and can be safely infused into the peritoneal cavity of patients with peritoneal carcinomatosis. The greatest limitation was abdominal pain and limited intraperitoneal distribution of the peritoneal fluid in this closed-abdomen procedure.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma/tratamiento farmacológico , Cisplatino/administración & dosificación , Epinefrina/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma/patología , Cisplatino/efectos adversos , Cisplatino/farmacocinética , Epinefrina/efectos adversos , Epinefrina/farmacocinética , Estudios de Factibilidad , Femenino , Humanos , Infusiones Parenterales/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Resultado del Tratamiento
15.
Bull Cancer ; 93 Suppl 1: S5-9, 2006 Feb 01.
Artículo en Francés | MEDLINE | ID: mdl-16483940

RESUMEN

Oxaliplatin in combination with 5-fluorouracil/leucovorin (LV5FU) improves the response rate and survival of patients with metastatic colorectal cancer. The objective of the Mosaic study was to evaluate the efficacy of this association in the adjuvant treatment of stage II and III colon cancer. This international study, including 2,246 patients, compared the efficacy of standard treatment with LV5FU2 alone to that of oxaliplatin-LV5FU (Folfox4 regimen) following R0 resection of the primary tumour. Both treatments were administered every two weeks for six months. At 3-year follow-up, the risk of relapse was decreased by 23% in the Folfox4 group (p = 0.002). The protocol was well tolerated, with an identical overall mortality during treatment (0.5%) in both groups. The main specific complication, peripheral sensory neuropathy was reversible in the great majority of cases. A new analysis at 4-year follow-up (median 48.6 months) confirmed the superior efficacy of the Folfox4 regimen compared to the standard treatment, the reduction in relapse risk being 24% (p = 0.0008). On the strength of these results, oxaliplatin was granted a marketing authorization for the indication adjuvant treatment of stage III colon cancer. Based on the data currently available, physicians should consider adjuvant treatment for stage II patients, making each individual decision for treatment on a case-by-case basis.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Quimioterapia Adyuvante , Ensayos Clínicos como Asunto , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Oxaliplatino
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