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1.
Ann Oncol ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39241959

RESUMEN

BACKGROUND: The administration of adjuvant imatinib during three years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS: IMADGIST (NCT02260505) was a multicenter open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-years arm) compared to Interruption (3-years arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to treat disease-free survival (DFS). Secondary endpoints include overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, safety. RESULTS: From December 24th 2014 to April 4th 2023; 136 patients aged ≥18, ECOG PS ≤2, with a localized GIST with a R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to NCCN risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-Years arm vs. 71 in the 6-Years arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients respectively. Respectively 52 (38%) and 71 (52%) of patients had a risk of relapse of 35-70% and >70%.. With a median follow-up of 55 (IQR=46-59) months post randomization, DFS was significantly superior in the 6-Years arm (HR: 0.40 [0.20-0.69], p=0.0008). Time to imatinib resistance, survival, adverse events and quality of life are not different in the 2 arms. CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

2.
J Eur Acad Dermatol Venereol ; 38(3): 602-612, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38041562

RESUMEN

BACKGROUND: Strategies for the control of scabies should be adapted to local settings. Traditional communities in French Guiana have non-Western conceptions of disease and health. OBJECTIVES: The objectives for this study were to explore knowledge, attitudes and practices to identify potential factors associated with the failure of scabies treatment in these communities. METHODS: Patients with a clinical diagnosis of scabies, seen at either the Cayenne Hospital or one of 13 health centres between 01 April 2021 and 31 August 2021, were included as participants, and were seen again after 6 weeks to check for persistence of lesions. Factors associated with treatment failure were looked for both at inclusion and at 6 weeks. Semi-structured interviews were conducted with a diversified subsample of participants. RESULTS: In total, 164 participants were included in the quantitative component, and 21 were interviewed for the qualitative component. Declaring that the second treatment dose had been taken was associated with therapeutic success. Western treatments were not always affordable. Better adherence was observed with topical treatments than with oral ivermectin, whereas permethrin monotherapy was associated with failure. Scabies-associated stigma was high among Amerindians and Haitians but absent in Ndjuka Maroons. Participants reported environmental disinfection as being very complex. CONCLUSIONS: The treatment of scabies in traditional Guianan communities may vary depending on local perceptions of galenic formulations, disease-associated stigma and differences in access to health care. These factors should be taken into account when devising strategies for the control of scabies aimed at traditional communities living in remote areas, and migrant populations.


Asunto(s)
Indígenas Sudamericanos , Escabiosis , Humanos , Escabiosis/tratamiento farmacológico , Guyana Francesa , Ivermectina , Permetrina
3.
Rev Epidemiol Sante Publique ; 68(2): 125-132, 2020 Apr.
Artículo en Francés | MEDLINE | ID: mdl-32035728

RESUMEN

BACKGROUND: French Guiana faces singular health challenges: poverty, isolation, structural lag, difficulties in attracting health professionals. Hospital stays exceed the recommended durations. The present study aimed to model the impact of precariousness and geographic isolation on the hospital duration performance indicator and to recalculate the indicator after incrementing severity by 1 unit when patients were socially precarious. METHODS: Cayenne hospital data for 2017 were used to model the hospital duration performance indicator (IP-DMS) using quantile regression to study the impact of geographic and social explanatory variables. This indicator was computed hypothesizing a 1 unit increment of severity for precarious patients and by excluding patients from isolated regions. RESULTS: Most excess hospitalization days were linked to precariousness: the sojourns of precarious patients represented 47% of activity but generated 71% of excess days in hospital. Quantile regression models showed that after adjustment for potential confounders, patients from western French Guiana and Eastern French Guiana, precarious patients and the interactions terms between residence location and precariousness were significantly associated with IP-DMS increases. Recalculating the IP-DMSafter exclusion of patients from the interior and after increasing severity by 1 notch if the patient was precarious led to IP-DMS levels close to 1. CONCLUSION: The results show the nonlinear relationship between the IP-DMS and geographical isolation, poverty, and their interaction. These contextual variables must be taken into account when choosing the target IP-DMS value for French Guiana, which conditions funding and number of hospital beds allowed in a context of rapid demographic growth.


Asunto(s)
Vías Clínicas , Accesibilidad a los Servicios de Salud , Tiempo de Internación/estadística & datos numéricos , Pobreza/estadística & datos numéricos , Aislamiento Social , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Vías Clínicas/organización & administración , Vías Clínicas/normas , Vías Clínicas/estadística & datos numéricos , Femenino , Guyana Francesa/epidemiología , Accesibilidad a los Servicios de Salud/organización & administración , Accesibilidad a los Servicios de Salud/normas , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Humanos , Lactante , Recién Nacido , Masculino , Cuerpo Médico/organización & administración , Cuerpo Médico/normas , Cuerpo Médico/estadística & datos numéricos , Cuerpo Médico/provisión & distribución , Persona de Mediana Edad , Administración en Salud Pública/normas , Administración en Salud Pública/estadística & datos numéricos , Derivación y Consulta/organización & administración , Derivación y Consulta/normas , Derivación y Consulta/estadística & datos numéricos , Tiempo de Tratamiento/organización & administración , Tiempo de Tratamiento/normas , Tiempo de Tratamiento/estadística & datos numéricos , Poblaciones Vulnerables/estadística & datos numéricos , Adulto Joven
4.
Epidemiol Infect ; 145(6): 1276-1284, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28091335

RESUMEN

Cervical cancer is the second most frequent cancer in women in French Guiana. Studies have shown that populations living in the remote areas of the interior have early sexual debut and that multiple sexual partnerships are common. The objective of the present study was thus to determine the prevalence of human papillomavirus (HPV) infection in these areas. A study was conducted in women aged 20-65 years with previous sexual activity. Women were included on a voluntary basis after using local media and leaders to inform them of the visit of the team. HPV infection was defined by the detection of HPV DNA using the Greiner Bio-One kit. In addition to HPV testing cytology was performed. The overall age-standardized prevalence rate was 35%. There was a U-shaped evolution of HPV prevalence by age with women aged >50 years at highest risk for HPV, followed by the 20-29 years group. Twenty-seven percent of women with a positive HPV test had normal cytology. Given the high incidence of cervical cancer in French Guiana and the high prevalence of HPV infections the present results re-emphasize the need for screening for cervical cancer in these remote areas. Vaccination against HPV, preferably with a nonavalent vaccine, also seems an important prevention measure. However, in this region where a large portion of the population has no health insurance, this still represents a challenge.


Asunto(s)
ADN Viral/análisis , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/epidemiología , Adulto , Anciano , Técnicas Citológicas , ADN Viral/genética , Estudios Epidemiológicos , Femenino , Guyana Francesa/epidemiología , Genotipo , Técnicas de Genotipaje , Humanos , Persona de Mediana Edad , Papillomaviridae/clasificación , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Prevalencia , Frotis Vaginal , Adulto Joven
5.
Br J Cancer ; 110(5): 1148-54, 2014 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-24407191

RESUMEN

BACKGROUND: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy. METHODS: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%). CONCLUSION: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Mutación , Proteínas Proto-Oncogénicas/genética , Proteínas ras/genética , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Neoplasias Colorrectales/genética , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Proteínas Proto-Oncogénicas p21(ras) , Sorafenib
6.
Ann Oncol ; 25(11): 2205-2210, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25122693

RESUMEN

BACKGROUND: In T3 rectal cancer (RC), preoperative chemoradiotherapy [5-fluorouracil (5-FU-RT)] reduces local recurrences, but does not affect overall survival. New therapeutic options are still necessary to improve clinical outcomes. PATIENTS AND METHODS: This randomized, noncomparative, open-label, multicenter, two arms, phase II study was conducted in MRI-defined locally advanced T3 resectable RC. In arm A, patients received 12-week bevacizumab plus 5-FU, leucovorin and oxaliplatin (Folfox-4) followed with bevacizumab-5-FU-RT before total mesorectal excision (TME). In arm B, patients received only bevacizumab-5-FU-RT before TME. Primary end point was pathological complete response (pCR) rate. RESULTS: Forty-six patients were randomized in arm A and 45 patients in arm B. In arm A, the rate of pCR was 23.8% [95% confidence interval (CI) 12.1% to 39.5%] statistically superior to the defined standard rate of 10%, P = 0.015. In arm B, the rate of pCR of 11.4% (95% CI 3.8% to 24.6%) was not different from 10%, P = 0.906. No death occurred during the study period, from the start until 8 weeks following surgery. Postoperative fistulas were reported for 16 patients (7 in arm A and 9 in arm B). CONCLUSION: Even if the addition of bevacizumab induced manageable toxicities including an increased risk of postoperative fistula and no treatment-related death, arm B did not achieve the expected pCR rate in the population of patients included. Induction bevacizumab-Folfox-4 followed by bevacizumab-5-FU-RT is promising. It is however necessary to continue investigations in the management of locally advanced RC. ClinicalTrials.gov Identifier: NCT 00865189.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Terapia Neoadyuvante , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Recto/tratamiento farmacológico , Adolescente , Adulto , Anciano , Bevacizumab , Desoxicitidina/administración & dosificación , Procedimientos Quirúrgicos del Sistema Digestivo , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Neoplasias del Recto/patología , Neoplasias del Recto/radioterapia , Neoplasias del Recto/cirugía
7.
Ann Oncol ; 25(9): 1762-1769, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25122671

RESUMEN

BACKGROUND: Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. PATIENTS AND METHODS: Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. RESULTS: Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09-0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16-0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6-2.2, P = 0.833). CONCLUSIONS: Primary efficacy analysis ensured the masitinib treatment arm could satisfy a prespecified PFS threshold. Secondary efficacy analysis showed that masitinib followed by the standard of care generated a statistically significant survival benefit over standard of care. Encouraging median OS and safety data from this well-controlled and appropriately designed randomized trial indicate a positive benefit-risk ratio. Further development of masitinib in imatinib-resistant/intolerant patients with advanced GIST is warranted.


Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Tumores del Estroma Gastrointestinal/mortalidad , Inhibidores de Proteínas Quinasas/uso terapéutico , Tiazoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Benzamidas/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Mesilato de Imatinib , Indoles/efectos adversos , Indoles/uso terapéutico , Masculino , Persona de Mediana Edad , Piperazinas/uso terapéutico , Piperidinas , Estudios Prospectivos , Inhibidores de Proteínas Quinasas/efectos adversos , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Piridinas , Pirimidinas/uso terapéutico , Pirroles/efectos adversos , Pirroles/uso terapéutico , Sunitinib , Tiazoles/efectos adversos , Insuficiencia del Tratamiento
8.
Infect Dis Now ; 54(7): 104974, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39255907

RESUMEN

OBJECTIVES: Management of Hepatitis B virus (HBV)-infected patients, whether they are receiving treatment or not, necessitates long-term follow-up. This study evaluated the rate of lost to follow-up (LTFU) among HBV-infected patients and the feasibility of a callback strategy to re-engage these patients in HBV care. PATIENTS AND METHODS: We conducted a retrospective study involving HBV-infected patients attending the outpatient clinic at Cayenne Hospital, French Guiana. LTFU was defined as patients who had not attended the clinic for more than 18 months. A callback strategy was implemented to re-engage LTFU patients in HBV care. RESULTS: Between 1st January 2015 and 31st December 2018, 203 HBV-infected patients were referred to the outpatient clinic; 95/203 (46.8 %) were LTFU, resulting in a crude LTFU rate of 2.6 (95 % CI, 2.1-3.2) per 100 person-years. At baseline, patients aged 30-40 years (aOR, 0.48; 95 %CI, 0.24-0.95) and those who initiated treatment (aOR, 0.26; 95 %CI, 0.10-0.60) were less likely to be LTFU. Through application of the callback strategy, 55/95 (58 %) patients were successfully contacted, and 46/55 (84 %) attended the outpatient clinic for a liver assessment. The EASL criteria for treatment eligibility were met by 3/46 (4 %) patients. Compared to non-LTFU patients, LTFU patients were more likely to be in informal employment (p = 0.03) and to be receiving state medical assistance (p < 0.01), and had lower levels of knowledge about their condition (p < 0.01). CONCLUSIONS: The callback strategy to re-engage LTFU patients in HBV care is feasible and effectively identifies those eligible for antiviral therapy.

9.
Br J Cancer ; 109(10): 2574-8, 2013 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-24149182

RESUMEN

BACKGROUND: Preclinical findings suggest that imatinib mesylate (IM) and metronomic cyclophosphamide (MC) combination provides synergistic antiangiogenic activity on both pericytes and endothelial cells. METHODS: We have designed a 3+3 dose-escalating phase I trial with a fixed dose of MC (50 mg two times daily) plus IM (400 mg per day; 300 and 400 mg two times daily). Enrolled patients had IM- and sutininib-refractory advanced gastrointestinal stromal tumours (GIST) (n=17), chordoma (n=7) and mucosal melanoma (n=2). Dose-limiting toxicities were monitored for the first 6 weeks. Progression-free survival (PFS) and response assessment are based on RECIST 1.0 guidelines. Pharmacokinetics of IM were measured before and after exposure to MC. RESULTS: No dose-limiting toxicity was observed. Fourteen patients of the expanded cohort received 400 mg two times daily of IM with MC. Apart from a case of possibly related acute leukaemia occurring after 4 years of treatment, we did not see unexpected toxicity. No drug-drug pharmacokinetic interaction was observed. There was no objective response. We have observed long-lasting stable disease in chordoma patients (median PFS=10.2 months; range, 4.2-18+) and short-term stable disease in heavily GIST pretreated patients (median PFS=2.3 months; range, 2.1-6.6). CONCLUSION: This combination is feasible and may warrant further exploration in refractory GIST or chordoma patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Benzamidas/administración & dosificación , Ciclofosfamida/administración & dosificación , Neoplasias/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Administración Metronómica , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Benzamidas/efectos adversos , Benzamidas/farmacocinética , Cordoma/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Estudios de Factibilidad , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Mesilato de Imatinib , Masculino , Dosis Máxima Tolerada , Melanoma/tratamiento farmacológico , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Piperazinas/efectos adversos , Piperazinas/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , Neoplasias Cutáneas/tratamiento farmacológico
10.
Ann Oncol ; 24(4): 1087-93, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23175622

RESUMEN

BACKGROUND: We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated. PATIENTS AND METHODS: Within the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed. RESULTS: At data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge. CONCLUSION: In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction.


Asunto(s)
Benzamidas/administración & dosificación , Esquema de Medicación , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Benzamidas/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Piperazinas/efectos adversos , Estudios Prospectivos , Pirimidinas/efectos adversos , Sarcoma/patología , Resultado del Tratamiento
11.
Br J Cancer ; 107(3): 435-41, 2012 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-22767144

RESUMEN

BACKGROUND: Docetaxel and irinotecan chemotherapy have shown good efficacy in the treatment of advanced oesophago-gastric cancer. This randomised phase II study evaluated the efficacy and toxicity profile of two non-platinum docetaxel-based doublet regimens in advanced oesophago-gastric cancer. METHODS: Chemotherapy-naïve patients with advanced oesophago-gastric cancer were randomised to receive either 3-weekly DI (docetaxel 60 mg m(-2) plus irinotecan 250 mg m(-2) (Day 1)) or 3-weekly DF (docetaxel 85 mg m(-2) (Day 1) followed by 5-fluorouracil 750 mg m(-2) per day as a continuous infusion (Days 1-5)). RESULTS: A total of 85 patients received DI (n=42) or DF (n=43). The primary endpoint was overall response rate (ORR). The ORR and time to progression (TTP) in the evaluable population (n=65) were 37.5% (DI) vs 33.3% (DF), and 4.2 months vs 4.4 months, respectively. In the intent-to-treat population, the observed ORR, TTP and median overall survival were similar between the two groups. Grade 3-4 neutropenia, febrile neutropenia and diarrhoea were more frequent in the DI arm as compared with the DF arm (83.3% vs 69.8%, 40.5% vs 18.6%, and 42.9% vs 16.3%, respectively). CONCLUSION: Both docetaxel-based doublet regimens show comparable efficacy; however, the DF regimen was associated with a better toxicity profile and is an alternative treatment option for patients in whom platinum-based regimens are unsuitable.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Progresión de la Enfermedad , Docetaxel , Femenino , Fluorouracilo/administración & dosificación , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Taxoides/administración & dosificación
12.
Ann Oncol ; 23(4): 919-27, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21825101

RESUMEN

BACKGROUND: We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. RESULTS: By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CONCLUSION: CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Células Endoteliales/patología , Endotelio Vascular/patología , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Capecitabina , Recuento de Células , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/mortalidad , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Femenino , Citometría de Flujo , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Irinotecán , Estimación de Kaplan-Meier , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Metástasis de la Neoplasia , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
14.
Br J Cancer ; 102(8): 1207-12, 2010 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-20354522

RESUMEN

BACKGROUND: To evaluate the antitumour activity and safety of metronomic cyclophosphamide vs megestrol acetate in progressive and advanced cancer patients having exhausted all effective therapies under standard care. METHODS: Patients were randomly assigned to receive orally metronomic cyclophosphamide (50 mg b.i.d) or megestrol acetate (160 mg only daily) until intolerance or progression (RECIST 1.0). The primary efficacy end point was a 2-month progression-free rate (PFR(2m)). According to Optimal Simon's design and the following assumptions, namely, P0=5%, P1=20%, alpha=beta=10%, the treatment is considered as effective if atleast 5 out of 44 patients achieved PFR(2m). RESULTS: Between September 2006 and January 2009, 88 patients were enrolled. Two patients experienced grade 3-4 toxicities in each arm (4%). One toxic death occurred in the megestrol acetate arm as a consequence of thrombosis. The metronomic cyclophosphamide arm reached the predefined level of efficacy with a PFR(2m) rate of 9 out of 44 and a PFR(4m) rate of 5 out of 44. The MA arm failed to achieve the level of efficacy with a PFR(2m) of 4 out of 44 and a PFR(4m) of 1 out of 44. The median overall survival was 195 and 144 days in the metronomic cyclophosphamide arm and megestrol acetate arm, respectively. CONCLUSION: Metronomic cyclophosphamide is well tolerated and provides stable disease in such vulnerable and poor-prognosis cancer patients. This regimen warrants further evaluations.


Asunto(s)
Antineoplásicos Alquilantes/administración & dosificación , Antineoplásicos Hormonales/uso terapéutico , Ciclofosfamida/administración & dosificación , Acetato de Megestrol/uso terapéutico , Neoplasias/tratamiento farmacológico , Anciano , Antineoplásicos Hormonales/administración & dosificación , Ciclofosfamida/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Humanos , Masculino , Acetato de Megestrol/efectos adversos , Persona de Mediana Edad , Neoplasias/mortalidad , Cuidados Paliativos
15.
Br J Cancer ; 102(1): 59-67, 2010 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-19920832

RESUMEN

BACKGROUND: A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients. METHODS: Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit. RESULTS: A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P<0.001; C6/C8, P=0.009) and satisfactory to patients (C6/C8, P=0.003) than FOLFOX-6. At the final visit, XELOX patients spent fewer days on hospital visits (3.3 vs 5.3 days, P=0.045) and lost fewer hours of work/daily activities (10.2 vs 37.1 h lost, P=0.007). CONCLUSION: XELOX has a similar QoL profile, but seemed to be more convenient in terms of administration at certain time points and reduced time lost for work or other activities compared with FOLFOX-6.


Asunto(s)
Adenocarcinoma/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/psicología , Calidad de Vida , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/psicología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Capecitabina , Neoplasias Colorrectales/tratamiento farmacológico , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Fluorouracilo/análogos & derivados , Humanos , Leucovorina/administración & dosificación , Leucovorina/efectos adversos , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/efectos adversos , Oxaloacetatos , Satisfacción del Paciente , Estudios Prospectivos , Encuestas y Cuestionarios
16.
Br J Cancer ; 103(9): 1349-55, 2010 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-20940718

RESUMEN

BACKGROUND: Concurrent chemoradiotherapy is a valuable treatment option for localised oesophageal cancer (EC), but improvement is still needed. A randomised phase II trial was initiated to assess the feasibility and efficacy in terms of the endoscopic complete response rate (ECRR) of radiotherapy with oxaliplatin, leucovorin and fluorouracil (FOLFOX4) or cisplatin/fluorouracil. METHODS: Patients with unresectable EC (any T, any N, M0 or M1a), or medically unfit for surgery, were randomly assigned to receive either six cycles (three concomitant and three post-radiotherapy) of FOLFOX4 (arm A) or four cycles (two concomitant and two post-radiotherapy) of cisplatin/fluorouracil (arm B) along with radiotherapy 50 Gy in both arms. Responses were reviewed by independent experts. RESULTS: A total of 97 patients were randomised (arm A/B, 53/44) and 95 were assessable. The majority had squamous cell carcinoma (82%; arm A/B, 42/38). Chemoradiotherapy was completed in 74 and 66%. The ECRR was 45 and 29% in arms A and B, respectively. Median times to progression were 15.2 and 9.2 months and the median overall survival was 22.7 and 15.1 months in arms A and B, respectively. CONCLUSION: Chemoradiotherapy with FOLFOX4, a well-tolerated and convenient combination with promising efficacy, is now being tested in a phase III trial.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Terapia Combinada , Neoplasias Esofágicas/mortalidad , Femenino , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Humanos , Leucovorina/efectos adversos , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Compuestos Organoplatinos/efectos adversos , Compuestos Organoplatinos/uso terapéutico
17.
Eur J Cancer ; 111: 12-20, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30798084

RESUMEN

PURPOSE: The role of chemotherapy has not been established in the treatment of metastatic squamous cell oesophageal cancer (mESCC). PATIENTS AND METHODS: E-DIS is a discontinuation trial, aimed at estimating efficacy, quality of life and safety of chemotherapy continuation (CT-CONT) in patients with mESCC who are free from progression after a selection phase of chemotherapy. The primary end-point was overall survival. RESULTS: Sixty-seven patients were randomised. The 9-month survival rate was 50% (85% confidence interval [CI]: 37-62%) and 48% (85% CI: 35-60%) in the CT-CONT arm and in the chemotherapy discontinuation (CT-DISC) arm, respectively. The time until definitive deterioration of the global health status (European Organisation for Research and Treatment of Cancer [EORTC] core quality of life questionnaire) was 6.6 months (95% CI: 3.3-12.4) for the CT-CONT arm and 4.2 months (95% CI: 2.9-6.3) for the CT-DISC arm, with a hazard ratio (HRCT-DISC/CT-CONT) = 1.44 (95% CI: 0.82-2.53). We observed a beneficial trend in favour of CT-CONT (HR > 1) for most dimensions, including an improvement for three dimensions (dysphagia, eating and oesophageal pain) of the EORTC Oesophageal Cancer Module QLQ-OES18. CONCLUSION: CT-CONT provides an overall survival rate that is similar to CT-DISC. E-DIS trial provides valuable data to support shared decision-making between physicians and patients regarding CT-CONT/DISC.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Resultado del Tratamiento
18.
Clin Oncol (R Coll Radiol) ; 20(7): 523-7, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18440792

RESUMEN

AIMS: The multidisciplinary medical decision-making process is a key element of the clinical management of cancers, especially rare cancers such as visceral and soft tissue sarcomas. One of the most important decisions stated is to discriminate patients considered for palliative-intent treatment. The aim of this retrospective study was to establish the rationale parameters that justify this decision for newly diagnosed sarcomas. PATIENTS AND METHODS: From a retrospective cohort of 341 patients we investigated the parameters justifying a palliative-intent strategy decision in univariate and multivariate analyses, based on the logistic regression model. We also measured the effect of this decision on overall survival using the Cox model. RESULTS: Seventy-one of 341 patients (20%) were considered for a palliative-intent strategy. In multivariate analysis, five variables justified this decision: contraindication for general anaesthesia (adjusted odds ratio 10.5), head and neck location (odds ratio 3.7), visceral sarcoma (odds ratio 2.8), tumour size over 8 cm (odds ratio 3.5) and presence of metastasis (odds ratio 39.5). In the Cox model we found that two independent factors were associated with poor outcome: grade 3 (hazard ratio 2.7) and palliative-intent strategy (hazard ratio 3.3). CONCLUSIONS: About 20% of newly diagnosed sarcomas were considered for palliative strategy by multidisciplinary committee. This decision was based on rationale parameters and had an intrinsic prognostic value.


Asunto(s)
Toma de Decisiones , Cuidados Paliativos/psicología , Neoplasias de los Tejidos Blandos/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Comunicación Interdisciplinaria , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Análisis de Supervivencia
19.
J Chir (Paris) ; 145 Suppl 3: 6S12-7, 2008.
Artículo en Francés | MEDLINE | ID: mdl-19060843

RESUMEN

The management and the prognosis of gastrointestinal stromal tumors (GIST) have evolved rapidly with new targeted treatments. The aim of this paper is to assess the role of imaging not only for diagnosis but to quantify treatment response. RECIST criteria, which are the standard in assessment of post chemotherapy response in adult's solid tumors, can not be used in targeted therapy: the changes in lesion structures even if case of increasing volume are more specific to assess tumor response.


Asunto(s)
Tumores del Estroma Gastrointestinal/diagnóstico , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
20.
J Chir (Paris) ; 145S3: 6S12-7, 2008.
Artículo en Francés | MEDLINE | ID: mdl-22793865

RESUMEN

S. Taïeb, L. Ceugnart, F. Bonodeau, L. Vanseymortier, A. Adenis The management and the prognosis of gastrointestinal stromal tumors (GIST) have evolved rapidly with new targeted treatments. The aim of this paper is to assess the role of imaging not only for diagnosis but to quantify treatment response. RECIST criteria, which are the standard in assessment of post chemotherapy response in adult's solid tumors, can not be used in targeted therapy: the changes in lesion structures even if case of increasing volume are more specific to assess tumor response.

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