RESUMEN
OBJECTIVE: Azacitidine (Vidaza *) is approved in Europe for treatment of myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) with 20-30% bone marrow (BM) blasts, and chronic myelomonocytic leukemia (CMML) with 10-29% BM blasts and no myeloproliferative syndrome (i.e. <13.000/µL white blood cells). In Belgium, the azacitidine reimbursement process can take several months, and is often delayed at submission for medical assessment by the Belgian National Institute for Health and Disability Insurance of incomplete patient dossiers, due to disease complexity and classification, and administrative burden. We describe the Vidaza Access Program and its application to an initial 175 patients. Individual medical dossiers were reviewed for completeness to facilitate patient access to treatment in Belgium. METHODS: A standardized anonymized patient information form is completed by the physician and sent for review to the Belgian Celgene Medical Department. The form is reviewed within three working days and, for complete dossiers, Celgene grants a financial guarantee for treatment with azacitidine. The patient can then be treated without the hospital being subjected to financial risk. RESULTS: Between January 2013 and June 2014, 63 physicians (53 Belgian hospitals) recruited 175 patients. In total, 163 patient dossiers were approved by Celgene (120 MDS, 36 AML, and 7 CMML), of which 104 dossiers were also approved by the review committee and 49 have been waiting for a final decision for a median of 6 months; no information is currently available for the remaining 10. No dossiers approved by Celgene have been rejected by the review committee. CONCLUSIONS: The Celgene Vidaza Access Program offers support to healthcare professionals in the appropriate use of azacitidine. By facilitating the assessment of patient dossiers and providing a financial guarantee for prescribers and hospitals, treatment can be initiated more rapidly and patients may better benefit from azacitidine treatment.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Accesibilidad a los Servicios de Salud/organización & administración , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bélgica , Femenino , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mielomonocítica Crónica/diagnóstico , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/diagnóstico , Mecanismo de Reembolso/organización & administraciónRESUMEN
OBJECTIVES: We evaluated azacitidine (Vidaza(®)) safety and efficacy in patients with myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and chronic myelomonocytic leukaemia (CMML), in a real-life setting. Treatment response, dose, and schedule were assessed. METHODS: This non-interventional, post-marketing survey included 49/50 patients receiving azacitidine at 14 Belgian haematology centres from 2010-2012. Treatment-emergent adverse events (TEAEs), including treatment-related TEAEs, and serious TEAEs (TESAEs) were recorded throughout the study. Treatment response [complete response (CR), partial response (PR), haematological improvement (HI), stable disease (SD), treatment failure (TF)) and transfusion-independence (TI) were evaluated at completion of a 1-year observation period (1YOP) or at treatment discontinuation, and overall survival (OS), at study conclusion. RESULTS: The median age of patients was 74·7 (range: 43·9-87·8) years; 69·4% had MDS, 26·5% had primary or secondary AML, and 4·1% had CMML. Treatment-related TEAEs, grade 3-4 TEAEs, and TESAEs were reported in 67·3%, 28·6%, and 18·4% of patients, respectively. During 1YOP, patients received a median of 7 (1-12) treatment cycles. Treatment response was assessed for 38/49 patients. Among MDS and CMML patients (nâ=â29), 41·4% had CR, PR, or HI, 41·4% had SD, and 17·2% had TF. Among AML patients (nâ=â9), 44·4% had CR or PR, 33·3% had SD, and 22·2% had TF. TI was observed in 14/32 (43·8%) patients who were transfusion-dependent at baseline. Median (95% confidence interval) OS was 490 (326-555) days; 1-year OS estimate was 0·571 (0·422-0·696). CONCLUSIONS: Our data support previous findings that azacitidine has a clinically acceptable safety profile and shows efficacy.
Asunto(s)
Antimetabolitos Antineoplásicos/uso terapéutico , Azacitidina/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/efectos adversos , Bélgica/epidemiología , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mielomonocítica Crónica/mortalidad , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Vigilancia de Productos Comercializados , Resultado del TratamientoRESUMEN
Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m(-2)) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN+). Median age was 60 years (range 43-75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2-15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48-0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Antineoplásicos Fitogénicos/uso terapéutico , Camptotecina/análogos & derivados , Fraccionamiento de la Dosis de Radiación , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/radioterapia , Adenocarcinoma/cirugía , Adulto , Anciano , Camptotecina/administración & dosificación , Camptotecina/uso terapéutico , Quimioterapia Adyuvante , Terapia Combinada , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/prevención & control , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias del Recto/cirugía , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.
Asunto(s)
Antineoplásicos/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Compuestos de Nitrosourea/administración & dosificación , Compuestos Organofosforados/administración & dosificación , Neoplasias de la Úvea/tratamiento farmacológico , Adulto , Anciano , Femenino , Humanos , Inyecciones Intraarteriales , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana EdadRESUMEN
HER-2/neu oncoprotein contains several major histocompatibility complex class I-restricted epitopes, which are recognised by cytotoxic T lymphocyte (CTL) on autologous tumours and therefore can be used in immune-based cancer therapies. Of these, the most extensively studied is HER-2(9(369)). In the present report, we used dendritic cells pulsed with HER-2(9(369)) to stimulate, in the presence of IL-7 and IL-12, the production of IFN-gamma by patients' CTL detected by the enzyme-linked immunosorbent spot-assay. Frequencies of peptide-specific precursors were estimated in HLA-A2, HLA-A3 and HLA-A26 patients with HER-2/neu-positive (+) breast, ovarian, lung, colorectal and prostate cancers and healthy individuals. We found increased percentages of such precursors in HLA-A2 (25%) and HLA-A26 (30%) patients, which were significantly higher (60%) in HLA-A3 patients. Our results demonstrate for the first time that pre-existing immunity to HER-2(9(369)) occurs in patients with colorectal, lung and prostate cancer. They also suggest that HER-2(9(369)) can be recognised by CTL, besides HLA-A2, also in the context of HLA-A3 and HLA-A26, thus increasing the applicability of HER-2(9(369))-based vaccinations in a considerably broader patients' population.