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1.
Lancet Oncol ; 13(8): e344-52, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22846839

RESUMO

Over the past decade, haematological malignant diseases have been diagnosed with increasing frequency in patients older than 65 years. The management of these diseases is particularly difficult in elderly patients, as non-tumour-related life expectancy is highly variable and the benefit-to-risk ratio for oncological treatments depends on comorbidities and pharmacological factors. Very few data are available in very old or frail patients, and management decisions are usually based on data obtained in younger patients. Patients might, therefore, be overtreated or undertreated without clear clinical or biological justification. In this Review we discuss the management of haematological malignant diseases in the elderly, with respect to biology or pharmacokinetic and pharmacodynamic features. We focus on acute myeloid leukaemia and aggressive lymphoma. Additionally, we discuss how the implementation of geriatric tools, such as comprehensive geriatric assessment scores, in the clinical management of elderly patients might help to adapt treatment to meet individual patients' needs.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Seleção de Pacientes , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Técnicas de Apoio para a Decisão , Avaliação Geriátrica , Nível de Saúde , Neoplasias Hematológicas/patologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Linfoma/tratamento farmacológico , Resultado do Tratamento
2.
Clin Genitourin Cancer ; 19(6): 501-509, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34629300

RESUMO

BACKGROUND: Docetaxel (DOCE) is a standard of care in metastatic castration-resistant prostate cancer (mCRPC). Several retrospective studies suggested a decrease in Prostate Cancer incidence and mortality with metformin (MET). MET has also demonstrated anti-tumor activity in Prostate Cancer preclinical models, with increased apoptosis when added to DOCE. We aimed at exploring the role of MET in combination with DOCE in mCRPC. PATIENTS AND METHODS: Non-diabetic mCRPC patients were randomly assigned to receive DOCE 75 mg/m2 every 21 days + prednisone (5 mg. BID) with either MET 850 mg BID (D+M) or placebo (D+P) up to 10 cycles. Prostate-Specific Antigen (PSA) response ≥50% from baseline was the primary end point. Secondary end points included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), toxicity and quality of life (QoL). RESULTS: Out of 99 patients were randomized (D+M = 50; D+P = 49) in 10 French centers. The median follow-up was 86 (IQR 73-88) months. The PSA-response rate reached 66% in the D+M arm, but was not different from that observed in the D+P arm (63%, P = 0,94). In the D+M and D+P arms, the ORR was 28% and 24%, the median PFS was 7.8 and 6.0 months and the median OS was 27 and 20 months (ns), respectively. Diarrhea grade I to II was more frequent in the MET arm (66% vs. 43%). No impairment of QoL was observed. CONCLUSION: MET addition failed to improve the standard DOCE regimen in mCRPC. Further research targeting tumor cell metabolism should be performed.


Assuntos
Metformina , Neoplasias de Próstata Resistentes à Castração , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Docetaxel/uso terapêutico , Humanos , Masculino , Metformina/uso terapêutico , Prednisona/uso terapêutico , Estudos Prospectivos , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
4.
Int J Radiat Oncol Biol Phys ; 85(5): 1193-9, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23332384

RESUMO

PURPOSE: Stereotactic body radiation therapy (SBRT) allows stereotactic irradiation of thoracic tumors. It may have a real impact on patients who may not otherwise qualify for breast-conserving surgery. We conducted a phase 1 trial that tested 5 dose levels of SBRT concomitant with neoadjuvant chemotherapy (NACT) before to surgery. The purpose of the current dose escalation study was to determine the maximum tolerable dose of SBRT in the treatment of breast cancer. METHODS AND MATERIALS: To define toxicity, we performed dermatologic examinations that included clinical examinations by 2 separate physicians and technical evaluations using colorimetry, dermoscopy, and skin ultrasonography. Dermatologic examinations were performed before NACT, 36 and 56 days after the beginning of NACT, and before surgery. Surgery was performed 4 to 8 weeks after the last chemotherapy session. Efficacy, the primary endpoint, was determined by the pathologic complete response (pCR) rate. RESULTS: Maximum tolerable dose was not reached. Only 1 case of dose-limiting toxicity was reported (grade 3 dermatologic toxicity), and SBRT was overall well tolerated. The pCR rate was 36%, with none being observed at the first 2 dose levels, and the highest rate being obtained at dose level 3 (25.5 Gy delivered in 3 fractions). Furthermore, the breast-conserving surgery rate was up to 92% compared with an 8% total mastectomy rate. No surgical complications were reported. CONCLUSIONS: This study demonstrates that SBRT can be safely combined with NACT. Regarding the efficacy endpoints, this trial showed promising results in terms of pCR rate (36%) and breast-conserving rate (92%). The findings provide a strong rationale for extending the study into a phase 2 trial. In view of the absence of correlation between dose and pCR, and given that the data from dose level 3 met the statistical requirements, a dose of 25.5 Gy in 3 fractions should be used for the phase 2 trial.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Terapia Neoadjuvante/métodos , Radiocirurgia/métodos , Adulto , Idoso , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Marcadores Fiduciais , Humanos , Mastectomia Segmentar/estatística & dados numéricos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Radiodermite/etiologia , Radiodermite/patologia , Radiocirurgia/efeitos adversos , Dosagem Radioterapêutica , Resultado do Tratamento
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