RESUMO
Acute myeloid leukemia (AML) is a disease of the elderly population and survival remains poor after failure of hypomethylating agents (HMA). The BCL-2 inhibitor venetoclax demonstrated activity as monotherapy and in combination with chemotherapy or HMA in AML. In this case series, patients with secondary AML (sAML) not eligible for intensive chemotherapy and refractory to HMA were treated with venetoclax within a named patient program at our tertiary cancer center in Salzburg, Austria. Between April 2017 and September 2018, seven patients with sAML received venetoclax therapy. Two out of seven patients achieved a complete remission upon venetoclax initiation with a PFS of 505 days and 352 days and another patient achieved complete peripheral blood blast clearing within nine days after start of venetoclax. Among the venetoclax responders, primary refractory disease to prior HMA therapy was documented, 2 patients harbored IDH1/IDH2 mutations and one patient had an antecedent myeloproliferative neoplasm. High BCL-2 and/or BIM expression in myeloblasts was found in venetoclax responders and response was significantly associated with overall survival (responders: 364 days versus non-responders: 24 days, P = 0.018). Venetoclax monotherapy is safe and is able to induce durable responses in elderly patients with secondary AML after treatment failure with HMA.
Assuntos
Antineoplásicos/uso terapêutico , Proteína 11 Semelhante a Bcl-2/genética , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Proteína 11 Semelhante a Bcl-2/metabolismo , Biomarcadores Tumorais , Metilação de DNA/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda/diagnóstico , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Indução de Remissão , Retratamento , Resultado do TratamentoRESUMO
BACKGROUND: This multicenter phase II trial was conducted to analyze the clinical activity and toxicity of the combination of pegylated liposomal doxorubicin and vinorelbine as first-line treatment in elderly patients with metastatic breast cancer. PATIENTS AND METHODS: From August 2002 to August 2004, 42 patients with metastatic breast cancer were recruited for treatment with pegylated liposomal doxorubicin 40 mg/m(2) intravenously (i.v.) on day 1 and vinorelbine 30 mg/m(2) i.v. on days 1 and 15 every 4 weeks. RESULTS: The median age of the patients in this trial was 68 years (range 60-82). 40% of patients had 2 or more sites of metastasis, 33 (78%) had predominantly visceral metastasis, and 7 (16%) mostly bone metastasis. Just 2 (5%) patients had only lymphogenous or soft tissue metastasis. All patients had an ECOG performance status of 0-1, but 70% of the patients had relevant comorbidities. In an intention-to-treat analysis, the overall clinical response rate was 36%, the complete response rate was 2%, and the rate of partial remissions was 34%; stable disease occurred in 30%, and progressive disease was observed in 36%. Median duration of response was 10 months. Median time to progression was 4 months, and median overall survival time was 24 months. CONCLUSION: The combination of pegylated liposomal doxorubicin and vinorelbine is an active and well tolerated regimen in elderly patients with metastatic breast cancer in first-line treatment.