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1.
Breast J ; 25(2): 219-225, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30734437

RESUMO

Eribulin is active and safe in heavily pre-treated metastatic breast cancer patients. Few safety data have been published in third line. We aimed to report the specific safety profile on third line beyond taxanes and anthracyclines in advanced breast cancer (ABC). A multicenter phase II, prospective study was conducted in anthracyclines and taxanes pre-treated HER2-negative ABC, programmed to receive eribulin as third-line chemotherapy. Adverse events (AEs) were assessed and classified according to CTCAE. In addition, efficacy, in terms of overall survival (OS) and progression-free survival (PFS), and the dynamics of circulating tumor cells (CTCs) during treatment were assessed. 59 patients fulfilled the criteria. All but one showed AEs with a cumulative number of 598 AEs. The most frequent grade 3/4 drug-related AEs were neutropenia (1.7%), febrile neutropenia (0.5%), leukopenia (0.5%), alopecia (0.5%), asthenia (0.3%), elevated gamma glutamyl transferase levels (0.2%), and respiratory tract infection (0.2%). Median PFS was 4 months (95% CI 3.1-5.9) and median OS was 13.6 months (11.8-not reached). The mean number of CTCs in peripheral blood was significantly reduced from baseline to cycle 2 (16.8 vs 5.4 CTCs; P < 0.001). Median OS was significantly longer in <5 baseline CTC patients compared to ≥5 baseline CTC patients (13.1 months [95% CI: 11.8-not reached] vs 12.5 months [95% CI: 7.6-not reached]; P = 0.045). A significant correlation (P = 0.0129) was observed between CTC levels at cycle 2 and death when CTCs were analyzed using cox regression. Eribulin chemotherapy is effective and safe as third line in advanced HER2-negative breast cancer. CTC levels correlate with overall survival.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Furanos/efeitos adversos , Furanos/uso terapêutico , Cetonas/efeitos adversos , Cetonas/uso terapêutico , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Taxoides/administração & dosagem , Taxoides/uso terapêutico
2.
Melanoma Res ; 31(3): 268-271, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33741812

RESUMO

The emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initially managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.


Assuntos
Proteínas de Fase Aguda/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Imidazóis/efeitos adversos , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Choque/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Choque/mortalidade , Análise de Sobrevida
3.
Tumori ; 107(3): 209-215, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32779517

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is one of the greatest therapeutic challenges of oncology. Potential associations between single nucleotide polymorphisms in heat shock protein ß1 (HSPB1) and transforming growth factor ß1 (TGFß1) and survival have been investigated. METHODS: A prospective multicenter study of 94 patients with SCLC treated between 2013 and 2016 was conducted. Clinical, tumour-related, therapeutic, and genetic (9 SNPs of TGFß1 gene and 5 of HSPB1 gene) variables were analyzed. RESULTS: The cohort included 77 men and 17 women with a median age of 61 years. Eighty percent presented with limited stage at diagnosis and received thoracic radiation with a median dose of 45 Gy (twice-daily radiation in 42%). Forty-seven percent received concurrent platinum-based chemotherapy and 57% received prophylactic cranial irradiation (PCI). Overall survival (OS) was 34% at 2 years and 16% at 3 years. In multivariate analysis, the rs4803455:CA genotype of the TGFß1 gene showed a statistically significant association with lower disease-free survival (DFS; hazard ratio [HR] 3.13; confidence interval [CI] 1.19-8.17; p = 0.020) and higher local recurrence (HR 3.80; CI 1.37-10.5; p = 0.048), and a marginal association with lower OS (HR 1.94; CI 0.98-3.83; p = 0.057). A combined analysis showed that patients receiving PCI and carrying the rs4803455:CA genotype had statistically significant lower OS (p < 0.001) and DFS (p < 0.001) than patients receiving PCI and carrying the rs4803455:AA genotype. CONCLUSIONS: Genetic analysis showed the CA genotype of TGFß1 SNP rs4803455 was associated with worse prognosis in patients with SCLC and could be considered as a potential biomarker.


Assuntos
Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma de Pequenas Células do Pulmão/genética , Fator de Crescimento Transformador beta1/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Irradiação Craniana/métodos , Intervalo Livre de Doença , Feminino , Genótipo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/radioterapia
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