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Lung Cancer ; 127: 12-18, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30642539


The onset of a new histology is a resistant mechanism to tyrosine kinase inhibitors (TKI) in lung adenocarcinoma (ADK), but this phenomenon has not yet been fully clarified. We present a pooled analysis of the outcomes of EGFR-mutated ADK patients with changed phenotype to squamous cell carcinoma (SqCC) following TKI, along with the description of an additional case. A 67-year-old woman with EGFR-mutated NSCLC received gefitinib and subsequently osimertinib, due to the presence of T790 M at progression. The re-biopsy after third-generation TKI revealed SqCC histology along with the basal EGFR mutation, while T790 M disappeared. The patient rapidly progressed and died despite two chemotherapy cycles. Since this first description of SqCC transformation appearing after treatment with the third-generation TKI osimertinib, other 16 patients, with EGFR-mutated ADK developing a transformation to SqCC histology after treatment with TKIs, were up to now published. From our pooled analysis emerged that most patients were female (82%), 41% were former smokers and no current smokers were identified. Median time to SqCC onset was 11.5 months. In all cases, basal EGFR mutation was maintained, and 11 patients (65%) developed an acquired mutation on exon 20. Interestingly also 790 M mutation appeared in 8 patients (47%). The median survival after SqCC diagnosis was 3.5 months regardless the treatments received. Therefore, EGFR-mutated lung ADK destined to develop a squamous phenotype were often smokers and maintained the baseline genomic alterations. The prognosis after SqCC diagnosis was extremely poor and current treatments largely inefficacious.

Eur J Cancer Care (Engl) ; 28(2): e12978, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30536872


Port-a-cath (PAC) system is one of the most frequently employed venous accesses for administration of chemotherapy and supportive care. To prevent late complications, the latest guidelines recommend flushing/locking procedures every four weeks. In this retrospective study, we evaluate the frequencies of late complications with a eight-week flushing/locking procedure compared to the standard one. This study retrospectively compares the frequency of complications occurred using standard versus delayed flushing schedules. We performed a systematic review of the published studies about PAC complications associated with longer flushing intervals. Three hundred and ninety fully available patients were enrolled. One hundred and six patients had their PAC flushed/locked every month, 347 patients performed the flushing/locking procedures every eight weeks, 63 patients switched from the four to the eight-week schedule. No difference was seen in the number of occlusions, infections and mechanical dysfunctions between the two patient groups. The systematic literature review confirmed, in a total of 1,347 patients, the absence of an increased proportion of complications with delayed schedules. PAC flushing and locking every eight weeks are feasible and safe. This delayed schedule may improve patients' quality of life and decrease both nursing workload and costs for the national health system.

Infecções Relacionadas a Cateter/prevenção & controle , Controle de Infecções/métodos , Neoplasias/tratamento farmacológico , Dispositivos de Acesso Vascular , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Descontaminação/métodos , Remoção de Dispositivo , Feminino , Heparina/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Solução Salina/administração & dosagem , Fatores de Tempo , Adulto Jovem
Support Care Cancer ; 26(8): 2929-2935, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29546526


PURPOSE: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity. METHODS: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS). RESULTS: A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped. CONCLUSION: This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.

Acetilcisteína/uso terapêutico , Antineoplásicos Alquilantes/toxicidade , Fígado/patologia , Sarcoma/complicações , Trabectedina/toxicidade , Acetilcisteína/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/tratamento farmacológico , Sarcoma/patologia