We performed lymphoscintigraphy in 15 patients (newborns and children) affected by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is mandatory in all patients with signs of ...lymphatic dysplasia, including those with minimal and initial signs of lymphatic impairment, to obtain very early diagnosis and begin treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Lung cancer is still the leading cause of cancer related death worldwide. Fibroblast growth factor receptor (FGFR) is a tirosine-kinase receptor that is seen to be amplified or mutated in non-small ...cell lung cancer (NSCLC) and it plays a crucial role in tumour development and maintenance. The authors analyzed the state of the art of FGFR by reviewing the current literature. Fibroblast growth factor (FGF)-FGFR pathway and their aberrations are described, with the evaluation of their possible prognostic role in NSCLC and in particular in squamous cell carcinomas, in which FGFR is more often amplified. New therapeutic agents targeting FGFR signaling have been developed and are now in clinical evaluation. Dysregulation of FGF signaling in tumour cells is related to FGFR gene amplification or mutation, although it is still uncertain which of these aberrations represents a real predictor of response to specific inhibitors. However, recent evidence has questioned whether FGFR is a real target in squamous cell histology. The effectiveness of FGFR inhibitors is also still unclear since there are no clinical data on selected patients. Moreover, the management of specific side effects related to inhibition of the physiological role of FGF should be more thorough.
Introduction:
The inhibition of the epidermal growth factor receptor (EGFR) through tyrosine kinase inhibitors (TKIs) represents an effective strategy for EGFR-mutated NSCLC. Afatinib is an ...irreversible erythroblastosis oncogene B (ErbB) family blocker, able to inhibit the kinase domains of EGFR, HER2 and HER4, and the transphosphorylation of ErbB3 that has recently been approved in the United States for the first-line treatment of EGFR-mutated NSCLC and in Europe and Japan for the treatment of EGFR-mutated TKI-naive patients.
Areas covered:
The authors analyzed the pharmacology and the clinical activity of afatinib in NSCLC through a review of the literature. Trials exploring different settings have been reported, including LUX-Lung 3 and LUX-Lung 6, where the drug achieved better outcomes in terms of response rate, progression-free survival and quality of life compared with chemotherapy. The main toxicities of afatinib are gastrointestinal and skin-related adverse events.
Expert opinion:
Afatinib showed remarkable efficacy as a first-line treatment in the presence of common EGFR mutations. Afatinib showed some activity in NSCLC with acquired resistance to EGFR TKIs, although, currently, its efficacy after the failure of erlotinib or gefitinib has not been clearly stated. Direct clinical data comparing the activity and tolerability of different inhibitors are still needed.
Introduction:
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. Although advanced NSCLC is still incurable, various anti-neoplastic agents have become available ...for the treatment of this disease. Pemetrexed, a multi-target folate antagonist, has improved the survival of non-squamous NSCLC patients. Currently, pemetrexed is approved for first-line treatment in combination with a platinum derivate, for second-line treatment as a single agent and, more recently, as maintenance treatment after first-line chemotherapy.
Areas covered:
The authors analyzed the state of the art of pemetrexed through a review of the literature. Clinical trials and meta-analyses involving pemetrexed in NSCLC were evaluated. Pemetrexed improved survival of non-squamous NSCLC in first-line, maintenance, and second-line treatments; this benefit is limited to non-squamous histology. Because pemetrexed has become part of the standard of care, current clinical trials are designed to compare it to other investigational combinations. Limited data on resectable disease are available, and additional clinical trials are being conducted.
Expert opinion:
Pemetrexed has shown effectiveness and a favorable toxicity profile. Histology-driven indications and the relationship of pemetrexed with thymidylate synthase expression suggest that a more precise definition of predictive biomarkers could be further investigated.
Background:
The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with ...abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes.
Methods:
This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS).
Results:
Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml (p = 0.007), Gleason Score >7 (p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 (p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months (p = 0.01), and body mass index (BMI) > 25 (p = 0.03) were associated with worse PFS; presence of pain (p = 0.01), ECOG PS1–2 (p = 0.004), duration of ADT ⩽ 43.2 (p = 0.05), and BMI > 25 (p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders (p = 0.001) and fluid retention (p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS (p = 0.036). Similar associations were observed after stratification by subgroup.
Conclusions:
Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.
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