ABSTRACT
Advanced osteosarcomas (OSs) and Ewing sarcomas (ESs) tend to have poor prognosis with limited therapeutic options beyond first-line therapy. Aberrant angiogenesis and MET signaling play an important role in preclinical models. The anti-angiogenic drug cabozantinib was tested in a phase 2 trial of advanced OS and ES and was associated with clinical benefits. We retrospectively analyzed the off-label use of cabozantinib in adult patients with advanced OS and ES/primitive neuroectodermal tumors (PNETs) in three centers of the Hellenic Group of Sarcoma and Rare Cancers (HGSRC). Between April 2019 and January 2022, 16 patients started taking 60 mg of cabozantinib for advanced bone sarcoma or PNET. Median age at cabozantinib initiation was 31 years (17-83). All patients had received peri-operative chemotherapy for primary sarcoma and between 0 and 4 lines of treatment (median; 2.5) for advanced disease. The most common adverse effects included fatigue, anorexia, hypertransaminasemia, weight loss, and diarrhea. One toxic death was noted (cerebral hemorrhage). Dose reduction to 40 mg was required in 31.3% of the patients. No objective response was noted, and 9/16 patients exhibited stable disease outcomes. Progression-free survival varied from 1 to 8 (median; 5) months. Our study demonstrates that cabozantinib has antitumor activity in this population. In the real-life setting, we observed similar adverse events as in the CABONE study and in other neoplasms.
ABSTRACT
BACKGROUND: Elderly patients are underrepresented in the studies concerning anticoagulation therapy (AT) in atrial fibrillation (AF), while patients' frailty status is lacking in most of the studies. OBJECTIVE: Our objective was to evaluate AT in AF elderly patients and study the effect of patients' frailty status on their long-term AT. METHODS: We conducted an observational prospective study that enrolled consecutive AF patients (≥ 75 years) who were hospitalized in the Department of Internal Medicine of the University Hospital of Heraklion, Crete, Greece from 1 June 2015 to 1 June 2016. We recorded the AT on admission and at discharge, all-cause mortality, and hospital readmission in a follow-up period of 1 year after hospital discharge. Frailty status was assessed by pre-established scores. RESULTS: One hundred and four consecutive patients (49% male; median age 87 years) were enrolled, 78 (78.8%) of whom received AT at discharge. Patients who did not receive AT at discharge had a higher HEMORR2HAGES (Hepatic or renal disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or function, Re-bleeding, Hypertension, Anemia, Genetic factors, Excessive fall risk and Stroke) score (5.5 ± 1.15 vs. 4.79 ± 1.68; p = 0.032), a lower Katz score (2.48 ± 2.23 vs. 4.08 ± 2.25; p = 0.006), and a higher Clinical Frailty Scale score (7 ± 1.95 vs. 5.57 ± 2.05; p = 0.006). Sixty-five patients (62.5%) were readmitted to a hospital during the follow-up period. In-hospital death occurred in five patients (4.8%) and 57 patients (57.6%) died within the follow-up period. CONCLUSION: A high percentage of the elderly AF patients did not receive AT, even at discharge. Patients who did not receive AT at discharge had higher bleeding and frailty scores. In the 1-year follow-up period after hospital discharge, high all-cause mortality and a high number of hospital readmissions were recorded.
