Search Results
Search for other papers by Marta Di Stefano in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Carla Colombo in
Google Scholar
PubMed
Search for other papers by Simone De Leo in
Google Scholar
PubMed
Search for other papers by Michela Perrino in
Google Scholar
PubMed
Search for other papers by Mauro Viganò in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Introduction: Lenvatinib (LEN) is a multitarget tyrosine kinase inhibitor currently used for advanced, radioiodine refractory differentiated thyroid cancer (RAI-R DTC). Among adverse events (AEs), nausea, vomiting, and decreased appetite have been frequently described. We aimed to evaluate the prevalence, the clinical presentation, and the effectiveness of conservative treatment of gallbladder disorders in a consecutive series of patient treated with LEN. Methods: Patients with RAI-R DTC experiencing clinical symptoms suggestive for gallbladder disorders during LEN treatment were evaluated with laboratory investigations and contrast-enhanced abdominal computed tomography (CT) and ultrasound scan (US). Results: After a median time of 2 months from the start of treatment, 5/13 patients (38.4%) complained of gastrointestinal symptoms, with increased biliary enzymes levels, especially γGT, and CT/US suggestive of acute cholecystitis (AC). The onset of symptoms and the peak of γGT levels frequently corresponded to the highest reduction in body weight during the first months of treatment. All patients were treated with supportive care and, when appropriate, with ursodeoxycholic acid; in 4 patients, LEN dose reduction or short interruption was needed, too. Conclusions: In patients with RAI-R DTC treated with LEN, a high prevalence of AC in the first months of treatment was documented. Mainly due to the low specificity of symptoms such as anorexia, nausea, and vomiting, this AE is likely to be frequently misdiagnosed. The onset of the disease was associated to the weight loss observed during the first months of treatment and contributes to further decrease in body weight. Therefore, particularly during the first months of treatment, or at any time of huge reduction of body weight, monitoring of γGT and US is crucial for prompt diagnosis and treatment. Conservative medical treatment and LEN dosage titration, together with dietary and rehabilitative supports, can limit or avoid the need for drug withdrawal and cholecystectomy.
Search for other papers by Simone De Leo in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Search for other papers by Carla Colombo in
Google Scholar
PubMed
Search for other papers by Marta Di Stefano in
Google Scholar
PubMed
Search for other papers by Antonella Dubini in
Google Scholar
PubMed
Search for other papers by Silvia Cozzi in
Google Scholar
PubMed
Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Weight loss is one of the most frequent adverse events during treatment with multikinase inhibitors, but scanty data are available on its extent and characteristics. This is the first assessment of the body composition by bioelectrical impedance analysis and of circulating leptin and ghrelin levels, in patients with advanced thyroid cancer before and at regular intervals during treatment with the tyrosine kinase inhibitor lenvatinib. Body mass index (BMI) decreased in all patients, with an average ∆ reduction of –6.4, –9.8, and –15.3% at 3, 6, and 12 months of treatment, respectively. Interestingly, in most patients, after the first year of treatment, BMI remained stable. In all patients, fat mass (FM) reduced more than fat-free mass, the highest decrement being of –60 and –16%, respectively. A decrease in the body cell mass, a parameter mainly due to muscle tissue, was observed only in patients with a vast baseline muscular mass. Total body water decreased in parallel to BMI. During treatment, leptin tightly paralleled the decrease of BMI values, consistent with the decrease in FM, whereas ghrelin levels increased upon BMI decrease. The loss of the FM accounts for the largest portion of BMI reduction during lenvatinib treatment. The increase in ghrelin could account for the BMI stabilization observed after 1 year of treatment. Nevertheless, oral nutritional supplements should be given as early as possible and athletic patients should be encouraged to maintain physical activity. In some circumstances, parenteral nutrition is required for the rehabilitation of these patients.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Carla Colombo in
Google Scholar
PubMed
Search for other papers by Daniele Ceruti in
Google Scholar
PubMed
Search for other papers by Massimiliano Succi in
Google Scholar
PubMed
Search for other papers by Simone De Leo in
Google Scholar
PubMed
Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Matteo Trevisan in
Google Scholar
PubMed
Search for other papers by Claudia Moneta in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Background
Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI).
Aim
The objective was to assess the entire adrenal function in patients on systemic treatments.
Methods
ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases.
Results
After a median treatment period of 7 months, we observed an increase in ACTH values in 80–100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI.
Conclusion
Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Carla Colombo in
Google Scholar
PubMed
Search for other papers by Daniele Ceruti in
Google Scholar
PubMed
Search for other papers by Simone De Leo in
Google Scholar
PubMed
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
Search for other papers by Grzegorz Bilo in
Google Scholar
PubMed
Search for other papers by Matteo Trevisan in
Google Scholar
PubMed
Search for other papers by Noemi Giancola in
Google Scholar
PubMed
Search for other papers by Claudia Moneta in
Google Scholar
PubMed
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
Search for other papers by Gianfranco Parati in
Google Scholar
PubMed
Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Background
Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited.
Aim
The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort.
Methods
Twenty-nine patients were followed up for a mean time of 29.8 months (6–77 months).
Results
After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug.
Conclusion
HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.
