Manila Rubino

Second-line sunitinib as a feasible approach for iodine-refractory differentiated thyroid cancer after the failure of first-line sorafenib

About 5 % of patients with differentiated thyroid cancer (DTC) show RAI-refractory disease, thus having a poor prognosis [1, 2]. Tyrosine-kinase inhibitors (TKIs) has represented a revolution in the management of iodinerefractory DTC [3]. Sorafenib has been the most studied TKI in this field, showing encouraging results in several retrospective and phase II studies [4–8]. Effectiveness of sorafenib in RAI-refractory DTC has been definitely demonstrated in the phase III trial DECISION, where a significant improvement of median progression-free survival (PFS) in the treatment group, as compared with placebo, was reported (10.8 vs 5.8 months; HR 0.58, 95 % CI 0.45–0.75, p\ 0.0001) [9]. Following this finding, sorafenib has became the first TKI approved by the US Food and Drug Administration (FDA) for the treatment of RAIrefractory DTC. Given that the study cohort of the DECISION trial included only TKIs-naive patients, sorafenib can be fully considered the first-line systemic therapy for this clinical setting. Nevertheless, sorafenib has some crucial limits. As reported for all TKIs, it is never curative and has a temporally limited effect. Furthermore, sorafenib induced the development of adverse events leading to drug withdrawal in about 20 % of patients [9]. To date, clear indications about management of RAI-refractory DTC patients after the failure of first-line sorafenib are lacking. Sunitinib is a TKI with a pharmacodynamic profile similar to sorafenib, but broader, targeting RET, c-Kit, VEGFR1, -2, PDGFR-a and -b [10]. Despite few studies have been performed so far, sunitinib seems to be effective for the treatment of RAI-refractory DTC [11–14]. Furthermore, several trials of renal cancer have showed that sunitinib was effective in achieving clinical benefit in the majority of patients who experienced the failure of first-line sorafenib [15], even inducing a longer median PFS. Hence, sunitinib may represent a feasible option as salvage treatment after sorafenib failure also in iodine-refractory DTC. Here we report clinical histories of 3 patients (followed at Federico II University, Department of Clinical Medicine and Surgery, Section of Endocrinology, Naples) with iodinerefractory DTC who were treated with sunitinib after the failure of first-line sorafenib.

Potential role of cinacalcet hydrochloride in sporadic primary hyperparathyroidism without surgery indication

Primary hyperparathyroidism (PHPT) is characterized by the chronic elevation of serum calcium (Ca) levels induced by a long-standing increase of PTH concentrations [1]. Surgical removal of the hyperfunctioning parathyroid tissue represents the only curative approach in this field [2, 3]. Besides symptomatic forms [4], parathyroidectomy (PTx) is indicated in asymptomatic PHPT subjects who have a more advanced disease status. According to the latest update [5], criteria for surgical intervention in asymptomatic PHPT are as follows: (a) serum Ca levels [ 1 mg/dl (0.25 mmol/l) above upper limits of normal; (b) a calculated creatinine clearance \ 60 ml/min; (c) a BMD T score of -2.5 or less at any site or previous fragility fracture (or both); or (d) age \ 50 years. Nevertheless, the management of those patients not having surgery indication is still a point of discussion. Indeed, the 15-year observational study by Rubin et al. [3] has found disease progression in 38 % of this subgroup. This suggests that current surgery criteria are effective in identifying a population with more advanced disease, but cannot effectively predict disease evolution. Cinacalcet hydrochloride is an allosteric modulator of the Ca-sensing receptor (CaSR), where it acts by mimicking an increase in levels of extracellular Ca [6]. In PHPT, this should result in the suppression of PTH secretion [7]. Cinacalcet has been approved in Europe and USA for the management of moderate-to-severe hypercalcemia in patients with PHPT who fulfill surgery indication but are unable to undergo parathyroidectomy [8]. Hence, careful monitoring represents the only indication in PHPT without surgery criteria. We here reported a retrospective, single-center analysis of sporadic PHPT patients who were subjected to treatment with cinacalcet, independently of the surgical indication. Our objective was to provide preliminary insights about the role of cinacalcet in PHPT patients without surgery indication by performing a comparative assessment with PHPTs fitting surgery criteria.

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature

Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs.

Nuove strategie terapeutiche per il trattamento dei NET

SommarioLa strategia terapeutica dei tumori neuroendocrini (NET) comprende la chirurgia per le forme localizzate e le terapie sistemiche per quelle metastatiche o inoperabili. La peculiarità biologica dei NET vede utilizzati in prima linea gli analoghi della somatostatina, anche ad alto dosaggio o in combinazione con gli altri farmaci, gli inibitori delle tirosinochinasi e di mTOR e la terapia radiorecettoriale. Chemioterapia e immunoterapia sono riservate ai NET più aggressivi. Nuovi studi clinici valuteranno, insieme a efficacia e sicurezza, le migliori sequenze terapeutiche.

Medical Therapy in Porotic Patients

Osteoporosis is a multifactorial skeletal disorder characterized by reduced bone mass and deterioration of the micro-architecture of bone. These features predispose affected subjects to increased susceptibility to fractures. According to the World Health Organization, osteoporosis is diagnosed if the bone mineral density (BMD) is 2.5 standard-deviations below the mean peak value in young adults of the same ethnicity and sex (T-score less than −2.5). The “gold standard” for measuring BMD is dual-energy X-ray absorptiometry (DEXA). Other diagnostic modalities include computed tomography (CT), peripheral quantitative CT, and ultrasonography (which has not been shown to provide additional information about bone quality).