Valproic Acid, a Histone Deacetylase Inhibitor, in Combination with Paclitaxel for Anaplastic Thyroid Cancer: Results of a Multicenter Randomized Controlled Phase II/III Trial

Anaplastic thyroid cancer (ATC) has a median survival less than 5 months and, to date, no effective therapy exists. Taxanes have recently been stated as the main drug treatment for ATC, and the histone deacetylase inhibitor valproic acid efficiently potentiates the effects of paclitaxel in vitro. Based on these data, this trial assessed the efficacy and safety of the combination of paclitaxel and valproic acid for the treatment of ATC. This was a randomized, controlled phase II/III trial, performed on 25 ATC patients across 5 centers in northwest Italy. The experimental arm received the combination of paclitaxel (80 mg/m2/weekly) and valproic acid (1,000 mg/day); the control arm received paclitaxel alone. Overall survival and disease progression, evaluated in terms of progression-free survival, were the primary outcomes. The secondary outcome was the pharmacokinetics of paclitaxel. The coadministration of valproic acid did not influence the pharmacokinetics of paclitaxel. Neither median survival nor median time to progression was statistically different in the two arms. Median survival of operated-on patients was significantly better than that of patients who were not operated on. The present trial demonstrates that the addition of valproic acid to paclitaxel has no effect on overall survival and disease progression of ATC patients. This trial is registered with EudraCT 2008-005221-11

Cardiometabolic Risk, Part 2:Indirect Cardiotoxicity in Cancer Survivors - The Emerging Role of Metabolic Syndrome

Cardiovascular diseases represent one of the most common and serious late complications of anticancer treatments. In the general population, metabolic syndrome is closely related to the risk of cardiovascular events and mortality. In recent years, metabolic syndrome has gained attention as a crucial determinant of long-term cardiovascular risk in cancer survivors. Several risk factors have been associated with metabolic syndrome after cancer treatments, even if the pathophysiological mechanisms of this association are not fully understood. This chapter reviews the clinical features of metabolic syndrome in cancer survivors, analyzing in more detail patients treated with hormonal therapy and survivors of hematopoietic stem cell transplantation, who are burdened with a greater cardiovascular risk. Moreover, the role of lifestyle factors in the development of metabolic syndrome is discussed as well as the screening strategy for the early detection of metabolic alterations in cancer survivors. Finally, we discuss the available recommendations for cardiovascular risk assessment in cancer survivors and treatments for metabolic syndrome in this specific context

Surgical treatment of anaplastic thyroid carcinoma. Our experience

Introduzione. Nel carcinoma anaplastico della tiroide (ATC) l’exeresi chirurgica associata a chemio- e radioterapia può migliorare il controllo locale della malattia con occasionali lunghe sopravvivenze. Pazienti e metodi. In 20 pazienti con ATC è stato possibile effettuare la resezione del tumore, senza residui macroscopici (13 casi) o con minimi residui su strutture vitali infiltrate (7 casi); 10 di questi pazienti (50%) avevano già metastasi a distanza. Sedici casi sono stati trattati anche con chemio- e radioterapia; in uno è stata possibile solo la chemioterapia; 2 pazienti hanno rifiutato ulteriori terapie; uno sta per iniziare la terapia adiuvante. Sono state analizzate morbilità e sopravvivenza, anche confrontando questi casi con altri 15 ATC sottoposti a exeresi incompleta del tumore cervicale o non operati affatto (gruppo di controllo). Risultati. La funzione di almeno un nervo laringeo ricorrente è stata salvaguardata in tutti i casi, e nessuno ha avuto un ipoparatiroidismo permanente. Al termine dello studio 17 pazienti erano morti e 3 erano vivi a 1, 6 e 80 mesi dall’intervento; quest’ultimo caso è libero da malattia. La sopravvivenza dei pazienti deceduti varia fra 3 e 28 mesi (media: 8 mesi). Nel gruppo di controllo tutti i pazienti erano deceduti, con sopravvivenze comprese fra 1 e 13 mesi (media: 4 mesi). L’analisi attuariale della sopravvivenza ha dimostrato una significativa differenza fra i due gruppi (p = 0.0112); un’analisi multifattoriale di diversi fattori prognostici ha confermato che il più rilevante era l’exeresi completa o quasi completa del tumore. Conclusioni. La resezione chirurgica è una componente importante del trattamento multimodale dell’ATC e dovrebbe essere tentata ogniqualvolta possibile

Stress Axis in the Cancer Patient: Clinical Aspects and Management

Hypothalamus–pituitary–adrenal (HPA) axis alterations are common in cancer patients, mainly due to the different antitumoral therapies, which lead to several acute and late endocrine side effects. This review summarizes the most recent evidence regarding HPA derangement, both in patients with active neoplasms and in cancer survivors, with particular attention to the impact of the different antitumoral treatments, focusing on the major clinical aspects. While acute hormone failure usually results from injury caused directly by tumor burden or surgical interventions, short- and long-term effects are generally due to chemotherapy, radiotherapy and, as more recently shown, to different types of targeted- and immuno-therapy. Adrenal insufficiency (AI) is mostly caused by pituitary or hypothalamic injury rather than a direct damage of the adrenal gland. Moreover, other treatments commonly employed as supportive therapy or in the context of palliative care (i.e., glucocorticoids, opioids) can lead to HPA dysfunction. Epidemiology and pathophysiology of stress axis alterations in cancer patients still require clarification. Since AI may represent a life-threatening condition, monitoring adrenal function in cancer patients is mandatory, especially in subjects who experience fatigue or during stress conditions, in order to promptly start replacement treatment when needed