Efficacy of sorafenib and impact on cardiac function in patients with thyroid cancer: a retrospective analysis.

PURPOSE: Sorafenib has recently been recognized as an important standard option for the management of patients with differentiated thyroid cancer. Although data concerning cardiac safety are available in pan-tumor studies, no data are available on its use in everyday clinical practice in patients with thyroid cancer. METHODS: In the off-label program of our institution, we enrolled 14 patients with different histological types of thyroid cancer suitable for treatment with sorafenib. Our aims were to evaluate cardiac safety factors-LVEF (left ventricular ejection fraction), heart rate and blood pressure-the cardiac markers NT-proBNP and troponin I, radiological response evaluated by CT and (18)FDG-PET (according to RECIST 1.1 criteria) and biomarker reduction (Eastern Cooperative Oncology Group Performance Status: ECOG PS) 0-2. RESULTS: Patients with ECOG PS 2 accounted for 36%. After starting sorafenib, many patients displayed reduced or stabilized metabolic activity in target lesions (clinical benefit = 44%), radiologic reduction or stabilization (74%) and decreased cancer markers (90%). Lung metastases displayed the largest reductions in size. Median overall survival (OS) was 7 months and median progression-free survival (PFS) was 3 months. No sign of cardiotoxicity was observed in almost all patients. LVEF was altered in two patients and proved symptomatic in one. CONCLUSIONS: Sorafenib seems to be effective in reducing disease progression in the early stages of treatment (3-6 months). Responses varied considerably according to the criteria investigated. Cardiac toxicities did not raise concerns and were in line with data reported in other malignancies. However, cardiac monitoring is recommended.

Long-term outcome after radioiodine therapy with adjuvant rhTSH treatment: comparison between patients with non-toxic and pre-toxic large multinodular goitre.

In multinodular goitre (MNG), low radioiodine (RAI) activity after recombinant human (rh) TSH is able to reduce thyroid volume (TV) and improve symptoms. Our aim was to evaluate the long-term outcome of RAI after rhTSH treatment in patients who were divided according to their baseline TSH levels. Eighteen patients (69.2 ± 6.1 year) presented non-toxic (TSH >0.3 mIU/l) MNG (TV: 61.0 ± 3.8 ml; group 1), while 13 patients (74.1 ± 7.9 year) had non-autoimmune pre-toxic (TSH <0.3 mIU/l) MNG (TV: 82.6 ± 14.4 ml; group 2). TSH, thyroid hormones, TV (by ultrasonography), body mass index (BMI), symptoms and quality of life (QoL) were evaluated. Treatment induced short-term thyrotoxicosis in both groups, but this was slightly more marked in group 2 than in group 1. The number and severity of adverse events were similar. The follow-up period was 55.3 ± 4.1 months in group 1 and 57.2 ± 5.1 months in group 2. The final TV reduction was similar in groups 1 (63.4 ± 3.6%) and 2 (57.2 ± 4.6%) and TV reduction positively correlated only with initial TV. At the last examination, 14 group-1 subjects were on L-T4 therapy, while 2 group-2 subjects were on methimazole. An increase in BMI was noted only in group 2. MNG-related symptoms were significantly reduced in both groups. Symptoms related to sub-clinical hyperthyroidism improved in group 2, while no significant changes in QoL were noted in either group. This study confirms the effectiveness of rhTSH adjuvant treatment in reducing TV after low RAI activities, irrespective of baseline thyroid status. TSH levels <0.3 mIU/l proved to be predictive of a more severe thyrotoxic phase after rhTSH and RAI, while initial TSH levels >0.3 mIU/l were more frequently followed by a need for L-T4 therapy. Compressive symptoms improved in the majority of subjects.

Safety and efficacy of administering 0.2 mg of recombinant human TSH for two consecutive days as an adjuvant to therapy with low radioiodine doses in elderly out-patients with large nontoxic multinodular goiter.

AIM: The aim of this study was to evaluate the efficacy of recombinant human TSH (rhTSH) as an adjuvant to radioiodine therapy for nontoxic multinodular goiter (MNG) in elderly subjects. METHODS: Twelve elderly out-patients with large MNG (group 1) were studied. The effect of adjuvant rhTSH administration (0.2 mg i.m. on 2 consecutive days) before low-dose (131)I was compared with that of radioiodine alone in 8 out-patients matched for age and MNG volume (group 2). The follow-up period was similar in both groups. RESULTS: The number and severity of side-effects during the first month of treatment were similar in both groups. On final examination, the number of patients symptomatic for goiter was significantly lower in group 1 than in group 2 (P=0.03). In group 1, TSH levels peaked at 40.3+/-9.5 mU/L on day 3, from the baseline value of 0.5+/-0.1 mU/L (P<0.001). In group 2, baseline TSH was 0.4+/-0.1 mU/L. Although a marked increase in f-T3, f-T4 and Tg (P<0.001) was noted in both groups during the first 2 weeks of treatment, peak values were much higher in group 1 than in group 2. On final examination, a slightly significant increase (P=0.01) in TSH levels from the baseline was noted in both groups (group 1: 1.2+/-0.2 mU/L; group 2: 1.4+/-0.3 mU/L). The percentage of patients who did not need therapies to control TSH secretion at the last examination was higher in group 1 (83%) than in group 2 (38%). Only in group 1, a significant reduction was noted in mean anterior-posterior lobar width (31+/-1.7 mm) from the baseline value (24.5+/-1.7 mm, P=0.04). Thyroid volume was reduced from 78.1+/-11.7 mL to 49.4+/-13.4 mL (P=0.001) in group 1 and from 89.8+/-25.2 mL to 67.1+/-20.5 mL (P=0.04) in group 2. Six months after (131)I therapy, slight changes in thyroid length and tracheal lumen were noted in both groups. CONCLUSIONS: This long-term controlled study demonstrates that 0.2 mg of rhTSH on 2 consecutive days increases the efficacy of ambulatory (131)I dosages in treating nontoxic MNG in elderly subjects. Adequate drug preparation generally prevents side-effects due to short-term but marked thyrotoxicosis that is aggravated by rhTSH administration. An increase in thyroid volume reduction seems to be the most important effect of rhTSH administered before (131)I.

Effects of growth hormone administration in addition to gonadotrophins in normally ovulating women and polycystic ovary syndrome (PCO) patients.

Follicular fluid sex-steroids, insulin-like growth factor-I (IGF-I), IGF-I binding protein (IGF-I-BP) and epidermal growth factor were investigated in patients with polycystic ovaries and normally ovulating women, following ovulation induction with gonadotrophins or growth hormone plus gonadotrophins. Growth hormone supplementation enhanced the ovarian response to gonadotrophins, and significantly increased follicular fluid IGF-I in both groups, without affecting follicular fluid epidermal growth factor; growth hormone supplementation significantly decreased follicular fluid androstenedione in both groups.

Insulin-like growth factor-I in human malnutrition: relationship with some body composition and nutritional parameters.

The insulin-like growth factor-I (IGF-I) plasma concentration was evaluated as a nutritional parameter in 18 patients affected with chronic malnutrition secondary to biliopancreatic bypass and compared with albumin, transferrin, and with body composition parameters: total body water (TBW), total body sodium (TBNa), total body potassium (TBK). Subjects were studied in malnutritional conditions and after 20 to 30 days of parenteral and enteral refeeding treatment. Immunoreactive IGF-I concentration was 0.35 U/ml +/- 0.07 (mean +/- SEM), significantly lower (p less than 0.01) than in age-matched controls (1.14 +/- 0.07 U/ml, n = 29) and rose significantly (0.84 +/- 0.12 U/ml; p less than 0.01) in parallel with the improvement of nutritional status. The ratios TBNa/TBW, TBNa/TBK, and TBK/TBW were then considered as reference parameters for definition of malnutritional state, and compared with IGF-I as well as with the most commonly used parameters, albumin and transferrin. Before treatment, IGF-I evidenced higher specificity (true negative ratios 0.63, 0.43, and 0.40 with regard to TBNa/TBW, TBNa/TBK, and TBK/TBW, respectively) than albumin (0.13, 0.14, and 0.10) and transferrin (0 in all cases), and slightly less sensitivity (true positive ratios for IGF-I 0.80, 0.67, and 0.67; always one for albumin and transferrin). Moreover, IGF-I resulted definitely more sensitive in assessing the effectiveness of the refeeding treatment and, on the basis of the likelihood ratio, it appeared a good discriminator of the nutritional status. The data indicate that different nutritional factors regulate IGF-I, albumin, and transferrin, and suggest that IGF-I can be used as a reliable and specific nutritional parameter, complementary to the others currently used.