Activity and safety of RAD001 (everolimus) in patients affected by biliary tract cancer progressing after prior chemotherapy: a phase II ITMO study.

BACKGROUND: Biliary tract cancer (BTC) is a highly lethal disease for which the best available therapy remains undetermined. The mammalian target of rapamycin (mTOR) pathway is up-regulated in several cancers, including BTC, and preclinical evidence indicates that mTOR inhibition may be effective in the treatment of BTC. We sought to evaluate the activity and tolerability of the mTOR inhibitor RAD001-everolimus-in patients with BTC progressing after prior chemotherapy. PATIENTS AND METHODS: This was an open-label, single-arm, phase II study (EUDRACT 2008-007152-94) conducted in eight sites in Italy. Patients with locally advanced, metastatic or recurrent BTC progressing despite previous chemotherapy received a daily oral dose of everolimus 10 mg administered continuously in 28-day cycles. The two primary end points were disease control rate (DCR) and objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS) and time-to-progression (TTP). RESULTS: Thirty-nine patients were enrolled. The DCR was 44.7%, and the ORR was 5.1%. One patient showed a partial response at 2 months and one patient showed a complete response sustained up to 8 months. The median (95% confidence interval) PFS was 3.2 (1.8-4.0) months, and the median OS was 7.7 (5.5-13.2) months. The median TTP was 2.0 (1.7-3.7) months. Most common toxicities were asthenia (43.6%), thrombocytopenia (35.9%), pyrexia (30.8%) and erythema, mainly of mild-to-moderate severity. Two patients required dose reduction due to adverse events. CONCLUSION: Everolimus demonstrated a favourable toxicity profile and encouraging anti-tumour activity. Further trials are needed to establish the role of everolimus in the treatment of BTC. EUDRACT 2008-007152-94.

Cancer-related fatigue and depression: a monocentric, prospective, cross-sectional study in advanced solid tumors.

BACKGROUND: Cancer-related fatigue (CRF) is common in patients with advanced solid tumors and several risk factors are described. The possible role of depression is reported by clinicians despite the association with CRF being unclear. MATERIAL AND METHODS: In this monocentric, cross-sectional, prospective study we recruited patients with advanced solid tumors who were hospitalized at Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. The primary objective was to assess the correlation between CRF and depression. Secondary objectives were the estimation of CRF and depression prevalence and the identification of associated clinical risk factors. CRF and depression were evaluated through the Functional Assessment of Cancer Therapy-Fatigue subscale and the Zung Self Depression Scale (ZSDS) questionnaires. The Cochran-Armitage trend test was used to demonstrate the primary hypothesis. Univariate and multivariate logistic regression models were used to investigate the impact of clinical variables. RESULTS: A total of 136 patients were enrolled. The primary analysis found a linear correlation (P < 0.0001) between CRF and depression. The prevalence of CRF and of moderate to severe depressive symptoms was 43.5% and 29.2%, respectively. In univariate analysis, patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), anemia, distress, pain, and receiving oncological treatment were at a significantly higher risk for CRF, whereas poor ECOG PS, pain, and distress were risk factors for depression. In multivariate analysis, high levels of ZSDS were confirmed to be correlated to CRF: odds ratio of 3.86 [95% confidence interval (CI) 0.98-15.20) and 11.20 (95% CI 2.35-53.36) for ZSDS of 50-59 and 60-100, respectively (P value for trend 0.002). Moreover, the ECOG PS score was confirmed to be significantly associated with CRF (OR 7.20; 95% CI 1.73-29.96; P = 0.007). CONCLUSIONS: Our data suggest a strong correlation between CRF and depression in patients with advanced solid tumors. Further investigations are needed to better understand this relationship and if depressive disorder therapeutic strategies could also impact on CRF.

Nutritional status and body composition assessment in patients with a new diagnosis of advanced solid tumour: Exploratory comparison of computed tomography and bioelectrical impedance analysis.

OBJECTIVE: Low skeletal muscle is a common characteristic of cancer-related malnutrition and a predictor of poorer prognosis in oncological patients. In this study we evaluated nutritional status and altered body composition using computed tomography (CT) and bioelectrical impedance analysis (BIA) in newly diagnosed patients. Our purpose was to compare the results of two available techniques to assess body composition suggested by the guidelines and some diagnostic criteria to identify malnutrition. METHODS: In a prospective study, patients with a new diagnosis of advanced solid tumour were enrolled and evaluated before starting first-line chemotherapy. Anthropometric, body composition and systemic inflammation measurements were collected and cut-off points from literature data were used for results classification. Malnutrition was expressed as weight loss (WL) in the previous 6 months >10% and underweight body mass index (BMI). Altered body composition was assessed as low index both skeletal muscle (SMI) derived by CT and fat-free mass by BIA (FFMI). Descriptive statistic was presented. Several statistical correlation analyses were performed. RESULTS: 67 patients were assessed: 40M/27F; average age 59 ± 13 years and BMI 23 ± 4; 43 (64%) upper gastrointestinal, 12 lung, 9 colorectal, 3 other cancers. Fourty-five (67%) were malnourished with WL criteria but only 8 (12%) resulted underweight. From analysis of CT images and BIA, 49 (73%) and 10 (15%) patients respectively reported lower cut-off point. Overall, 35 (52%) had both sarcopenia and WL > 10%. CONCLUSIONS: Our results suggest that prevalence data of malnutrition expressed as WL are more in agreement with those of sarcopenia recognised using CT than BIA method. Further studies are required to confirm these findings and to identify the best and easiest methods for monitoring BC during nutritional intervention and oncological therapies.