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Trifluridine/tipiracil (TAS-102) is an oral chemotherapy approved for the treatment of metastatic colorectal cancer. The efficacy and tolerability of TAS-102 were shown in phase II-III clinical trials and in several real-life studies. The elderly and other special subgroups are underrepresented in published literature. We conducted a retrospective multicenter study to assess the effectiveness and safety of TAS-102 in consecutive patients with pretreated mCRC. In particular, we estimated the effectiveness and safety of TAS-102 in elderly patients (aged ≥70, ≥75 and ≥80 years) and in special subgroups, e.g., patients with concomitant heart disease. One hundred and sixty patients were enrolled. In particular, 71 patients (44%) were 70 years of age or older, 50 (31%) were 75 years of age or older, and 23 (14%) were 80 years of age or older. 19 patients (12%) had a concomitant chronic heart disease, three (2%) patients were HIV positive, and one (<1%) patient had a DPYD gene polymorphism. In 115 (72%) cases TAS-102 was administered as a third-line treatment. The median overall survival (OS) in the overall population was 8 months (95% confidence interval [CI], 6-9), while the median progression-free survival (PFS) was 3 months (95% CI, 3-4). No significant age-related reduction in effectiveness was observed in the subpopulations of elderly patients included. The toxicity profile was acceptable in both the whole and subgroups' population. Our study confirms the effectiveness and safety of TAS-102 in patients with pretreated mCRC, suggesting a similar risk-benefit profile in the elderly.

Background: Pazopanib is an oral multitargeted tyrosine-kinase inhibitor, used as a single agent to treat advanced renal cell carcinoma. Treatment with other tyrosine-kinase inhibitors is known to be associated with asymptomatic elevations of serum amylase and lipase levels. As regards the pazopanib, data are lacking in literature., Case Presentation: We report one case of pancreatic toxicity associated with pazopanib administration. Before starting treatment, patient had no risk factors for pancreatitis. The patient, an Italian 68 years old woman, started pazopanib at doses of 800 mg daily as first-line therapy for metastatic renal cell carcinoma. Six months after the start of treatment, blood tests showed for the first time a significant increase in serum lipase and amylase in the absence of symptoms and radiological findings of pancreatitis. The patient continued treatment without interruptions or dose reductions. However, the continuation of the treatment led to a further increase of pancreatic enzymes. We tried to continue the treatment by reducing the dose but only the discontinuation was associated with normalization of amylase and lipase's levels. On the other hand the treatment with pazopanib got prolonged response of the disease in the absence of signs of pancreatitis. We therefore decided to continue treatment with pazopanib 400 mg daily with close monitoring of blood levels of pancreatic enzymes., Conclusions: We hypothesize that the increase of pancreatic enzymes is not a dose-dependent event. The mechanism for pancreatic toxicity induced by tyrosine-kinase inhibitors is unknown and no predictive factors have been identified. There are no clear guidelines on the management of the drug in the presence of pancreatic enzyme increase. In any case, we believe that a careful monitoring of pancreatic enzymes during treatment with pazopanib is advisable.

Background: Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC., Methods: 177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated., Results: Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis., Conclusion: C+T raise is an early predictor for everolimus efficacy for patients with mRCC.

Purpose: Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC)., Materials and Methods: Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: <1 year, between 1 and 5 years and >5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance., Results: 470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 - 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs., Conclusions: Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.

Sunitinib malate (Sutent; Pfizer, Inc., New York, NY) is an oral multitargeted tyrosine kinase inhibitor that inhibits VEGF receptors (VEGFR-1, VEGFR-2, and VEGFR-3) among a family of kinase targets and have a central role in first-line treatment of metastatic renal cell carcinoma (mRCC). The approved schedule for sunitinib is 50mg/day oid in the so called "4 weeks on and two weeks off" (4/2 schedule). Since treatment with sunitinib can be maintained for years, adequate treatment of adverse events (AEs) and care for quality of life is essential. For this reason, several alternative schedules have been proposed in order to personalize sunitinib administration and reduce related toxicity. This review discusses the efficacy and tolerability of alternative regimens to the standard 4/2 schedule that have been investigated in RCC patients including schedule of 50mg/day 2-weeks on/1-week off, continuous schedule of 37.5mg daily and the "Stop and Go strategy"., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Introduction/background: The purpose of this study was to describe modification of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) distributions in breast cancer patients after aromatase inhibitor (AI) therapy using computed tomography (CT) volumetric measurement of abdominal body fat distribution., Patients and Methods: Sixty-four consecutive patients who were receiving adjuvant AI therapy were included in this study. Patients were evaluated using CT before and after at least 6 months of AI therapy with imaging follow-up of 4.3 ± 2.2 years. Abdominal fat distribution was automatically calculated using a workstation that obtained total abdominal adipose tissue (TAAT) area (mm(3)). SAT was manually segmented and VAT was determined as TAAT - SAT. Percentages were calculated for change of TAAT, VAT, and SAT. VAT/SAT ratio was calculated., Results: Percentage of TAAT after AI therapy was increased by a mean of 9.1% from baseline (16,280.3 ± 6953.3 mm(3)) to (17,763.6 ± 6850.8 mm(3)). Two groups of patients were observed; those with an increase in TAAT and those with a decrease. Modification of VAT/SAT ratio was observed (from 1.38 to 1.69) in all subjects, reflecting a relative increased volume of VAT (mean, 18%) and slight mean reduction of SAT (mean 1.9%)., Conclusion: In our study, therapy with AI in breast cancer patients was accompanied with a change in fat distribution to relatively greater VAT/SAT ratio in patients, regardless of whether they gained or lost weight after therapy. Because this pattern of fat distribution is associated with metabolic disorders, attention must be paid to these clinical manifestations in patients during their follow-up management., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Bone is an uncommon site of metastasis in patients with advanced hepatocellular carcinoma (HCC). Therefore, there are few studies concerning the natural history of bone metastasis in patients with HCC., Patients and Methods: Data on clinicopathology, survival, skeletal-related events (SREs), and bone-directed therapies for 211 deceased HCC patients with evidence of bone metastasis were statistically analyzed., Results: The median age was 70 years; 172 patients were male (81.5%). The median overall survival was 19 months. The median time to the onset of bone metastasis was 13 months (22.2% at HCC diagnosis); 64.9% patients had multiple bone metastases. Spine was the most common site of bone metastasis (59.7%). Most of these lesions were osteolytic (82.4%); 88.5% of them were treated with zoledronic acid. At multivariate analysis, only the Child Score was significantly correlated with a shorter time to diagnosis of bone metastases (p = 0.001, HR = 1.819). The median survival from bone metastasis was 7 months. At multivariate analysis, HCC etiology (p = 0.005), ECOG performance status (p = 0.002) and treatment with bisphosphonate (p = 0.024) were associated with shorter survival after bone disease occurrence. The site of bone metastasis but not the number of bone lesions was associated with the survival from first skeletal related event (SRE) (p = 0.021) and OS (p = 0.001)., Conclusions: This study provides a significant improvement in the understanding the natural history of skeletal disease in HCC patients. An early and appropriate management of these patients is dramatically needed in order to avoid subsequent worsening of their quality of life.

Sunitinib has previously been reported to be potentially effective in the treatment of malignant melanomas expressing c-KIT. Here we report on the case of a 77-year-old gentleman affected by a metastatic clear cell carcinoma of the kidney and a metastatic malignant melanoma with liver and lung metastases. Despite the negativity for CD117 and the absence of KIT amplification or mutations in the melanoma specimen, he achieved a partial response both in the lungs and in the liver while on sunitinib (50 mg once/day, 4 weeks on/2 weeks off) for the treatment of kidney cancer. To our knowledge, this represents the first evidence of sunitinib activity in KIT wild-type melanoma. Further studies should be performed to confirm these preliminary data.

Background: Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs., Methods: In this single-group, prospective study, we consecutively enrolled 45 outpatients with metastatic solid tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome, Rome, Italy, between September, 2010, and November, 2011. We classified patients into two groups: a refactory group, for patients with pruritis refractory to standard treatment, or a naive group, for patients who had not been previously treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day 5) was given to patients in the refractory group after at least 1 week of standard systemic treatment. In the naive group, aprepitant was given in the same schedule as the refractory group, after first onset of severe pruritus. Intensity of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint was change in median VAS score. This trial is registered with ClinicalTrials.gov, number NCT01683552., Findings: Median VAS in the refractory group was 8·00 (95% CI 7·93-8·57) at baseline and 1·00 (0·00-2·00) after 1 week of treatment with aprepitant (p<0·0001). In the naive group, VAS score was 8·00 (7·43-8·37) at baseline and 0·00 (0·06-1·08) after 1 week of treatment (p<0·0001). 41 (91%) patients responded to aprepitant (ie, had a >50% reduction in intensity of pruritis) and pruritus recurred in only six (13%) patients. No adverse events related to aprepitant occurred., Interpretation: Aprepitant decreases severe pruritus induced by biological treatments; it is an old drug, widely available, and therefore easy to add to the armamentarium of supportive treatment. Although to our knowledge no other studies of the anti-itch activity of aprepitant are planned, the results of our trial warrant confirmation in phase 2 and 3 trials., Funding: None., (Copyright © 2012 Elsevier Ltd. All rights reserved.)