Spontaneous regression of bone metastasis from renal cell carcinoma; A case report

BACKGROUND: Spontaneous regression of metastatic renal cell carcinoma is rarely observed. CASE PRESENTATION: Metastatic renal cell carcinoma was identified in a 70-year-old male using computed tomography-guided percutaneous needle biopsy. Two months after the diagnosis, a partial resection of the sternal bone was performed. Pathological examination revealed granulated tissue with bleeding and necrosis but no carcinogenic cells. CONCLUSION: We report a pathologically identified case in which a sternal bone metastasis that was noticed two years after radical nephrectomy regressed completely and spontaneously

Potential limits of AAV-based gene therapy with the use of new transgenes expressing factor IX fusion proteins

Introduction: The variety of treatment for haemophilia B (HB) has recently improved with the emergence of both AAV‐based gene therapy and bioengineered human factor IX (hFIX) molecules with prolonged half‐life due to fusion to either albumin (Alb) or immunoglobulin Fc fragment (Fc). / Aim: Adeno‐associated viral vectors (AAV) mediating expression of hFIX‐Alb and hFIX‐Fc fusion proteins was investigated for gene therapy of HB to explore if their extended half‐life translates to higher plasma levels of FIX. / Methods: Single‐stranded cross‐packaged AAV2/8 vectors expressing hFIX‐Alb, hFIX‐Fc and hFIX were evaluated in vitro, and in mice. / Results: Both hFIX‐Alb and hFIX‐Fc fusion proteins were synthesized and expressed as single chains of expected size following AAV‐mediated gene transfer in vitro and in vivo. The procoagulant properties of these hFIX‐fusion proteins were comparable to wild‐type hFIX. However, their expression levels were threefold lower than wild‐type hFIX in vivo most likely due to inefficient secretion. / Conclusion: This, the first, evaluation of hFIX‐fusion proteins in the context of AAV gene transfer suggests that the hFIX‐fusion proteins are secreted inefficiently from the liver, thus preventing their optimal use in gene therapy approaches

Adjuvant pazopanib does not PROTECT against recurrence of high risk initially localised renal cell cancer, but does provide novel insights

Improved post-surgical management of the 70% of all renal cell cancer (RCC) patients who present to urological surgeons with initially localised RCC, to prevent subsequent progression, is an area of great need within uro-oncology.GD Stewart has received educational grants from Pfizer and Intuitive Surgical; consultancy fees from Pfizer, EUSA Pharma and Cambridge Medical Robotics; Travel expenses from Pfizer and Speaker fees from Pfizer. RA Figlin has received research funding from Peloton, BMS, Argos Therapeutics, Exilexis, and Cerulean; consulting fees from Novartis, Pfizer, Nektar, Peloton, Calithera, and Acceleron. S Negrier reports honoraria from Pfizer, Novartis, EUSA Pharma, Ipsen Biotech and Bristol-Myers Squibb. BC Leibovich declares no conflicts of interest

Metastatic Renal Cell Carcinoma Rapidly Progressive to Sunitinib: What to Do Next?

Background: From 10% to 26% of patients with metastatic renal cell carcinoma (mRCC) experience rapidly progressive disease (PD) on treatment with sunitinib. Objective: To investigate the benefit of subsequent treatment with another tyrosine kinase inhibitor (TKI) or a mammalian target of rapamycin (mTOR) inhibitor in such primary refractory patients. Design, setting, and participants: A total of 150 mRCC patients with rapidly PD on first- line sunitinib (within two cycles, n = 93, or four cycles, n = 57) were identified: median age 59 yr; nephrectomy 86%; histological subtypes: clear cell (77.8%), papillary (14%), and sarco- matoid features (18%); according to the Memorial Sloan-Kettering Cancer Center and French classifications: good risk (11% and 7%, respectively), intermediate (68% and 63%, respectively), and poor (21% and 29%, respectively). Outcome measurements and statistical analysis: Data were retrospectively collected by a questionnaire from 19 European oncology centers between March 2005 and March 2011. Pro- gression-free survival (PFS) and overall survival (OS) were calculated (Kaplan-Meier method). Results and limitations: Median OS from the start of first-line treatment was 7.4 mo. Second-line treatment was administered to 86 (57%) patients (44 mTOR inhibitors: 23 ever- olimus and 21 temsirolimus; 39 TKIs alone or in combination; three chemotherapy). Second- line PFS was not significantly different between TKIs and mTOR inhibitors (2.0 vs 0.9 mo; p = 0.536). Median OS from the start of second-line treatment was 5.0 mo for mTOR inhibitors and 6.6 mo for TKIs (p = 0.15). Conclusions: Treatment with further TKIs or mTOR inhibitors for mRCC patients primarily refractory to first-line sunitinib in the observed time period achieved very minimal benefit, suggesting avoiding TKI rechallenge and possibly preferring alternative strategies, such as immune checkpoint inhibitors, after PD to a treatment line including a TKI in this setting. Patient summary: The present work collected data about 150 patients affected by meta- static renal cell carcinoma, who received one of the current standard of care as first-line treatment, namely, the antiangiogenic drug sunitinib, and experienced rapid worsening of the disease. We investigated and described the subsequent outcome of such patients treated with two different types of drug, administered as second-line therapy, to better understand the best strategy to adopt for patients who got no benefit from sunitinib and to describe the current therapeutic approach in such cases

Basal cytokines profile in metastatic renal cell carcinoma patients treated with subcutaneous IL-2-based therapy compared with that of healthy donors

<p>Abstract</p> <p>Background and purpose</p> <p>Metastatic renal cell carcinoma (MRCC) has a poor prognosis with a median overall survival of about one year. Since only a minority of patients experienced therapeutic benefit to current treatments, several studies have attempted to identify factors that may have an impact on response and survival. Cytokines play a crucial role in the host's immune response by regulating the development and function of a lot of biological compartments. Nevertheless, available data on basal cytokine levels in MRCC are very few and no clear profile of serum cytokines has been identified yet in these patients population. Thus, determining the levels of cytokines in MRCC could not only help in understanding the biological mechanisms of the tumor growth, but also in evaluating if different cytokine profiles are correlated with particular clinical behaviors.</p> <p>Materials and methods</p> <p>In 144 healthy donors and 55 MRCC treated with subcutaneous IL-2-based regimens, we analysed a panel of basal cytokines particularly involved in the neoplastic progression (IL-1beta, IL-6, IL-8, IL-10, IL-12, alpha-TNF) and C-reactive protein (CRP) in order to compare their levels in the two groups, and to verify their impact on patient response and survival.</p> <p>We first compared cytokines levels in patients population and healthy donors. Than, in definite patients group, univariate and multivariate analyses were performed to evaluate the correlation existing between each factor considered and clinical outcomes. For these analyses, baseline values were included as dichotomous variables using the median values (above and below) of control group.</p> <p>Results</p> <p>In general, higher levels of cytokines were found in patients with respect to those of healthy donors, both in term of percentage of undetectable levels or median values. The impact on response was insignificant, except for higher levels of CRP that were strongly correlated with a worse response (p < 0.001). Within the patients groups, a worse survival was associated with higher values of CRP (8 vs 31 months, p = 0.0000), IL-6 (9 vs 25 months, p = 0.0295), and IL-8 (9 vs 17 months, p = 0.0371). Conversely, higher levels of IL-12 were associated with a better survival (25 vs 15 months, months p = 0.0882). A correlation was found between CRP and IL-6 (p = 0.009) and between CRP and IL-10 (p = 0.038). After multivariate analysis only CRP (p = 0.0035) and IL-12 (p = 0.0371) maintained an independent impact on survival, while IL-6 showed a borderline value (p = 0.0792).</p> <p>Conclusion</p> <p>Higher cytokines levels characterize patients population with respect to healthy donors. Moreover, higher basal level of some immunosuppressive cytokines (CRP, IL-6, IL-8) result correlated with a poorer survival, whereas higher levels of IL-12, a cytokine with a potent antineoplastic activity, was associated with a better survival. A wider sample of patients is needed to better clarify if our findings are intrinsically related to patients population or if they are simply an epiphenomenon of disease progression.</p

Hepatic intra-arterial versus intravenous fotemustine in patients with liver metastases from uveal melanoma (EORTC 18021): a multicentric randomized trial

Despite an improved antitumor efficacy as noticed by an enhanced response rate and an improved progression-free survival, the hepatic intra-arterial fotemustine did not increase the overall survival of uveal melanoma patients with liver metastases only. We propose to consider intrahepatic treatment as an experimental approac

How clinical practice is changing the rules: the sunitinib 2/1 schedule in metastatic renal cell carcinoma.

Introduction Currently, sunitinib is a standard of care in first-line treatment for metastatic renal cell carcinoma (mRCC). However, with the standard 4/2 schedule (sunitinib 50 mg/day; 4 consecutive weeks on treatment; 2 weeks' rest), 50% of patients require dose reductions to mitigate toxicity, highlighting the need to investigate alternative dosing schedules that improve tolerability without compromising efficacy. Areas covered: We present a concise critical review of published studies comparing the efficacy and safety of the 4/2 and 2/1 schedule (2 weeks on treatment; 1 week rest) for sunitinib. While all studies evaluating the 2/1 schedule have a low level of evidence, the results indicate that the 2/1 schedule improves tolerability compared with the 4/2 schedule, including significant reductions in the incidence of specific adverse events. It was not possible to make any definitive conclusions regarding efficacy due to methodologic limitations of these studies. Expert commentary: In the absence of strong evidence supporting the safety and efficacy of the 2/1 schedule, we recommend that patients should be initiated on sunitinib therapy with the standard 4/2 schedule and only be switched to the 2/1 schedule after the development of dose-limiting toxicities from weeks 3-4 (cycle 1) of the 4/2 schedule cycle