BackgroundEnadenotucirev (formerly ColoAd1) is a tumor-selective chimeric adenovirus with demonstrated preclinical activity. This phase 1 Mechanism of Action study assessed intravenous (IV) delivery of enadenotucirev in patients with resectable colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), urothelial cell cancer (UCC), and renal cell cancer (RCC) with a comparator intratumoral (IT) dosed CRC patient cohort.MethodsSeventeen patients scheduled for primary tumor resection were enrolled. IT injection of enadenotucirev (CRC only) was administered as a single dose (≤ 3 × 1011 viral particles [vp]) on day 1, followed by resection during days 8–15. IV infusion of enadenotucirev was administered by three separate doses (1 × 1012 vp) on days 1, 3, and 5, followed by resection during days 8–15 (CRC) or days 10–25 (NSCLC, UCC, and RCC). Enadenotucirev activity was measured using immunohistochemical staining of nuclear viral hexon and quantitative polymerase chain reaction for viral genomic DNA.ResultsDelivery of enadenotucirev was observed in most tumor samples following IV infusion, with little or no demonstrable activity in normal tissue. This virus delivery (by both IV and IT dosing) was accompanied by high local CD8+ cell infiltration in 80% of tested tumor samples, suggesting a potential enadenotucirev-driven immune response. Both methods of enadenotucirev delivery were well tolerated, with no treatment-associated serious adverse events.ConclusionsThis study provides key delivery and feasibility data to support the use of IV infusion of enadenotucirev, or therapeutic transgene-bearing derivatives of it, in clinical trials across a range of epithelial tumors, including the ongoing combination study of enadenotucirev with the checkpoint inhibitor nivolumab. It also provides insights into the potential immune-stimulating properties of enadenotucirev.Trial registrationThis MOA study was a phase 1, multicenter, non-randomized, open-label study to investigate the administration of enadenotucirev in a preoperative setting (ClinicalTrials.gov: NCT02053220).Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-017-0277-7) contains supplementary material, which is available to authorized users.
Introduction There is a growing interest in achieving higher survival rates with the lowest morbidity in localized prostate cancer (PC) treatment. Consequently, minimally invasive techniques such as low-dose rate brachytherapy (BT) and robotic-assisted prostatectomy (RALP) have been developed and improved. Comparative analysis of functional outcomes and quality of life in a prospective series of 51BT and 42Da Vinci prostatectomies DVMaterials and Methods Comparative analysis of functional outcomes and quality of life in a prospective series of 93 patients with low-risk localized PC diagnosed in 2011. 51patients underwent low-dose rate BT and the other 42 patients RALP. IIEF to assess erectile function, ICIQ to evaluate continence and SF36 test to quality of life wee employed.Results ICIQ at the first revision shows significant differences which favour the BT group, 79% present with continence or mild incontinence, whereas in the DV group 45% show these positive results. Differences disappear after 6 months, with 45 patients (89%) presenting with continence or mild incontinence in the BT group vs. 30 (71%) in the DV group. 65% of patients are potent in the first revision following BT and 39% following DV. Such differences are not significant and cannot be observed after 6 months. No significant differences were found in the comparative analysis of quality of life.Conclusions ICIQ after surgery shows significant differences in favour of BT, which disappear after 6 months. Both procedures have a serious impact on erectile function, being even greater in the DV group. Differences between groups disappear after 6 months.
Nivolumab is a fully human immunoglobulin G4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody that selectively blocks the interaction between PD-1, which is expressed on activated T cells, and its ligands PD-L1 and PD-L2, which are expressed on immune cells and tumour cells. Patients with severe renal dysfunction and haemodialysis are not enrolled in clinical trials. However, in daily clinical practice, we have patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD). The scientific evidence about the efficacy and safety of nivolumab in these patients is scarce. We report three cases of mRCC patients with ESRD treated with second-line nivolumab therapy. They received both biweekly and monthly schemes. None of our patients showed grade 2-4 toxicities. Two patients achieved partial response and one progressive disease as best response. Our patients did not show increased toxicity by ESRD; also, two of the three patients had objectifiable clinical benefit. Nivolumab seems to be similarly safe for ESRD or dialysis patients as for patients without impaired kidney function (IKF). Dose adjustments might not be necessary. We suggest that patients on dialysis could be treated with nivolumab in the same way as populations without IKF.
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