Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer.

PURPOSE: A phase I trial of intravesical recombinant adenovirus mediated interferon-α2b gene therapy (rAd-IFNα) formulated with the excipient SCH Syn3 was conducted in patients with nonmuscle invasive bladder cancer who had disease recurrence after treatment with bacillus Calmette-Guérin. The primary objective was to determine the safety of rAd-IFNα/Syn3. Secondary end points were demonstrated effective rAd-IFNα gene expression and preliminary evidence of clinical activity at 3 months. MATERIALS AND METHODS: A total of 17 patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment were enrolled in the study. A single treatment of rAd-IFNα (3 × 10(9) to 3 × 10(11) particles per ml) formulated with the excipient Syn3 was administered. Patient safety was evaluated for 12 or more weeks. Efficacy of gene transfer was determined by urine IFNα protein concentrations. Preliminary drug efficacy was determined at 3 months. RESULTS: Intravesical rAd-IFNα/Syn3 was well tolerated as no dose limiting toxicity was encountered. Urgency was the most common adverse event and all cases were grade 1 or 2. rAd-IFNα DNA was not detected in the blood. However, transient low serum IFNα and Syn3 levels were measured. High and prolonged dose related urine IFNα levels were achieved with the initial treatment. Of the 14 patients treated at doses of 10(10) or more particles per ml with detectable urine IFNα, 6 (43%) experienced a complete response at 3 months and 2 remained disease-free at 29.0 and 39.2 months, respectively. CONCLUSIONS: Intravesical rAd-IFNα/Syn3 was well tolerated with no dose limiting toxicity encountered. Dose dependent urinary IFNα concentrations confirmed efficient gene transfer and expression. Intravesical rAd-IFNα/Syn3 demonstrated clinical activity in nonmuscle invasive bladder cancer recurring after bacillus Calmette-Guérin.

Clear cell chondrosarcoma is an underestimated tumor: Report of 7 cases and meta-analysis of the literature.

INTRODUCTION: Clear cell chondrosarcoma (CCC) is a rare subtype of chondrosarcoma and it is commonly considered a low-grade tumor and less aggressive than atypical cartilaginous tumor (grade 1 central chondrosarcoma). However, the experience even of musculoskeletal tumor centres with this rare entity is limited. The aim of this study is to analyse our own treatment results and those of the literature regarding the therapy and outcome of this lesion. MATERIAL AND METHODS: 7 cases of CCC have been treated in our department between 2003 and 2015. Their follow-up data were collected retrospectively. 187 literature cases with histopathological and clinical characteristics were retrieved by means of a PubMed search with the key word "clear cell chondrosarcoma". The data pertaining to treatment and follow up were extracted. We analysed the survival of patient and the risk factors for local recurrence (LR) as well as metastatic disease (MD). RESULTS: The mean age at the time of diagnosis was 40 years. Two thirds of the patients were male. The mean follow-up time was 109 months. To our surprise, there was a high rate of LR (30%) and of MD (20%) when compared to low-grade conventional chondrosarcomas. 15% of LR and 20% of metastatic disease were observed after more than 10 years follow-up. Uncommon locations of MD such as in the spine is a unique observation in chondrosarcomas and underlines the high aggressiveness of this tumor. 10-year overall survival was almost 80%, 10-years disease free survival 60%. Positive margins (p = 0.038) and metastases (p = 0.006) impaired the overall survival significantly. The rate of local recurrence was significantly dependent on resection margin (p < 0.001); however there was no correlation with the grade of differentiation of the tumor. The development of MD was affected by local recurrence (p = 0.006), but we could not detect a significant association with margin status (p = 0.184). CONCLUSIONS: A wide resection is the advocated treatment option. Long term follow-up for at least 10 years is necessary in order to not overlook late LR or MD. This work demonstrates for the first time the apparent aggressiveness of the CCC.