First-in-Human Study Testing a New Radioenhancer Using Nanoparticles (NBTXR3) Activated by Radiation Therapy in Patients with Locally Advanced Soft Tissue Sarcomas.

Autor:	Bonvalot S; Institut Curie, PSL Research University, Paris, France. sylvie.bonvalot@curie.fr., Le Pechoux C; Gustave Roussy Cancer Campus, Villejuif, France., De Baere T; Gustave Roussy Cancer Campus, Villejuif, France., Kantor G; Institut Bergonié, Bordeaux, France., Buy X; Institut Bergonié, Bordeaux, France., Stoeckle E; Institut Bergonié, Bordeaux, France., Terrier P; Gustave Roussy Cancer Campus, Villejuif, France., Sargos P; Institut Bergonié, Bordeaux, France., Coindre JM; Institut Bergonié, Bordeaux, France., Lassau N; Gustave Roussy Cancer Campus, Villejuif, France., Ait Sarkouh R; Nanobiotix, Paris, France., Dimitriu M; Nanobiotix, Paris, France., Borghi E; Nanobiotix, Paris, France., Levy L; Nanobiotix, Paris, France., Deutsch E; Gustave Roussy Cancer Campus, Villejuif, France., Soria JC; Gustave Roussy Cancer Campus, Villejuif, France.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2017 Feb 15; Vol. 23 (4), pp. 908-917. Date of Electronic Publication: 2016 Oct 06.
DOI:	10.1158/1078-0432.CCR-16-1297
Abstrakt:	Purpose: This phase I study aimed to determine the recommended dose (RD), safety profile, and feasibility of a procedure combining intratumoral injection of hafnium oxide nanoparticles (NBTXR3; a radioenhancer) and external beam radiotherapy (EBRT) for preoperative treatment of adults with locally advanced soft tissue sarcoma (STS). Experimental Design: Patients had a preoperative indication of EBRT for STS of the extremity or trunk. Baseline tumor volume (TV) was calculated by MRI. NBTXR3 was injected percutaneously into tumors at 53.3 g/L. Dose escalation was based on four levels equivalent to 2.5%, 5%, 10%, and 20% of baseline TV. NBTXR3 was visualized in the tumor 24 hours postinjection, and EBRT was initiated (50 Gy over 5 weeks). Surgery was performed 6 to 8 weeks after EBRT completion. Results: Twenty-two patients completed NBTXR3 injection, EBRT, and surgery and were followed for a median 22 months (range, 6-40). At NBTXR3 20% of TV, two dose-limiting toxicities occurred: injection-site pain and postoperative scar necrosis. The RD was defined as 10%. No leakage of NBTXR3 into surrounding tissues occurred; intratumor NBTXR3 levels were maintained during radiotherapy. At the RD, median tumor shrinkage was 40% (range 71% shrinkage, 22% increase); median percentage of residual viable tumor cells was 26% (range, 10%-90%). Patients receiving 20% of TV demonstrated pathologic complete responses. Seven grade 3 adverse events occurred, which were reversible. Conclusions: A single intratumoral injection of NBTXR3 at 10% of TV with preoperative EBRT was technically feasible with manageable toxicity; clinical activity was observed. Clin Cancer Res; 23(4); 908-17. ©2016 AACR . (©2016 American Association for Cancer Research.)
Databáze:	MEDLINE
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