Clinical evaluation of vascular normalization induced by recombinant human endostatin in nasopharyngeal carcinoma via dynamic contrast-enhanced ultrasonography

Abstract

BackgroundThe present study confirmed the presence and exact range of “vascular normalization window” induced by recombinant human endostatin (RHES) in patients with nasopharyngeal carcinoma (NPC) by analyzing the variation of dynamic contrast-enhanced ultrasonography (DCE-US) quantitative parameters. Also, the clinical application of DCE-US in the evaluation of vascular normalization was assessed.Materials and methodsA total of 30 previously untreated patients with stage III–IVA NPC were enrolled in the present study and were randomly but equally divided into RHES (endostar [ES]) and normal saline (NS) groups. The patients in the ES group were administered RHES intravenously, while the patients in the NS group were administered normal saline daily for 5 days prior to intensity modulated radiotherapy coupled with concurrent chemotherapy. All patients underwent DCE-US on the day before the administration and on days 3 and 5 subsequently. The Audio Video Interleave of each DCE-US examination was analyzed quantitatively using the CHI-Q software. Several parameters were investigated, such as peak intensity (PI), time to peak (TTP), and mean transit time (MTT).ResultsThe PI, TTP, and MTT differed significantly at the three time points in the ES group (all P<0.001) but not in the NS group (all P>0.05). In the ES group, PI increased and subsequently decreased, whereas TTP, as well as MTT, lessened initially and then increased within the 5 days after administration of RHES. The maximum value of PI and the minimum value of TTP, as well as MTT, occurred on day 3 (all P<0.05). Furthermore, the values of PI, TTP, and MTT were similar prior to the administration of RHES in both groups (all P>0.05). However, the PI of the ES group was significantly higher (P<0.05), whereas the TTP and the MTT were significantly lower following administration of RHES (all P<0.05) compared with the corresponding parameters of the NS group.ConclusionDCE-US is a suitable method for the clinical evaluation of vascular normalization induced by antiangiogenic agents. The “vascular normalization window” induced by RHES occurs in patients with NPC, and the exact range is within about 5 days post-administration, which contributes towards optimizing the modality of RHES combined with radiotherapy and chemotherapy for NPC patients.

Endostatin Genetically Engineered Placental Mesenchymal Stromal Cells Carrying Doxorubicin-Loaded Mesoporous Silica Nanoparticles for Combined Chemo- and Antiangiogenic Therapy

“…Due to their vascular abnormality, tumors are known to have impaired blood perfusion and offer resistance to chemotherapy [ 7 ]. Endostatin has been used to normalize the aberrant vasculature in tumors [ 52 ] and this effect has even been explored in clinical settings [ 53 ]. In combination with doxorubicin, endostatin has been shown significant tumor and metastasis inhibition in mice 4T1 breast cancer [ 54 ].…”

The performance of pretreatment MR-based radiomics in Recombinant human endostatin plus concurrent chemoradiotherapy response prediction in nasopharyngeal carcinoma: A primary study

“…Since then, scholars have reported through clinical experience and empirical evidence that RHES + radiotherapy and/or chemotherapy has an effect superior to that of a single treatment on various malignant tumors, such as metastatic melanoma and gastric cancer [23,24]. In the clinical treatment of patients with NPC, the RHES + IMRT treatment has also shown good therapeutic effects and good safety [25]. In this study, we focused on 65 patients with NPC having undergone RHES + CCRT, among whom 41 (63.0%) were allocated to the responder group and 24 to the non-responder group.…”

SPECT Imaging of Neovascularization With 99mTc-3PRGD2 for Evaluating Early Response to Endostar Involved Therapies on Pancreatic Cancer Xenografts in Vivo

“…Therefore, new effective therapeutic schemes and sensitive evaluation of curative effect by noninvasive imaging methods become very important. In addition to conventional chemotherapy combinations, multiple trials of anti-angiogenic therapy with anti-VEGF (bevacizumab), anti-VEGFR (sorafenib, Axitinib) or for pancreatic cancer, have been carried out with different results, some producing additional bene ts [41][42][43]and others didn't [16][17][18][19][20][21] with different therapies. In our study, Endostar was chosen as an antiangiogenic drug for the treatment of pancreatic tumors on mouse pancreatic cancer xenografts alone or combined with Gemcitabine .…”

“…They reported that following administration of the antiangiogenic agents, a unique "window" occurred, where irregular vessels inside the tumor were normalized. In recent years, it has been reported that Endostar can not only inhibit neovascularization, but also induce pathological vascular normalization which has shown great clinical potential for enhancing effective drug delivery, improving local immunosuppressive microenvironment, and reducing distant metastasis [51][52]. Therefore, Endostar may be a potential drug for anti-angiogenic therapy of pancreatic cancer.…”