Different administration routes of recombinant human endostatin combined with concurrent chemoradiotherapy might lead to different efficacy and safety profile in unresectable stage III non‐small cell lung cancer: Updated follow‐up results from two phase II trials

Abstract

Background There are two main choices of administration route of recombinant human endostatin (Endostar) available and the treatment options of concurrent chemoradiotherapy (CCRT) have changed over time. The aim of this study was to observe the long‐term efficacy and safety of different administration routes of Endostar combined with CCRT. Methods Patients with unresectable stage III non‐small cell lung cancer (NSCLC) from two phase II trials were included as two cohorts. Both were treated with Endostar combined with CCRT. Endostar was administrated by intravenous injection (7.5 mg/m2/day, seven days) in the IV arm and by continuous intravenous pumping (7.5 mg/m2/24 hours, 120 hours) in the CIV arm. Results A total of 48 patients were included in the IV arm and 67 patients in the CIV arm. The median progression‐free survival (PFS), overall survival (OS), local recurrence‐free survival (LRFS) and distant metastasis‐free survival (DMFS) in the IV arm and CIV arm were 9.9 months versus 15.4 months (HR = 0.751, 95% CI 0.487–1.160, P = 0.200), 24.0 months versus 38.5 months (HR = 0.746, 95% CI 0.473–1.178, P = 0.209), 32.3 months versus 27.1 months (HR = 1.193, 95% CI 0.673–2.115, P = 0.546), 20.1 months versus 49.7 months (HR = 0.603, 95% CI 0.351–1.036, P = 0.067). The one, three, five‐year PFS in the IV arm and CIV arm was 45.8% versus 52.9%, 18.3% versus 31.4%, and 18.3% versus 27.7% and the one, three, five‐year OS was 81.2% versus 82.1%, 31.1% versus 50.3%, and 31.1% versus 41%, respectively. Incidence of hematological adverse reactions were numerically lower in the CIV arm than the IV arm. Conclusions Endostar delivered by CIV with CCRT may be a better option than IV in terms of potential survival and safety for unresectable stage III NSCLC. Key points Significant findings of the study Endostar delivered by continuous intravenous pumping might achieve more favorable survival over intravenous injection and reduce adverse hematological reactions in patients with unresectable stage III NSCLC treated with Endostar combined with CCRT.What this study adds The administration route of recombinant human endostatin is also one key factor for survival and safety to consider when treating patients with unresectable stage III NSCLC.

Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer

“…The use of an infusion pump improved the adherence of patients to rh-endostain treatment. The short-term efficacy and tolerance of Rh-endostain using the above treatment regimen with concurrent radiochemotherapy in unresectable stage Ⅲ NSCLC were satisfactory[ 24 ]. Rh-endostain administered by continuous intravenous infusion using an infusion pump plus concurrent radiochemotherapy was associated with a low incidence of AEs in advanced NSCLC patients.…”

Tumor angiogenesis at baseline identified by 18F-Alfatide II PET/CT may predict survival among patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy

“…Although the safety was tolerable, this strategy did not prolong survival compared with radiotherapy combined with immunotherapy [ 23 ]. Ma et al reported that continuous intravenous infusion of antiangiogenic drugs can significantly improve DFS and OS in patients with unresectable III stage NSCLC compared with intravenous administration of antiangiogenic drugs [ 24 ]. Therefore, the efficacy of antiangiogenic therapy combined with CCRT in patients with unresectable III stage NSCLC based on high RGD PET uptake is worthy of further study.…”

Ameliorating Fibrosis in Murine and Human Tissues with END55, an Endostatin-Derived Fusion Protein Made in Plants

“…These findings suggest that endostatin levels in fibrosis cannot effectively reduce fibrosis, suggesting a “blunted” anti-fibrotic response. Full-length recombinant endostatin, with or without an amino-terminal nonamer, has been studied in the clinical setting for anti-angiogenic properties against various cancers, including gastric, nasopharyngeal, glioblastoma multiforme, lung–brain metastases, and two different lung cancers [ 47 , 48 , 49 , 50 , 51 , 52 ]. Endostatin has also ameliorated bleomycin-induced fibrosis in rats, CCl 4 -induced liver fibrosis in mice, hypertrophic scar formation in rabbit ears, and renal injury in streptozotocin diabetic rats [ 53 , 54 , 55 , 56 , 57 ].…”