Background Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression‐free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2. We aim to assess apatinib in patients with advanced high‐grade osteosarcoma progressing upon chemotherapy. Materials and Methods This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. Results A total of 37 participants were finally included into the analysis. Until final follow‐up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4‐month PFS rate was 56.76% (95% confidence interval [CI], 39.43%–70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47–6.27) and 9.87 (95% CI 7.97–18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3–4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar‐plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment‐related deaths. Conclusion Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs. Implications for Practice For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression‐free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second‐line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.
BackgroundResults of our previous study showed high objective response but short-term activity of apatinib in advanced osteosarcoma. We aimed to investigate the activity of apatinib in combination with camrelizumab in patients with inoperable high-grade osteosarcoma progressing after chemotherapy.MethodsThis open-label, phase 2 trial was conducted at Peking University People’s Hospital. We enrolled patients with advanced osteosarcoma progressed after chemotherapy. Patients received 500 mg apatinib orally once daily plus 200 mg camrelizumab by intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS) and clinical benefit rate at 6 months, which were based on RECIST V.1.1.Results43 patients were enrolled between January 25 and September 4, 2018. With median follow-up time of 48.3 (Q1, Q3, 30.6, 66.6) weeks, 13 (30.23%, 95% CI 17.2%, 40.1%) of 43 patients were progression free at 6 months and the 6-month PFS rate was 50.9% (95% CI 34.6%, 65.0%). Until final follow-up, the objective response rate was 20.9% (9/43) and two patients with durable disease control were observed. Patients with programmed cell death 1 ligand-1 (PD-L1) tumor proportion score ≥5% and pulmonary metastases tended to have a longer PFS in comparison to the others (p=0.004 and 0.017, respectively). Toxic effects led to dose reductions, or interruptions, or both in 24 (55.8%) of 43 patients and permanent discontinuation in 4 (9.3%) patients. There were no treatment-related deaths.ConclusionsAlthough the combination of apatinib and camrelizumab seemed to prolong PFS in comparison to single agent apatinib in treating advanced osteosarcoma, it did not reach the prespecified target of 6-month PFS of 60% or greater. Overexpression of PD-L1 and the presence of pulmonary metastases only were associated with longer PFS.Trial registration numberNCT03359018.
Background: Reconstruction with an endoprosthesis following pelvic tumor resection has increased over the years. However, the long-term results reflect a disappointing frequency of mechanical complications and failures. In an attempt to enhance implant fixation, an electron beam melting (EBM)-based modular hemipelvic endoprosthesis was introduced. Our aim was to explore the preliminary clinical outcomes for patients who have been managed with this prosthesis. Methods: We reviewed the records of 80 consecutive patients who had been managed at a single center between June 2015 and September 2017. Chondrosarcoma was the predominant diagnosis (31.3%). Osseous metastases were diagnosed in 16 patients (20.0%). The position of the reconstructed metallic acetabulum was measured on an anteroposterior pelvic radiograph. Bone ingrowth was evaluated in 2 samples harvested from patients with tumor recurrence. Results: After a median duration of follow-up of 32.5 months (range, 9 to 52 months), no acetabular component instability was detected on radiographs. Histological sectioning of specimens harvested from 2 patients with tumor recurrence showed bone trabeculae extending toward the implant and bone ingrowth within the porous network. At the time of the latest follow-up, 59 patients (73.8%) were alive with no evidence of disease, 5 patients (6.3%) were alive with disease, and 16 patients (20.0%) had died of disease. Local recurrence occurred in 9 patients (11.3%). The mean Musculoskeletal Tumor Society score at the time of the latest follow-up was 83.9% (range, 43% to 100%). Complications occurred in 16 patients (20%), with wound dehiscence being the most common complication (8 patients; 10%). No aseptic loosening was found. Five patients (6.3%) had deep infection, and 2 patients (2.5%) had dislocation. Conclusions: The use of a 3-dimensional (3D)-printed modular hemipelvic endoprosthesis with a highly porous metal interface represents a potential choice as a pelvic endoprosthesis after internal hemipelvectomy for the treatment of a primary or metastatic tumor. These preliminary results demonstrate stable fixation with acceptable early functional and radiographic outcomes. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
In developing countries locally-made low-cost prostheses are mainly used in limb-salvage surgery to alleviate the economic burden. We retrospectively collected data on 104 patients treated by limb-salvage surgery between July 1997 and July 2005. We used a locally-designed and fabricated stainless-steel endoprosthesis in each case. Oncological and functional outcomes were evaluated at a mean follow-up of 47 months (12 to 118). A total of 73 patients (70.2%) were free from disease, nine (8.7%) were alive with disease, 19 (18.2%) had died from their disease and three (2.9%) from unrelated causes. According to the Musculoskeletal Tumor Society scoring system, the mean functional score was 76.3% (SD 17.8). The five-year survival for the implant was 70.5%. There were nine cases (8.7%) of infection, seven early and two late, seven (6.7%) of breakage of the prosthesis, three (2.9%) of aseptic loosening and two (1.9%) of failure of the polyethylene bushing. Multivariate analysis showed that a proximal tibial prosthesis and a resection length of 14 cm or more were significant negative prognostic factors. Our survival rates and Musculoskeletal Tumor Society functional scores are similar to those reported in the literature. Although longer follow-up is needed to confirm our results, we believe that a low-cost custom-made endoprosthesis is a cost-effective and reliable reconstructive option for limb salvage in developing countries.
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