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ObjectiveTo investigate the clinical efficacy and adverse events (AEs) of apatinib salvage treatment for diffuse malignant peritoneal mesothelioma (DMPM) that has failed to respond to the recommended treatments.Methods27 patients with refractory DMPM were treated with apatinib at our center from April 2014 to October 2020, at the initial dose of 250 mg/d. The dose was reduced to 125 mg/d when serious adverse events (SAEs) occurred. 28-day was set as a treatment cycle. The frequency of follow up was once every 28 days. The efficacy evaluation was conducted according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria and the serum tumor markers before and after apatinib treatment. The safety assessment was performed with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The primary endpoints were objective response rate (ORR) and disease control rate (DCR), and the secondary endpoints were AEs.ResultsThe 27 patients completed a median treatment-cycle of 15.0, ranging from 5.1 to 39.4 cycles. At the median follow-up of 14.3 (4.8-51.8) months, median overall survival (OS) was 59.4 months, median apatinib-treatment-related survival (ATRS) was 14.0 (4.8-36.8) months. Complete response (CR) was observed in 0 case (0.0%), partial response (PR) in 4 cases (14.8%), stable disease (SD) in 12 cases (44.4%), and progression disease (PD) in 11 cases (40.7%). The ORR was 14.8%, and DCR was 59.3%. The median serum CA125 values before and after apatinib treatment were 32.9 (7.0-4592.4) U/mL and 29.7 (6.1-4327.4) U/mL, respectively (P=0.009). The common AEs were hypertension (6/27; 22.2%), hand-foot syndrome (5/27; 18.5%), albuminuria (4/27; 14.8%), anemia (4/27; 14.8%), leukopenia (4/27; 14.8%), rash (2/27; 7.4%), fatigue (2/27; 7.4%), oral ulcers (2/27; 7.4%), hoarseness (2/27; 7.4%), nausea/vomiting (2/27; 7.4%), diarrhea (2/27; 7.4%), headache (1/27; 3.7%), and fever (1/27; 3.7%). The incidence rate of grade III/IV AEs was 16.2%.ConclusionsApatinib is effective in treating refractory DMPM, with promising efficacy and acceptable safety.

ObjectiveMalignant peritoneal mesothelioma (MPM) is a rare malignancy with few effective molecular therapies. In this study, we evaluated the anti-tumor activity and safety of apatinib, a vascular endothelial growth factor receptor 2 inhibitor, in MPM in vitro and in vivo.MethodsWe established several patient-derived xenograft (PDX) models and primary cell lines of MPM. The cell lines were used to study the effects of apatinib on proliferation, cell cycle, migration, and apoptosis by CCK8, flow cytometry, wound-healing, Transwell, DAPI staining, and caspase-3 assays, respectively. For in vivo study, apatinib was delivered by gastric gavage into PDX models, and then efficacy and toxicity were determined by experimental peritoneal cancer index (ePCI) score and pathological examinations.ResultsOur results showed that apatinib significantly inhibited the proliferation and migration of MPM cells in vitro and induced cell cycle arrest. Studies on PDX models concurred that apatinib effectively suppressed subphrenic and liver invasions of nude mice. Moreover, histopathological analysis found that lymphocyte infiltration, coagulation necrosis and eosinophilic cell fragments were detected in tumor tissues after apatinib treatment. Apatinib showed no obvious effects on body mass of models and did not affect function of important organs, except for occasional focal lymphoid infiltration of liver (16.7%) and cardiac muscle (16.7%).ConclusionsWe successfully established MPM PDX models and primary cell lines, and confirmed that apatinib effectively inhibited proliferation and metastasis of MPM in vitro and in vivo study.