Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Therapeutic effect of syringin on adjuvant arthritis in rats and its mechanisms / 药学学报

This study is to investigate the therapeutic effect of syringin on adjuvant arthritis (AA) in rats and its mechanisms. Complete Freund's adjuvant (FCA) was used to induce AA in rats. Secondary paw swelling of AA rats was measured with volume meter. Pain response and polyarthritis index were scored. Meanwhile, splenic lymphocyte proliferation response induced by concanavalin A (ConA) or lipopolysaccharide (LPS) was examined with MTT assay. IL-2 production of splenic lymphocytes and IL-1 beta, TNF-alpha production of peritoneal macrophage (PM phi) were estimated by enzyme linked immunosorbent assay (ELISA). The secondary inflammation of AA rats appeared on the 14th day after injection of FCA. Syringin and tripterygium glycosides (TG) were given by intragastric administration for 16 days from the 14th day. Treatment of AA rats with syringin and TG from the 22th day significantly attenuated the secondary hind paw swelling, as well as relieved the pain response and the polyarthritic symptoms of the whole body as compared with that of the AA model group. The suppressed lymphocyte proliferation and IL-2 production of splenic lymphocytes in AA rats were reversed by treatment with syringin. Meanwhile, syringin remarkably down-regulated IL-1 beta, TNF-alpha productions from PM phi. These results indicate that anti-inflammatory effects of syringin on AA rats are mediated by modulating the immune function of abnormal cells and the balance of cytokines.