基于中医古籍文献的升降散应用溯源及探析

通过对中医古籍中有关升降散论述的文献梳理,全面探讨其内涵。本方是在大黄、僵蚕为雏形的基础上增加蝉蜕、姜黄而成方,几经易名,终在杨璿《伤寒瘟疫条辨》中为后人所熟知。本方广泛用于治疗瘟疫,以丸剂、散剂为主,方便携带,便于服用;重用大黄旨在祛邪、逐秽;应用时视人之体质强弱和量其毒之轻重而判断用药多寡,并辅以米酒、生蜜等以顾护正气。杨璿将其由治疗“热疫”的专方扩展为治疗“表里三焦大热”的通用方剂,扩大了本方治疗疾病范围。     

Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies

IntroductionPembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.MethodsEligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.ResultsEighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.ConclusionsPembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.