紫杉醇聯合抗逆轉錄病毒療法治療愛滋病相關卡波西肉瘤療效顯著
作者：
小柯機器人發布時間：2020/3/10 13:01:00
美國愛滋病惡性聯盟Susan E Krown小組近日取得一項新成果。他們探索了在資源有限的環境中治療晚期愛滋病相關的卡波西肉瘤的有效方案。該研究成果於2020年3月5日發表於《柳葉刀》雜誌上。
目前中低收入國家尚未系統評估與愛滋病相關的卡波西肉瘤的最佳治療方案，雖然該病在這些國家最常見，而卡波西肉瘤常導致愛滋病感染者發病和死亡。
在一項開放性、非劣效性試驗中，研究組在巴西、肯亞、馬拉威、南非、烏幹達和辛巴威的11個愛滋病臨床試驗站點招募晚期愛滋病相關卡波西肉瘤的患者。將其按1：1：1隨機分為3組，在抗逆轉錄病毒治療（ART）的基礎上，隨機接受靜脈注射博來黴素和長春新鹼，或口服依託泊苷（研究組），或靜脈注射紫杉醇（對照組）。
由於研究組的治療劣效性，該試驗提前結束，共有334名患者納入最終分析。治療48周後，紫杉醇+ART組的無進展生存（PFS）率顯著高於兩個研究組，其中與口服依託泊苷+ART組的絕對差值為30%，與博來黴素+長春新鹼+ART組的絕對差值為20%，均超過了非劣效性邊緣。
在329名接受治療的合格參與者中，最常見的不良事件是中性粒細胞減少（15%）、血清白蛋白降低（10%）、體重減輕（9%）和貧血（9%），但各組之間的發生率相差不大。
總之，紫杉醇+ART治療晚期愛滋病相關的卡波西肉瘤，優於口服依託泊苷+ART和博來黴素+長春新鹼+ART，在中低收入國家值得推廣。
附：英文原文
Title: Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial
Author: Susan E Krown, Carlee B Moser, Patrick MacPhail, Roy M Matining, Catherine Godfrey, Stephanie R Caruso, Mina C Hosseinipour, Wadzanai Samaneka, Mulinda Nyirenda, Naftali W Busakhala, Fred M Okuku, Josphat Kosgei, Brenda Hoagland, Noluthando Mwelase, Vincent O Oliver, Henriette Burger, Rosie Mngqibisa, Mostafa Nokta, Thomas B Campbell, Margaret Z Borok, Agnes Moses, Cecilia Kanyama, Pamela Mukwekwerere, Ivy Gudza, Felluna Chauwa, Godwin Ulaya, Irene Kutto, Priscilla Cheruiyot, Clement Okello, Annet Nakaganda, Geoffrey Koskei, Winnie Keter, Juliana Netto, Tamiris Baio, Iveshni Govender, Jessica OConnell-Maritz, Kevin Cain, John Okanda, Lynne Cornelissen, Marije Van Schalkwyk, Rejoice Sikhosana, Minenhle Ngcobo, Jeannette Y. Lee, Taylor Harrison, William Wachsman, Katherine Shin, Scott Evans, Jennifer Rothenberg, Lara Hosey, Sean McCarthy, Otoniel Martinez-Maza, Charles Rinaldo, Dirk Dittmer, Charles Rinaldo, Courtney Fletcher, Michelle Rudek, Aida Asmelash, Valery Hughes, Jeffrey Schouten, David Shugarts, Tapiwanashe Kujinga, Amanda Zadzilka, Fredrick Kerui, Debora Robertson, James Rooney, Krishna Sewal, Brian Gottshall
Issue&Volume: 2020-03-05
Abstract: BackgroundOptimal treatment regimens for AIDS-associated Kaposi sarcoma, a frequent contributor to morbidity and mortality among people with HIV, have not been systematically evaluated in low-income and middle-income countries, where the disease is most common. In this study, we aimed to investigate optimal treatment strategies for advanced stage disease in areas of high prevalence and limited resources.MethodsIn this open-label, non-inferiority trial, we enrolled people with HIV and advanced stage AIDS-associated Kaposi sarcoma attending 11 AIDS Clinical Trials Group sites in Brazil, Kenya, Malawi, South Africa, Uganda, and Zimbabwe. Eligible participants were randomly assigned (1:1:1) with a centralised computer system to receive either intravenous bleomycin and vincristine or oral etoposide (the investigational arms), or intravenous paclitaxel (the control arm), together with antiretroviral therapy (ART; combined efavirenz, tenofovir disoproxil fumarate, and emtricitabine). The primary outcome was progression-free survival (PFS) at week 48, using a 15% non-inferiority margin to compare the investigational groups against the active control group. Safety was assessed in all eligible treated study participants. The study was registered with ClinicalTrials.gov, NCT01435018.Findings334 participants were enrolled between Oct 1, 2013, and March 8, 2018, when the study was closed early due to inferiority of the bleomycin and vincristine plus ART arm, as per the recommendations of the Data and Safety Monitoring Board (DSMB). The etoposide plus ART arm also closed due to inferiority in March, 2016, following a DSMB recommendation. Week-48 PFS rates were higher in the paclitaxel plus ART arm than in both investigational arms. The absolute differences in PFS were 30% (95% CI 52 to 8) for the comparison of paclitaxel plus ART (week 48 PFS 50%, 32 to 67; n=59) and etoposide plus ART (20%, 6 to 33; n=59), and 20% (33% to 7%) for the comparison of paclitaxel plus ART (64%, 55 to 73; n=138) and bleomycin and vincristine plus ART (44%, 35 to 53; n=132). Both CIs overlapped the non-inferiority margin. The most common adverse events, in 329 eligible participants who began treatment, were neutropenia (48 [15%]), low serum albumin (33 [10%]), weight loss (29 [9%]), and anaemia (28 [9%]), occurring at similar frequency across treatment arms.InterpretationNon-inferiority of either investigational intervention was not shown, with paclitaxel plus ART showing superiority to both oral etoposide plus ART and bleomycin and vincristine plus ART, supporting its use in treating advanced AIDS-associated Kaposi sarcoma in resource-limited settings.
DOI: 10.1016/S0140-6736(19)33222-2
Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33222-2/fulltext