纳米脂质体紫杉醇混悬液与传统紫杉醇治疗转移性乳腺癌患者的多中心、随机、对照、II/III期临床研究

Treatment with nanosomal paclitaxel lipid suspension conventional paclitaxel in metastatic breast cancer patients - a multicenter, randomized, comparative, phase II/III clinical study.

作者信息

Satheesh Chiradoni Thungappa, Taran Rakesh, Singh Jitendra Kumar, Shrivastav Shanti Prakash, Vithalani Nikunj K, Mukherjee Kalyan Kusum, Nagarkar Rajnish Vasant, Maksud Tanveer, Mehta Ajay Omprakash, Srinivasan Krishnan, Vikranth Mummaneni, Sonawane Satish Ramkrishna, Ahmad Ateeq, Sheikh Saifuddin, Ali Shoukath M, Patel Ronak, Paithankar Mahesh, Patel Lav, Rajani Anil, Bunger Deepak, Chaturvedi Alok, Ahmad Imran

机构信息

Sri Venkateshwara Hospital, Bangalore, Karnataka, India.

Convenient Hospital Ltd, CHL-Hospital and CHL-CBCC Cancer Center, Indore, Madhya Pradesh, India.

出版信息

Ther Adv Med Oncol. 2024 Apr 25;16:17588359241236442. doi: 10.1177/17588359241236442. eCollection 2024.

DOI:10.1177/17588359241236442

PMID:38680290

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11047258/

Abstract

BACKGROUND

A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel formulation.

OBJECTIVE

To evaluate the efficacy and safety of NPLS CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC).

DESIGN

A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study.

METHODS

Adult (18-65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m every 3 weeks (Q3W, = 48, arm A), NPLS 80 mg/m every week (QW, = 45, arm B) without premedication or conventional paclitaxel (Taxol, manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m Q3W ( = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A ( = 37) or arm C ( = 17).

RESULTS

Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel [44.4% (20/45) 22.7% (10/44), ( = 0.04)]. An improvement in ORR with NPLS Q3W conventional paclitaxel arm [29.4% (25/85) 22.7% (10/44)] ( = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W conventional paclitaxel Q3W (77.7% 72.7%, = 0.66) and with NPLS QW conventional paclitaxel Q3W (84.4% 72.7%, = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W conventional paclitaxel Q3W arms.

CONCLUSION

NPLS demonstrated an improved tumor response rate and a favorable safety profile conventional paclitaxel. NPLS 80 mg/m QW demonstrated a significantly better response conventional paclitaxel 175 mg/m Q3W.

TRIAL REGISTRATION

Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062).

摘要

背景

开发了一种新型纳米粒紫杉醇脂质混悬液（NPLS），不含聚氧乙烯蓖麻油（CrEL）和乙醇，以解决与传统紫杉醇制剂相关的溶剂相关毒性问题。

目的

评估NPLS与基于CrEL的紫杉醇（传统紫杉醇）在转移性乳腺癌（MBC）患者中的疗效和安全性。

设计

一项前瞻性、开放标签、随机、多剂量、平行的II/III期研究。

方法

既往至少一线化疗失败的成年（18 - 65岁）MBC女性患者被随机分组（2:2:1），分别接受每3周一次（Q3W）的NPLS 175 mg/m²（n = 48，A组）、每周一次（QW）的NPLS 80 mg/m²（n = 45，B组），均无需预处理，或接受每3周一次（Q3W）的传统紫杉醇（泰素，由美国新泽西州普林斯顿的百时美施贵宝公司生产）175 mg/m²（n = 27，C组）并进行预处理。在扩展研究中，另外54例患者被随机分组（2:1）至A组（n = 37）或C组（n = 17）。

结果

来自主要研究及其扩展阶段的汇总数据包括174例患者。主要终点是总缓解率（ORR）。根据意向性分析，与传统紫杉醇相比，NPLS QW组的ORR显著更好[44.4%（20/45）对22.7%（10/44），P = 0.04]。观察到NPLS Q3W组与传统紫杉醇组相比ORR有所改善[29.4%（25/85）对22.7%（10/44）]（P = 0.53）。观察到的疾病控制率在NPLS Q3W组与传统紫杉醇Q3W组（77.7%对72.7%，P = 0.66）以及NPLS QW组与传统紫杉醇Q3W组（84.4%对72.7%，P = 0.20）中有所提高，尽管不显著。NPLS Q3W组与传统紫杉醇Q3W组报告的III/IV级周围感觉神经病变、呕吐和呼吸困难的发生率较低。