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

Autor: Chiradoni Thungappa Satheesh, Rakesh Taran, Jitendra Kumar Singh, Shanti Prakash Shrivastav, Nikunj K. Vithalani, Kalyan Kusum Mukherjee, Rajnish Vasant Nagarkar, Tanveer Maksud, Ajay Omprakash Mehta, Krishnan Srinivasan, Mummaneni Vikranth, Satish Ramkrishna Sonawane, Ateeq Ahmad, Saifuddin Sheikh, Shoukath M. Ali, Ronak Patel, Mahesh Paithankar, Lav Patel, Anil Rajani, Deepak Bunger, Alok Chaturvedi, Imran Ahmad
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Therapeutic Advances in Medical Oncology, Vol 16 (2024)
Druh dokumentu: article
ISSN: 1758-8359
17588359
DOI: 10.1177/17588359241236442
Popis: 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 versus 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 2 every 3 weeks (Q3W, n = 48, arm A), NPLS 80 mg/m 2 every week (QW, n = 45, arm B) without premedication or conventional paclitaxel (Taxol ® , manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m 2 Q3W ( n = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A ( n = 37) or arm C ( n = 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) versus 22.7% (10/44), ( p = 0.04)]. An improvement in ORR with NPLS Q3W versus conventional paclitaxel arm [29.4% (25/85) versus 22.7% (10/44)] ( p = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W versus conventional paclitaxel Q3W (77.7% versus 72.7%, p = 0.66) and with NPLS QW versus conventional paclitaxel Q3W (84.4% versus 72.7%, p = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W versus conventional paclitaxel Q3W arms. Conclusion: NPLS demonstrated an improved tumor response rate and a favorable safety profile versus conventional paclitaxel. NPLS 80 mg/m 2 QW demonstrated a significantly better response versus conventional paclitaxel 175 mg/m 2 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)
Databáze: Directory of Open Access Journals
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