Dataset Information

Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study.

ABSTRACT:

Background

Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC.

Methods

Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.

Results

The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend.

Conclusion

The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8753311 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:PURPOSE:This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS:Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS). RESULTS:Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; P = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% v 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; P = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue (P < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis (P < .05). CONCLUSION:The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.

Project description:BackgroundA recent phase II trial reported prolonged survival in patients with advanced biliary tract cancer (BTC) following treatment with nab-paclitaxel plus gemcitabine-cisplatin (Gem/Cis/nab-P). We aimed to evaluate the clinical outcomes of Gem/Cis/nab-P in Asian patients with advanced BTC in a real-world setting.MethodsWe reviewed the data of patients who received Gem/Cis/nab-P for the management of advanced BTC between September 2019 and April 2021 at four institutes in Korea. Patients were classified into the Gem/Cis/nab-P and nab-P addition groups depending on the starting point of nab-P administration.ResultsA total of 178 patients treated with Gem/Cis/nab-P were included in the study. Of these, 43.8% had intrahepatic cholangiocarcinoma (CCA), 34.8% had extrahepatic CCA, and 21.3% had gall bladder cancer. A total of 117 (65.7%) patients received Gem/Cis/nab-P as the first-line treatment, while 61 (34.3%) were treated with gemcitabine-cisplatin-based chemotherapy followed by nab-P addition. The objective response rate (ORR) and disease control rate in all patients were 42.1% and 84.8%, respectively. The ORR in the Gem/Cis/nab-P group was 47.9%, while that in the nab-P addition group was 31.1%. The median progression-free survival and overall survival were 8.5 months [95% confidence interval (CI), 6.9-10.1] and 14.6 months (95% CI, 10.2-19.0), respectively. In patients who received Gem/Cis/nab-P as initial treatment, the median PFS was 9.4 months (95% CI, 7.9-10.9) and the median OS was not-reached (95% CI, not available). Anemia (n = 42, 23.6%), neutropenia (n = 40, 22.5%), and thrombocytopenia (n = 16, 9.0%) were the most common grade 3-4 toxicities. A total of 20 patients (11.2%) had conversions from unresectable to resectable disease and underwent surgery with curative intent.ConclusionGem/Cis/nab-P showed favorable real-life efficacy and safety outcomes in Korean patients with advanced BTC, which was consistent with the phase II trial outcomes.