Efficacy and safety of time-of-day infusion of pemetrexed plus platinum for patients with advanced non-small cell lung cancer: A retrospective study

Background: Retrospective studies suggest that administering chemotherapy infusions in the morning can enhance treatment efficacy and mitigate side effects in non-small cell lung cancer (NSCLC) patients. However, the effectiveness of chronotherapy using pemetrexed plus platinum (AP) in advanced NSCLC chemotherapy remains unexplored. This study aims to evaluate the impact of AP chrono-chemotherapy (CCT) on treatment response and adverse events in advanced NSCLC patients. Method: We retrospectively analyzed 132 advanced NSCLC patients treated with AP at Guangdong Second Provincial General Hospital from 2018 to 2023. Based on previous research, we classified patients who received chemotherapy infusions before 2:00 PM as the morning (AM) group, while the rest were categorized as the afternoon (PM) group. Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors Criteria V.1.1. The primary endpoint was progression-free survival (PFS), with safety profile serving as the secondary endpoint. All adverse events were identified and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Result: In the AP cohort, the AM group exhibited a longer PFS compared to the PM group (AM vs. PM, n = 58 vs. n = 74, 24.0 vs. 14.0 months, p = 0.037). Subsequent subgroup analysis in the AP cohort favored the AM group across all major subgroups for PFS treatment effect. Furthermore, the analysis of adverse reactions revealed similar incidences of any treatment emergent adverse events (TEAE) in both AM and PM (AM vs. PM, 86.21% vs. 86.49% in AP cohort), and grade 3 TEAEs (AM vs. PM, 31.03% vs. 21.62% in AP cohort). The most common adverse events were anemia, leukopenia, and Neutropenia. Univariate and multivariate analyses indicated that the infusion time of AP chemotherapy (p = 0.029) was an independent prognostic factor for NSCLC. Conclusion: AP treatment administered in the morning may enhance PFS in advanced NSCLC. This suggests that CCT could potentially enhance the efficacy of individualized chemotherapy in advanced NSCLC.