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

Feb 9, 2026Journal of thoracic disease

Effectiveness and safety of giving pemetrexed plus platinum chemotherapy at different times of day for advanced lung cancer patients

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Abstract

The morning chemotherapy group experienced a progression-free survival (PFS) of 24.0 months compared to 14.0 months for the afternoon group (P=0.04).

Morning administration of pemetrexed plus platinum chemotherapy is associated with significantly longer progression-free survival in advanced non-small cell lung cancer (NSCLC) compared to afternoon administration.
Subgroup analysis indicates that the morning group consistently showed better PFS across all major patient subgroups.
The rates of treatment-emergent adverse events were similar between morning and afternoon groups, suggesting comparable safety profiles.
However, a higher incidence of grade ≥3 treatment-emergent adverse events was observed in the morning group compared to the afternoon group.
Infusion timing of chemotherapy is identified as an independent prognostic factor for patient outcomes in advanced NSCLC.

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BACKGROUND: Retrospective studies indicate that morning chemotherapy enhances efficacy and reduces side effects in non-small cell lung cancer (NSCLC). However, the role of infusion timing for pemetrexed plus platinum (AP) chronotherapy remains unclear. This study evaluates the impact of AP administration time on efficacy and safety in advanced NSCLC.

METHODS: We retrospectively analyzed 132 advanced NSCLC patients receiving AP chemotherapy at Guangdong Second Provincial General Hospital from 2018 to 2023. Based on previous research, patients were grouped into morning (AM; infusion before 2:00 PM, n=58) and afternoon (PM; n=74) groups. 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 (AEs) were identified and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0.

RESULTS: The AM group showed significantly longer PFS than the PM group (24.014.0 months, P=0.04). 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 (TEAEs) in both AM and PM (AM 86.21%PM 86.49% in AP cohort), and grade ≥3 TEAEs (AM 31.03%PM 21.62% in AP cohort). The most common AEs were anemia, leukopenia, and neutropenia. Univariate and multivariate analyses indicated that the infusion time of AP chemotherapy (P=0.03) was an independent prognostic factor for NSCLC. vs. vs. vs.

CONCLUSIONS: AP treatment administered in the morning may enhance PFS in advanced NSCLC. This suggests that chrono-chemotherapy (CCT) could potentially enhance the efficacy of individualized chemotherapy in advanced NSCLC.