Trial reportCancer medicine2020
Sex-dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial.
Trial report in Cancer medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Temozolomide Chronotherapy in Glioma: A Systematic Review.Current oncology (Toronto, Ont.) · 2023Pooled it
- Sex-dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial.Cancer medicine · 2020Trial
- Circadian Rhythms in Colorectal Cancer: Recent Advances in Development and Treatment.Journal of clinical medicine research · 2026Review
- Diurnal variation of cisplatin-induced anti-tumor effect and renal toxicity in mice bearing human colon cancer cells.Pharmacological reports : PR · 2026Article
- Article
- Advances in research on circadian rhythms and colorectal cancer.BMC medical genomics · 2026Review
- Metastasis in biological time.Frontiers in cell and developmental biology · 2026Review
- Circadian rhythm in gastrointestinal cancer: clinical applications and future perspectives.Annals of medicine · 2025Review
- Chronotherapy as a novel strategy to limit anthracycline-induced cardiotoxicity.Cardiovascular research · 2025Review
- Nanomaterial-enabled drug delivery systems for circadian medicine: bridging direct rhythm modulation and chronotherapy.RSC advances · 2025Review
- Gender and sex differences in colorectal cancer screening, diagnosis and treatment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Rhythm is essential: Unraveling the relation between the circadian clock and cancer.Critical reviews in oncology/hematology · 2025Review
- Chrono-immunotherapy as a low-hanging fruit for cancer treatment? A call for pragmatic randomized clinical trials.Journal for immunotherapy of cancer · 2025Review
- Why does circadian timing of administration matter for immune checkpoint inhibitors' efficacy?British journal of cancer · 2024Review
- Chronobiology of Cancers in the Liver and Gut.Cancers · 2024Review
- Review
- Chronobiology of the Tumor Microenvironment: Implications for Therapeutic Strategies and Circadian-Based Interventions.Aging and disease · 2024Review
- Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock.NPJ precision oncology · 2024Review
- Circadian Regulation of Endocrine Fibroblast Growth Factors on Systemic Energy Metabolism.Molecular pharmacology · 2024Review
- The Circadian Clock as a Potential Biomarker and Therapeutic Target in Gastrointestinal Cancers.Current pharmaceutical design · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
The least toxic time (LTT) of irinotecan varied by up to 8 hours according to sex and genetic background in mice. The translational relevance was investigated within a randomized trial dataset, where no LTT stood out significantly in the whole population. 130 male and 63 female eligible patients with metastatic colorectal cancer were randomized to receive chronomodulated Irinotecan with peak delivery rate at 1 of 6 clock hours staggered by 4 hours on day 1, then fixed-time chronomodulated Fluorouracil-Leucovorin-Oxaliplatin for 4 days, q3 weeks. The sex-specific circadian characteristics of grade (G) 3-4 toxicities were mapped with cosinor and time*sex interactions confirmed with Fisher's exact test. Baseline characteristics of male or female patients were similar in the six treatment groups. Main grade 3-4 toxicities over six courses were diarrhea (males vs females, 39.2%; vs 46.0%), neutropenia (15.6% vs 15.0%), fatigue (11.5% vs 15.9%), and anorexia (10.0% vs 7.8%). They were reduced following irinotecan peak delivery in the morning for males, but in the afternoon for females, with statistically significant rhythms (P < .05 from cosinor) and sex*timing interactions (Fisher's exact test, diarrhea, P = .023; neutropenia, P = .015; fatigue, P = .062; anorexia, P = .032). Irinotecan timing was most critical for females, with grades 3-4 ranging from 55.2% of the patients (morning) to 29.4% (afternoon) for diarrhea, and from 25.9% (morning) to 0% (afternoon) for neutropenia. The study results support irinotecan administration in the morning for males and in the afternoon for females, in order to minimize adverse events without impairing efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.