ArticleJournal of the National Cancer Institute2021
Sex and Adverse Events of Adjuvant Chemotherapy in Colon Cancer: An Analysis of 34 640 Patients in the ACCENT Database.
Article in Journal of the National Cancer Institute, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
54 citing papers in PubMed, 4 syntheses or guidelines pooled it, 81 citations in OpenAlex.
- Sex-based prognosis in industry-sponsored advanced solid tumor trials: an individual participant data meta-analysis of survival and adverse events.Journal of the National Cancer Institute · 2026Pooled it
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- Dihydropyrimidine dehydrogenase gene variants for predicting grade 4-5 fluoropyrimidine-induced toxicity: FUSAFE individual patient data meta-analysis.British journal of cancer · 2024Pooled it
- Symptom Clusters in Head and Neck Cancer: A Systematic Review and Conceptual Model.Seminars in oncology nursing · 2021Pooled it
- Safety and efficacy of PEG-rhG-CSF as primary prophylaxis for neutropenia in gastrointestinal cancer patients receiving combination chemotherapy including oral agents: a prospective, exploratory, non-randomized controlled study.Frontiers in oncology · 2026Trial
- Trial
- Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer.Nature communications · 2022Trial
- Ameliorative Potential of L-Alanyl L-Glutamine Dipeptide in Colon Cancer Patients Receiving Modified FOLFOX-6 Regarding the Incidence of Diarrhea, the Treatment Response, and Patients' Survival: A Randomized Controlled Trial.Medicina (Kaunas, Lithuania) · 2022Trial
- The Preventive Effect of Introducing Glutamine on Chemotherapy-Induced Diarrhea in Colorectal Cancer and Its Influence on Inflammatory Factors Such as CRP and IL-6.Molecular nutrition & food research · 2026Article
- Exploring Risk Factors and Sex Differences in Colorectal Cancer: Insights from Current Evidence.Cells · 2026Review
- Biological Sex Influences the Pharmacokinetics and Organ Dosimetry ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Impact of sex on chemotherapy toxicity and efficacy in biliary tract cancer: Analysis of ABC, BILCAP trials and population data.JHEP reports : innovation in hepatology · 2026Article
- Challenges and Potential Solutions to Advance Global Cancer Drug Development.Therapeutic innovation & regulatory science · 2026Review
- Impact of Physical Frailty on Early Intolerance to CAPOX Chemotherapy in Patients With Colon, Rectal, and Gastric Cancer.Cancer medicine · 2026Observational
- MTHFR polymorphism is associated with increased adverse events and poor clinical outcomes in gastric cancer patients with adjuvant S-1 chemotherapy.Scientific reports · 2026Article
- Effect of sex differences on the emergence of ctDNA RAS mutations in RAS wild-type colorectal cancer.Scientific reports · 2026Article
- Sex impacts inflammatory signaling, body composition, and physical function in tumor-bearing mice receiving chemotherapy.American journal of physiology. Cell physiology · 2026Article
- Association of DPYD rs4294451, plasma uracil concentration, and sex with 5-fluorouracil exposure in patients with gastrointestinal cancer.Cancer chemotherapy and pharmacology · 2025Article
- Sex differences in chemotherapy completion, toxicities, and survival in colon cancer: an analysis of 2201 patients from CALGB/SWOG 80702 (Alliance).Journal of the National Cancer Institute · 2025Article
- Advancements in the diagnosis and management of capecitabine-induced hand-foot syndrome.Journal of cancer research and clinical oncology · 2025Review
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Authors and funding
23 authors at 20 institutions in 6 countries.
Funding
Abstract
backgroundAdjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing.
methodsThe objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin).
resultsData from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk.
conclusionsOur analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation.
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