ADVERTISEMENT
Sex differences in chemotherapy-induced toxicities in gastric cancer patients
Background
Female patients have a higher risk for chemotherapy toxicities due to sex differences related to pharmacokinetics and pharmacodinamics. In the era of evolving gender-medicine, sex-adjusted therapies are earning a role and may become a reality. In this study we aim to detect sex differences for toxicities in gastric cancer patients.
Methods
This retrospective analysis included all gastric cancer patients treated with curative intent between january 1st 2017 and december 31st 2021, in a Portuguese hospital. All patients included did a minimum of 5 chemotherapy cycles. Patients with dihydropyrimidine dehydrogenase deficiency were excluded. Data regarding treatment and related toxicity was collected and compared between male and female sex. Toxicities were recorded using Common Terminology Criteria for Adverse Events, version 5. A descriptive analysis was performed using SPSS®, the Mann-Whitney and Chi-square test were used for continuous and categorical variables, respectively.
Results
A total of 72 patients were included, 61,1% were men and 38,9% women with a median age of 66 vs 62 years, respectively (p=0.441) and an ECOG of 0-1. 22 patients did adjuvant chemotherapy preferably with CAPOX regimen (women: 62,5%, men: 64,3%) and 50 patients underwent perioperative chemotherapy mostly with FLOT regimen (women: 75%, men: 83,3%). For grade ≥ 3 reported toxicities, there were no differences between women and men (71,4% vs 59,1%, p=0,288). Higher rates of nausea and vomiting were reported in female sex, both all grade (82,1% vs 52,3%, p=0,015), and grade ≥ 2 (46,4% vs 15,9%, p=0.005). Women experienced more mucositis episodes, both all grade (32,1% vs 11,4%, p=0.034) and grade ≥ 2 (10,7% vs 0%, p=0.027). Other gastrointestinal toxicities such as diarrhea grade ≥ 2 and all grade anorexia were more likely experienced by women (21,4 vs 18,2% and 64,3% vs 45,4%), although statistical significance was not reached. There were no differences in all grade hematologic toxicities, although women tendentially had higher rates of all grade anemia (82,1% vs 59,1%, p=0,120) and neutropenia (42,8% vs 34%, p=0,657), still men experienced more thrombocytopenia (68,2% vs 42,8%, p=0.161). All grade neuropathy was more prevalent in men, particularly with FLOT regimen (92% vs 73,4%, p=0,105). Of all patients, both sexes underwent a median of 8 cycles. The percentage dose of fluoropyrimidine, oxaliplatin and docetaxel administered was lower in women, with results closer to significance with docetaxel (75,3% vs 88%, p=0,058). Women experienced dose reductions more frequently than men (92,9 vs 72,7%, p=0,035), and also dose delays (75% vs 59,1%, p=0,167).
Conclusions
Our results showed that women experience more gastrointestinal toxicities such as nausea/vomiting and mucositis, and tendentially more hematologic toxicities than men. Consequently, dose reductions were significantly more frequent in women, which reinforces the importance of future sex-related interventions in systemic therapy to improve treatment tolerability. Study limitations must be considered such as: its retrospective nature and small sample size, possibly underreported toxicities by clinicians and differences in reporting due to different perceptions of toxicities by both sexes. The consequences of toxicity sex differences must be taken in consideration and its impact in treatment compliance, efficacy and survival further studied.
Legal entity responsible for the study
The author.
Funding
Has not received any funding.
Disclosures
F. Estevinho: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck, MSD, Novartis, Pfizer, Sanofi Genzyme Portugal. All other authors have declared no conflicts of interest.
