Sex is a contributing factor to inter-patient variability of chemo metabolism and dose-response, potentially influencing both efficacy and toxicity. Use of a triplet chemo regimen comprising an anthracycline, platinum and fluoropyrimidine remains a standard option in first line treatment of advanced OG cancer. Comparative data on the effect of sex on chemo-related toxicity in this tumour type are lacking.
Data for pts randomised to ECF, ECX, EOF or EOX chemo within 4 UK-NCRI multicentre RCTs of first line treatment in advanced OG cancer were pooled. Demographic and outcome data, and prevalence of all grade and grade ≥3 toxicity were compared between males and females. Adverse events and response rates were compared by Chi-squared test; survival outcomes by log-rank test.
1654 pts were included; 1328 males (80.3%) and 326 females (19.7%). Age and PS were equally distributed; gastric tumours were more prevalent in females (57.4 vs 34.1%). For toxicities captured commonly across all 4 trials there was no significant difference in all grade or grade ≥3 toxicity between females and males (67.2 vs 62.8%; p=0.19). Females experienced significantly higher rates of nausea and vomiting, both all grade (89.3 vs 78.3%; p<0.001) and grade ≥3 (16.7 vs 9.5%; p<0.001); all grade diarrhoea (53.8 vs 46.9%; p=0.027); all grade stomatitis (49.5 vs 40.7%; p=0.004) and all grade alopecia (81.4 vs 74.3%; p=0.009). There was a trend towards increased rates of grade ≥3 neutropaenia and febrile neutropaenia (45.1 vs 40.4% and 11.8 vs 7.7% respectively), although significance was not reached. Males experienced significantly more all grade peripheral neuropathy (49.3 vs 42.6%; p=0.03). There was no difference in PFS or OS by sex; ORR was higher in males (46.6 vs 40.4%), which approached significance (p=0.051).
This represents the largest pooled analysis of sex effect on outcome and toxicity in advanced OG cancer pts treated with equivalent first line chemo. Females demonstrated significantly higher rates of a number of toxicities, primarily GI in nature, and a trend towards increased rates of neutropaenia. Such results suggest that further research on the impact of sex on the efficacy and toxicity of chemo is necessary.