Influence of sex on chemotherapy efficacy and toxicity in oesophagogastric cancer: A pooled analysis of four randomised trials.

Sex contributes to interpatient variability of chemotherapy metabolism and dose response, potentially influencing both efficacy and toxicity; however, comparative data on its effect on oesophagogastric cancer are lacking. Data for patients with advanced oesophagogastric cancer randomised to comparable first-line chemotherapy regimens within four United Kingdom prospective trials were pooled, and key demographic and outcome measures were compared between males and females. A total of 1654 patients were included: 1328 (80.3%) males and 326 (19.7%) females. Female patients were younger, had a significantly higher proportion of gastric tumours as opposed to junctional or oesophageal tumours and experienced significantly higher rates of a number of toxicities including nausea and vomiting, diarrhoea, stomatitis and alopecia. When adjusting for potential confounding factors, the risk of female patients experiencing grade ≥III gastrointestinal toxicity was greater (adjusted odds ratio = 1.50; 95% confidence interval = 1.07-2.12). Females also had a significantly higher incidence of serious adverse events on treatment and received comparatively less cycles of chemotherapy overall than males. This represents the largest pooled analysis of the effect of sex on chemotherapy outcome and toxicity in advanced oesophagogastric cancer. The differential toxicity and adverse event rates observed suggest that sex may be an important modulator of treatment tolerability and safety in this tumour type