Women more likely to experience key side effects from chemotherapy for esophagogastric cancer

MUNICH — Women appeared more likely than men to experience certain side effects from first-line chemotherapy for esophagogastric cancer, according to study results presented at European Society for Medical Oncology Congress.

Sex contributes to variations in dose-response relationships and chemotherapy metabolism between men and women, potentially affecting toxicity and efficacy. However, comparative data on the effect sex has on chemotherapy-related toxicity for first-line treatment of esophagogastric cancer are lacking, according to study background.

“We have known for a long time in oncology that there are differences between males and females in the incidence and prognosis of many nongender-specific cancers,” study author Michael Davidson, clinical research fellow at The Royal Marsden NHS Foundation Trust, said in a press release. “We are now also beginning to understand some of the complex cellular, molecular and metabolic differences between the two sexes which influence both cancer development and response to treatment.

“The clinical question we wanted to answer was whether sex influences the toxicity and efficacy of common chemotherapies administered in esophageal and gastric [cancers],” Davidson added. “It’s the first time that gender-differentiated data has been collected on such a large scale for this tumor type.”

Davidson and colleagues analyzed data pooled from four multicenter randomized controlled clinical trials conducted in the United Kingdom. The trials evaluated different first-line chemotherapy regiments for esophagogastric cancer: epirubicin, cisplatin and fluorouracil (ECF); epirubicin, cisplatin and capecitabine (ECX); epirubicin, oxaliplatin and fluorouracil (EOF); or epirubicin, oxaliplatin and capecitabine (EOX).

Researchers analyzed demographic and outcomes data, then compared prevalence of toxicities between males and females.

The analysis included 1,654 patients (80.3% male). Age and performance status were comparable between males and females. A higher percentage of females had gastric tumors (57.4% vs. 34.1%).

Researchers reported no significant difference in overall rates of common all-grade toxicities and grade 3 or higher toxicities across all four trials between males and females (67.2% vs. 62.8%).

“The data get more interesting once we look at individual toxicity results,” Davidson said in a press release.

Females experienced significantly higher rates of nausea and vomiting (all grade, 89.3% vs. 78.3%; P < .001; grade 3; 16.7% vs. 9.5%; P < .001), diarrhea (all grade, 53.8% vs. 46.9%; P = .027); stomatitis (all grade, 49.5% vs. 40.7%; P = .004) and alopecia (81.4% vs. 74.3%; P = .009).

Researchers also reported trends toward higher rates of grade 3 or higher neutropenia (45.1% vs. 40.4%) and febrile neutropenia (11.8% vs. 7.7%) among females, but the differences did not reach statistical significance.

Males appeared significantly more likely to experience all-grade peripheral neuropathy (49.3% vs. 42.6%; P = .03).

Researchers reported no difference in PFS or OS by sex. A higher percentage of men than women achieved objective response (46.6% vs. 40.4%), but the difference did not reach statistical significance.

Although the results show men and women who underwent similar chemotherapy combinations for esophagogastric cancer were affected to varying degrees by several different toxicities, the clinical relevance of this discovery remains uncertain, Davidson said.

“There is not enough data here to support alternative chemotherapy dosing strategies for men and women, [but] it is useful for clinicians to be aware of such findings in order to refine their treatment in other ways,” Davidson said in the release. “For example, knowing that women are more likely to experience gastrointestinal side effects such as nausea and vomiting or diarrhea may allow for more tailored education to be given to patients, empowering them to report problems early and allowing doctors to introduce supportive measures more proactively and intensively.”

Prior trials have demonstrated differences in treatment reactions between men and women, according to Michel Ducreux, MD, PhD, head of the gastrointestinal unit at Institut Gustav Roussy in Villejuif, France.

“Until recently, though, because no one could explain why such differences might exist, they tended to be written off as a statistical artefact and remained absent from the discussion,” Ducreux, who was not involved with this study, said in the release. “In the clinic, meanwhile, the trends highlighted in this study would have been imperceptible to physicians.

“Thanks to the large number of patients included, this analysis was able to show statistically significant gender differences in the frequency of several side effects of chemotherapy,” Ducreux added. “Now, not only must we discuss their implications, we also need to understand the underlying reasons.”

One option is to stratify patients according to sex in clinical trials to evaluate the efficacy of and tolerance to treatments between sexes from the beginning of drug development.

“If further studies systematically confirm that women are more prone than men to a wider range of side effects, then we will also need to think about entirely different prevention and support strategies for female patients,” Ducreux said. – by Mark Leiser

Reference: Davidson M, et al. Abstract 619PD-PR. Presented at: European Society for Medical Oncology Congress; Oct. 19-23, 2018; Munich.

Disclosure s : The National Institute of Health Research funded this study. Davidson reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.