Compared with men, women receiving fluorouracil-based chemotherapy for colorectal cancer had higher rates of treatment-emergent adverse events, a retrospective analysis shows.

Women had statistically significant and clinically relevant increased risks of multiple hematologic and nonhematologic toxicities in the analysis, which was based on data from the PETACC-3 trial conducted by the EORTC Gastrointestinal Group.

The findings suggest that drug targets may be different between women and men, as may be the optimal doses needed to hit those targets with acceptable levels of adverse events, said Valerie Cristina, MD, of Lausanne (Switzerland) University Hospital, and her coinvestigators.

“In an age of personalized medicine, and also considering growing knowledge about sex-related differences in molecular profiles and disease biology, the potential effect of sex on efficacy and toxic effects of systemic treatments in oncology deserves more awareness and further investigation,” the researchers wrote. The report was published in JAMA Oncology.

Patients in this retrospective study had stage II-III colorectal cancer and had received treatment with either adjuvant fluorouracil/leucovorin or leucovorin, fluorouracil, and irinotecan (FOLFIRI). Of 2,974 patients, 1,656 (55.7%) were men and 1,318 (44.3%) were women.

The primary analysis in the study was a comparison by sex of treatment-emergent adverse events of any grade. The investigators found women had significantly higher rates of all-grade alopecia, anemia, cholinergic syndrome, constipation, cramping, lethargy, leukopenia, nausea, neutropenia, stomatitis, and vomiting.

Significant differences were reported for hematologic adverse events such as leukopenia of any grade, which was seen in 49.6% of women and 38.9% of men (P less than .001), and nonhematologic adverse events, such as nausea of any grade, seen in 61.8% of women and 53.7% of men (P less than .001).

More serious toxicities (grade 3 or 4) occurring significantly more often in women were alopecia, anemia, diarrhea, leukopenia, nausea, neutropenia, and stomatitis, according to the report.

Treatment with FOLFIRI was associated with higher rates of toxicity overall, and numerically increased differences in incidence between women and men, the investigators said. They noted that incidence of grade 3 or 4 alopecia, diarrhea, lethargy, and stomatitis were all significantly higher among FOLFIRI-treated women.

This was the largest systematic analysis of sex-related differences in adverse effects related to standard fluorouracil with or without irinotecan, according to the researchers, who noted that a previous study had identified female sex as a risk factor for irinotecan-induced neutropenia.

Dr. Cristina had no conflicts of interest to disclose. Coauthors reported disclosures related to Amgen, Bayer, Boehringer, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck, Merck KgA, Novartis, Pfizer, Roche, Sanofi, Servier, and Shire.

SOURCE: Cristina V et al. JAMA Oncol. 2018 May 24. doi: 10.1001/jamaoncol.2018.1080.

In CRC patients, chemo yields more toxicities in women than in men