From the Journals

Women experience more chemoradiotherapy toxicity in rectal cancer



Women are more likely to experience acute toxic effects from chemoradiotherapy for rectal cancer than men, but this does not appear to negatively impact treatment adherence or outcomes, research suggests.

In a research letter published in JAMA Oncology, Markus Diefenhardt, MD, from the University of Frankfurt and coauthors wrote that, while the risk of toxic chemotherapy effects was known to be greater in women for a number of cancers, this association was relatively unexplored for rectal cancer.

The researchers performed a pooled analysis of data from two phase 3, randomized clinical trials, involving 1,016 patients with rectal cancer – 28.6% of whom were female – treated with fluorouracil-based chemoradiotherapy followed by surgery and adjuvant fluorouracil.

They found that women experienced significantly higher rates of leukopenia and diarrhea than men. Grade 3-4 leukopenia was experienced by 28.6% of women, compared with 20.5% of men, and grades 3-4 diarrhea was experienced by 17.2% of women, compared with 8.1% of men.

Despite this, the study found similar rates of adherence to treatment between men and women both for neoadjuvant and adjuvant chemoradiotherapy. Women also had similar rates of disease-free survival and overall survival as men, and there were no significant differences in local recurrence or distant metastases.

“Although to our knowledge no data support using different chemotherapy regimens for men and women with rectal cancer, increased awareness of a higher risk of toxic effects among women may facilitate refinement of fluorouracil-based chemoradiotherapy and adjuvant chemotherapy, such as tailored patient education, closer monitoring of adverse effects, and earlier introduction of supportive measures,” the authors wrote.

The authors proposed several possible explanations for the higher rate of toxic effects in women. For example, women may have lower levels of the enzyme dihydropyridine dehydrogenase, which catabolizes fluorouracil, which could result in overdosing of fluorouracil. Similarly, sex-specific body fat composition could also contribute to fluorouracil overdosing in women.

The study also saw fewer postoperative complications in women, which the authors suggested could be related to the lower rate of abdominoperineal resections in women.

The two clinical trials included in the study were funded by German Cancer Aid. One author declared funding from German Cancer Aid, another declared a range of honoraria, research fees and institutional funding from the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Diefendhardt M et al. JAMA Oncol. 2019 Dec 5. doi: 10.1001/jamaoncol.2019.5102.

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