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medwireNews: In this round-up, we report on the feasibility of surgery in gastric cancer with limited metastases, the treatment of opioid-induced constipation, monitoring response to immune checkpoint inhibition, and a genetic variant linked to cisplatin-induced ototoxicity.
The German AIO-FLOT3 study, published in JAMA Oncology, suggests that neoadjuvant chemotherapy followed by surgical resection could be a valid option for patients with gastric and gastroesophageal adenocarcinoma with limited metastases.
Median overall survival was 31.3 months for the 36 patients who proceeded to surgery after receiving four cycles of FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel), compared with 15.9 months for the 24 who were not offered surgery, report Salah-Eddin Al-Batran (Institute of Clinical Cancer Research, Frankfurt) and colleagues.
As reported in the Journal of Clinical Oncology, among 225 cancer patients with opioid-induced constipation, a 14-day course of the peripherally acting μ-opioid receptor antagonist naldemedine – at a daily dose of 0.1, 0.2, or 0.4 mg – led to a significant improvement in the frequency of spontaneous bowel movements over placebo.
Nobuyuki Katakami, from the Institute of Biomedical Research and Innovation in Kobe, Japan, and co-researchers recommend the 0.2 mg dose for phase III trials as it “provided the most favorable safety and efficacy profile.”
A proof-of-concept study suggests that quantitative assessment of circulating tumor (ct)DNA levels could help identify patients likely to benefit from anti-programmed cell death protein 1 (PD-1) therapy.
Of 10 nivolumab- or pembrolizumab-treated patients with detectable ctDNA at baseline, radiologic tumor response and survival was significantly better for those who had versus had not cleared ctDNA at week 8, report Francois-Clement Bidard (Institut Curie, Paris, France) and team.
“As inefficient PD-1 blockade could possibly be deleterious, ctDNA monitoring could play a critical role in treatment decisions, especially when the synchronous radiological evaluation is difficult or equivocal,” they write in the Annals of Oncology.
A variant in the SLC16A5 gene – rs4788863 – appears to protect against hearing loss induced by cisplatin in men treated for testicular cancer. Patients carrying the variant had a significant 94% reduced risk for developing ototoxicity, as shown by a combined analysis of the discovery and validation cohorts comprising 96 and 92 men, respectively.
“Given that previous studies have shown that cimetidine, an SLC16A5-inhibitor, prevents murine cisplatin-induced ototoxic effects, the findings from this study have important implications for otoprotectant strategies in humans,” conclude Bruce Carleton (University of British Columbia, Vancouver, Canada) and colleagues in JAMA Oncology.
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