Lancet oncol: Debio 1143 treats localized advanced head and neck squamous cell carcinoma.

Debio 1143 is an oral apoptosis inhibitor protein antagonist with the potential to enhance anti-tumor activity in cisplatin and radiotherapy.
the radiation allergenic action of Debio 1143 is mediated by cystic winter enzyme activation and TNF, IFN, CD8 T cell dependence pathways.
study was conducted to study the efficacy and safety of Debio 1143 combined standard radiation chemotherapy in patients with high-risk local advanced head and neck squamous cell carcinoma.
This is a double-blind, multicenter, randomized Phase 2 trial that recruited patients with endostatic head and neck squamous cell carcinoma (non-metastatic III, IVa, or IVb) aged 18-75 who had not previously received treatment for immersive head and neck cancer, nor had apoptotic protein inhibitors been used.
randomly assigned patients to Debio 1143 (oral Debio 1143, 200mg/day, 1-14 days) or placebo group, 21 days/course of treatment, with 3 courses.
all patients received standard high-dose cisplatin chemotherapy.
end point was the proportion of patients who had partial control within 18 months of chemotherapy.
January 25, 2016 - April 24, 2017, a total of 96 patients were randomly assigned to two groups (48 each, one patient in the placebo group did not receive the drug under study and was excluded from the safety analysis).
the middle follow-up time in the Debio 1143 and placebo groups was 25 months and 24.2 months, respectively, and the local control rate after 18 months of chemotherapy was 54% and 33%, respectively (advantage ratio of 2.69, 95% CI 1.13-6.42, p.026).
The rates of adverse reactions at level 3 and above were 85% and 87%, respectively, in group
Debio 1143 and placebo groups, with the most common level 3-4 adverse reactions among dysphagic (50% vs 21%), mucositis (31% vs 21%) and anemia (35% vs 23%).
, 30 (48%) and 28 (60%) adverse events requiring urgent treatment were recorded in both groups.
in the placebo group, two (4%) patients died of adverse reactions (1 case of multiple organ failure and 1 case of asphyxiation, both considered unrelated to treatment).
cases of adverse reactions in the experimental group.
it is understood that this is the first randomized trial of this type of disease to obtain a better efficacy than high-dose cisplatin chemotherapy treatment treatment.
the results suggest that inhibition of antioperative protein inhibitors is a promising new treatment for patients with poor prognosis and should be further validated in Phase 3 studies.
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