Phase Ib/II Study of Safety and Efficacy of Low-dose Decitabine Primed Chemo-immunotherapy in Patients with Drug-resistant Relapsed/Refractory Alimentary Tract Cancer
Mené sur 45 patients atteints d'un cancer digestif réfractaire ou récidivant (cancer de l'œsophage, de l'estomac ou du côlon-rectum), cet essai de phase Ib/II évalue l'efficacité, du point de vue du taux de réponse objective, du taux de contrôle de la maladie, et la toxicité d'une chimio-immunothérapie à base de décitabine à faible dose
The pressing need for improved therapeutic outcomes provides a good rationale for identifying effective strategies for alimentary tract (AT) cancer treatment. The potential re‐sensitivity property to chemo‐ and immunotherapy of low‐dose decitabine has been evident both preclinically and in previous phase I trials. We conducted a phase Ib/II trial evaluating low‐dose decitabine primed chemo‐immunotherapy in patients with drug‐resistant relapsed/refractory esophageal, gastric or colorectal cancers. Forty‐five patients received either the 5‐day decitabine treatment with subsequent re‐administration of the previously resistant chemotherapy (decitabine primed chemotherapy, D‐C cohort) or the aforementioned regimen followed by cytokine‐induced killer cells therapy (decitabine primed chemotherapy and CIK treatment, D‐C+CIK cohort) based on their treatment history. Grade 3 to 4 AEs were reported in 11 (24.4%) of 45 patients. All adverse events (AEs) were controllable, and no patient experienced a treatment‐related death. The objective response rate (ORR) and disease control rate (DCR) were 24.44% and 82.22%, respectively, including 2 patients who achieved durable complete responses. Clinical response could be associated with treatment‐free interval and initial surgical resection history. ORR and DCR reached 28% and 92%, respectively, in the D‐C+CIK cohort. Consistently, the progression‐free survival (PFS) of the D‐C+CIK cohort compared favorably to the best PFS of the pre‐resistant unprimed therapy (p = 0.0001). The toxicity and ORRs exhibited were non‐significantly different between cancer types and treatment cohort. The safety and efficacy of decitabine primed re‐sensitization to chemo‐immunotherapy is attractive and promising. These data warrant further large‐scale evaluation of drug‐resistant relapsed/refractory AT cancer patients with advanced stage disease.