Clin Cancer Res: DNA methyl transferase inhibitor Guadecitabine combined with cisplatin and giscitabine to treat solid malignancies

Preclinical data show that inhibiting DNA methyl transferase can circumvent the resistance of a variety of cancers to cisplatin.
Guadecitabine (SGI-110) is a new type of low-methylated denucleotide on the west coast and an inhibitor of DNA methyl transferase (DNMT).
SPIRE trial is divided into two phases, the first stage is the dose increment phase for incurable metastatic solid cancer, and the second stage is the random dose extension phase for the new auxiliary treatment of bladder urethra cancer in T2-4a phase N0 M0.
the main purpose of the project is to clarify the recommended Phase II dose (RP2D) for guadecitabine in combined giscitabine and cisplatin.
the dose increment phase at the dose increment stage, dose-limiting toxicity is mainly related to the bone marrow inhibition that queue 2 requires G-CSF to prevent (guadecitabine 20 mg/m2, 1-5 days).
The most common ≥ level 3 adverse events in 17 patients during the dose increment phase were a reduction in neutral granulocytes (76.5%), plateplate reduction (64.7%), white blood cell reduction (29.4%) and anemia (29.4%).
the duration of the drug use in the expansion phase, the addition of guadecitabine to Giscitabine and cisplatin can lead to similar rates of severe hematological adverse events, similar to cisplatin dose strength, but a slight decrease in giscitabine dose strength.
options for root-and-drug treatment after chemotherapy have not been compromised.
pharmacodynamic evaluation showed that guadecitabine had the greatest targeting effect at the cisplatin dosing point.
pharmacogenesital dynamics are consistent with previous research data.
no treatment associated with death.
, guadecitabine combined with Giscitabine and Shunplain RP2D is 20 mg/m2 for 1st to 5th days and requires G-CSF to prevent bone marrow inhibition.
although there are some additional bone marrow inhibitions, in general, the addition of guadecitabine on the basis of giscitabine and cisplatin is toned.
further research is needed to assess the efficacy of the joint programme.