Clin Cancer Res: Decitabine combined with PARP inhibitor tazopanib for refractory/relapsed acute myeloid leukemia

Patients with acute myeloid leukemia (AML) who are ineligible or resistant to intensive chemotherapy are often treated with DNA methyltransferase inhibitors (DNMTi)
.

New drug combination regimens may increase efficacy

leukemia

Maria et al.
have previously demonstrated the combined use of DNMTi and PARPi in AML in vitro and in vivo
.

In the present study, Maria et al.

dose escalation regimen

Patients 18 years of age and older with definitively diagnosed AML that was progressive or refractory to prior therapy and who were intolerant or insensitive to intensive chemotherapy were recruited
.

28 days as a course of treatment, each course of treatment was given decitabine for 5-10 consecutive days, and tazopanib was given on the first day of each course of treatment

diagnosis

A total of 25 patients were recruited, 22 of whom had previously received DNMTi therapy
.

Patients were divided into 7 cohorts in a dose-escalation 3+3 design

non-hematological side effects

Grade 3-5 side effects included fever (19 cases) and pulmonary infection (15 cases)
.

Two patients (8%) achieved complete remission with incomplete recovery of cell counts, and three other patients showed improvement in hematology

Infections Two patients (8%) achieved complete remission with incomplete recovery of cell counts, and three patients had improved haematology Two patients (8%) achieved complete remission with incomplete cell count recovery, and three more patients achieved complete remission with incomplete cell count recovery Patient's hematology improved

Treatment response in all patients

Pharmacodynamic analysis confirmed the expected DNA demethylation, increased chromatin PARP capture, increased γH2AX loci, and decreased HR activity in responders
.

When co-administered with 20 mg/m2 decitabine, the γH2AX site increased with increasing dose of tazopanib

In conclusion, the combination of decitabine/tazopanib is well tolerated in patients with relapsed/refractory AML, and has preliminary antitumor activity , which deserves further study

The combination of decitabine/tazopanib was well tolerated in patients with relapsed/refractory AML, and there was preliminary antitumor activity in patients with relapsed/refractory AML.

Original source:

Maria R.

Phase I Clinical Trial of DNA Methyltransferase Inhibitor Decitabine and PARP Inhibitor Talazoparib Combination Therapy in Relapsed/Refractory Acute Myeloid Leukemia Leave a Comment