Phase I study of ADI ‐PEG20 plus low‐dose cytarabine for the treatment of acute myeloid leukemia

Combination of ADI ‐PEG20 at 36 mg/m2 with LDC is tolerable with acceptable toxicities in relapsed/refractory or poor‐risk acute myeloid leukemia and induced an overall response rate of 44.4% and a median overall survival of 8.0 months, The overall response rate and complete remission rate are 71.4% and CR of 57.1 %, respectively, in treatment‐naive patients. This regimen suggests the synergistic effect of the combination of ADI‐PEG20 and chemotherapy and is warranted for further study. AbstractMost acute myeloid leukemia (AML) cells are argininosuccinate synthetase ‐deficient. Pegylated arginine deiminase (ADI‐PEG20) monotherapy depletes circulating arginine, thereby selectively inducing tumor cell death. ADI‐PEG20 was shown to induce complete responses in ~10% of relapsed/refractory or poor‐risk AML patients. We conducted a phase I, dose‐escalation study combining ADI‐PEG20 and low‐dose cytarabine (LDC) in AML patients. Patients received 20 mg LDC subcutaneously twice daily for 10 days every 28 days and ADI‐PEG20 at 18 or 36 mg/m2 (dose levels 1 and 2) intramuscularly weekly. An expansion cohort for the maximal tolerated dose of ADI ‐PEG20 was planned to further estimate the toxicity and preliminary response of this regimen. The primary endpoints were safety and tolerability. The secondary endpoints were time on treatment, overall survival (OS), overall response rate (ORR), and biomarkers (pharmacodynamics and immunogenicity detection). Twenty...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: RESEARCH ARTICLE Source Type: research