In a recent issue of The Lancet Oncology, Hong-Hu Zhu from Peking University People’s Hospital, Beijing, China, published the results of a multicenter, non-inferiority, open-label, randomized, controlled phase III trial (Chinese Clinical Trial Registry number, ChiCTR-TRC-13004054), evaluating the efficacy and safety of oral arsenic realgar-Indigo naturalis formula (RIF) in combination with all-trans retinoic acid (ATRA) compared with intravenous arsenic trioxide (ATO) plus ATRA therapy in patients with newly diagnosed non high-risk acute promyelocytic leukemia (APL).
Between February 2014 and August 2015, 109 patients were enrolled and randomly assigned 2:1 to receive either oral RIF plus ATRA (n = 72) or ATO plus ATRA (n = 37) as induction therapy until complete hematologic remission. As post-remission therapy, RIF or ATO was given on a schedule of 4 weeks’ on and 4 weeks’ off, furthermore, ATRA was administered on a schedule of 2 weeks’ on and 2 weeks’ off for 7 months. The primary endpoint of the study was event-free survival (EFS) at two years. The secondary endpoints included complete remission (CR), overall survival (OS), and safety.
- CR in the RIF-ATRA and ATO-ATRA cohorts: 100% (69/69) vs 94.4% (34/36) respectively, P = 0.12
- 2-year EFS rate in the RIF-ATRA and ATO-ATRA cohorts: 97% vs 94%, P = 0.49
- 2-year overall survival in the RIF-ATRA and ATO-ATRA cohorts: 100% vs 94%, P = 0.049
- There was no significant difference in relapse between the RIF-ATRA and the ATO-ATRA arm, P = 0.32
- Most common grade 3/4 non-hematological and hematological adverse events during induction treatment:
- RIF-ATRA group: neutropenia, anemia, thrombocytopenia, infection, increased liver ALT/AST levels
- Arsenic trioxide-ATRA group: neutropenia, anemia, thrombocytopenia, infection, increased liver ALT/AST levels, hemorrhage
- Liver damage during induction in the RIF-ATRA vs ATO-ATRA arms: 58% vs 78%, P = 0.05
In summary, these results indicate that RIF plus ATRA is not inferior to ATO plus ATRA as first-line treatment of patients with non-high-risk APL. The authors further added that “nonhigh-risk acute promyelocytic leukemia can be cured using complete oral arsenic plus ATRA without conventional chemotherapy. Although longer-term follow-up is needed to draw firm conclusions, our results support previously reported clinical and experimental evidence indicating that ATRA and arsenic act synergistically to eradicate acute promyelocytic leukemia.”