Purpose: The chemotherapeutic regimen DCAG (decitabine with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor) is effective for elderly patients with acute myeloid leukemia, but recommendations for young patients remain controversial. This study investigated the tolerance and efficacy of DCAG for patients with newly diagnosed acute myeloid leukemia (aged 14–60 years). The clinical features or molecular markers that may predict response to DCAG were identified.
Patients and methods: One-hundred sixty-one consecutive patients with newly diagnosed acute myelogenous leukemia received DCAG or standard (idarubicin plus cytarabine, IA) induction chemotherapy (n=64 and 97, respectively).
Results: The rates of complete remission after the first cycle, overall survival (OS), and event-free survival (EFS) were comparable. After the second cycle, the complete remission rate of the DCAG group (54.7%) was significantly lower than that of the reference (78.35%, P=0.005). The following were associated with significantly worse OS, and EFS, in the DCAG group: Eastern Cooperative Oncology Group (ECOG) score ≥3 and no response after the second induction therapy; and FLT3-ITD. The multivariate analysis showed the DCAG group with significantly shorter OS associated with ECOG ≥3 and FLT3-ITD. In the DCAG group, after the first cycle of induction chemotherapy the median recovery times of neutrophils and platelets were 15.8 and 13 days.
Conclusion: The DCAG and IA groups were similar with regard to complete remission rate after the first cycle, OS, and EFS. The complete remission rate after the second cycle of the DCAG was significantly lower than that of the IA. Grade 4 neutropenia and thrombocytopenia were a major adverse event associated with DCAG.
Keywords: decitabine, acute myeloid leukemia, induction therapy, conventional chemotherapy
Despite recent progress in leukemogenesis and diagnosis of acute myelogenous leukemia (AML), advances in AML induction chemotherapy treatment are limited. Over the past years, combination chemotherapy with anthracycline and standard dose cytarabine (standard 3+7 induction therapy) remains the standard induction therapy. IA induction chemotherapy (idarubicin plus cytarabine, or, conventional chemotherapy) for AML, results in an overall response rate of about 70%.1–7 Prognosis of patients who are resistant to standard induction chemotherapy is dismal.
The heterogeneity of AML suggests that two-drug 3+7 induction chemotherapy is unlikely to cure all patients, and that combinations of traditional chemotherapy with novel agents will be required to achieve this goal. Recent progress in matching clinical and genomic data may assist in selecting the best-individualized induction therapy for each patient. Emerging evidence indicates that a hypomethylating agent such as decitabine may be effective in certain AML subtypes and selected patients, providing further rationale for a personalized medicine approach. However, clinical data about decitabine in combined induction chemotherapy are limited for the treatment of AML.
Randomized trials of the hypomethylating agent decitabine, used solely to treat patients with newly diagnosed AML, have shown complete response rates of 18–28%, and median overall survival (OS) from 8 to 10 months.7–13 Our research group and others14–16 have combined the chemotherapy regime CAG (ie, low-dose cytarabine [10 mg/m2 q12 hrs for 5 days], aclarubicin hydrochloride [10 mg/day for 5 days], and granulocyte colony-stimulating factor) with decitabine (DCAG). This regimen was designed to exploit the synergy among these agents to improve the proportion of patients achieving response. The overall rate of response (ie, hematologic improvement and partial and complete remission) for elderly AML patients to two cycles of DCAG has been 72.4%. In elderly AML patients, the 2-year disease-free survival and OS were, respectively, 36.9% and 59.6%. However, recommendations regarding DCAG chemotherapy for younger patients with AML have remained controversial.8,17–25
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