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Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation.

ABSTRACT: In the treatment of acute myeloid leukemia (AML), the "7?+?3"-based strategy, combining cytarabine 100-200 mg/m2 for 7 days with an anthracycline for 3 days, remains the standard of care for younger and medically fit patients. Daunorubicin (DNR) and idarubicin (IDA) are the two anthracyclines most commonly used. DNR and IDA are used interchangeably with different conversion factors, as there is no high-level evidence on the equipotency of these two agents for AML treatment. To determine the equipotent doses of DNR and IDA, we first systematically reviewed studies directly comparing the clinical outcomes of AML induction therapy utilizing DNR and IDA. We found 15 articles that met our inclusion criteria and compared time-to-event survival end points as well as complete remission rates post-induction. The DNR:IDA equipotency ratio was estimated at 5.90 with 95% confidence interval (CI) 1.7-20.7. To validate the estimate from our meta-analysis biologically, we conducted in vitro tests comparing anti-AML activity of DNR and IDA against six AML cell lines and two primary AML cells from patients with different cytogenetic and molecular characteristics. Based on these in vitro data, the equipotency dose ratio between DNR and IDA was 4.06 with 95% CI 3.64-4.49. Combining the estimates from the meta-analysis and the in vitro data using inverse-variance weighting, the current best estimate of the DNR:IDA equipotent ratio is 4.1 with 95% CI 3.9-4.3. This estimate, however, is largely driven by the in vitro chemo-sensitivity data. Given clinical studies demonstrating the safety of IDA at higher doses, our work implies that dose intensification of IDA could be investigated in future clinical trials in AML.

SUBMITTER: Adige S

PROVIDER: S-EPMC7334867 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Galcanezumab is a novel monoclonal antibody that target to calcitonin gene-related peptide (CGRP). It has been tested for the preventive treatment of migraine and episodic cluster headache by multiple randomized clinical trials (RCTs) and have been found to reduce headache frequency. METHODS:We systematically searched PubMed and Embase on Cochrane Central Register of Controlled Trials (CENTRAL) from the earliest date to August 1, 2019. Relative risk (RR) and weighted mean difference (WMD) were used to evaluate clinical outcomes. RESULTS:Seven studies were pooled with 3889 patients. Subcutaneous injection of Galcanezumab at 120?mg, 240?mg leads to a statistically significant response rate for the treatment of migraine compared with placebo (120?mg: RR?=?1.51; 95% CI, 1.33 to 1.70; P?<?0.001; 240?mg: RR?=?1.58; 95% CI, 1.43 to 1.76; P?<?0.001). Among them, 120?mg group has the same treatment efficacy with 240?mg group (50% response: RR?=?1.06; 95% CI, 0.92 to 1.22; P?=?0.425; 75% response: RR?=?1.07; 95% CI, 0.94 to 1.23; P?=?0.301; 100% response; RR?=?1.06; 95% CI, 0.81 to 1.37; P?=?0.682; MHD: RR?=?-?0.08; 95% CI, -?0.55 to -?0.40; P?=?0.748) while related to a lower risk for adverse events for the treatment of migraine (120?mg RR?=?1.06; 95% CI, 0.99 to 1.14; P?=?0.084; 240?mg: RR?=?1.17; 95% CI, 1.09 to 1.25; P?<?0.001). 300?mg per month galcanezumab is effective for the prevention of episodic cluster headache measured by at least 50% reduction of cluster headache frequency at week 3 (RR?=?1.36; 95% CI, 1.00-1.84; P?=?0.048). CONCLUSIONS:Use of galcanezumab is related to a significantly reduced monthly headache frequency compared with placebo for the treatment of migraine and episodic cluster headache, 120?mg has the same treatment efficacy with 240?mg group while related to a lower risk for adverse effects for the treatment of migraine. 300?mg per month galcanezumab is effective for the prevention of episodic cluster headache with no significantly increased adverse events.

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Equipotent doses of daunorubicin and idarubicin for AML: a meta-analysis of clinical trials versus in vitro estimation.

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