Dexrazoxane reduces cardiotoxicity among cancer patients on anthracycline

COCHRANE DATABASE OF SYSTEMATIC REVIEW- INTERVENTION: A third updated review published in the Cochrane Library has highlighted that Dexrazoxane prevents /reduces heart damage in children and adults with cancer receiving anthracycline chemotherapy. The review also focused on antitumor effectiveness (survival and tumor response rate), quality of life, and adverse effects (other than cardiac damage).

Anthracyclines are chemotherapeutic agents used in malignancies, but their dose‐dependent cardiotoxicity limits their use. Cardiotoxicity causes subclinical myocardial dysfunction with subsequent progression to clinical heart failure. Dexrazoxane is cardioprotective and can prevent/reduce cardiotoxicity in such cases. A review was conducted to assess the same in adults and children.

The use of Dexrazoxane was assessed for cardiotoxicity, antitumor efficacy, life quality, and toxicities other than cardiac damage and compared to no additional therapy or placebo. The PICO model of the study included Population(child, adult, infant, middle-aged, young adult, adolescent, cancer, antineoplastic chemotherapy regimen), Intervention (Anthracycline and Dexrazoxane), Comparison(Anthracycline and Placebo) and Outcome (Heart Failure).

The lead researcher was Esmée C de Baat from the Princess Máxima Center for Pediatric Oncology, Netherlands. The study's main question was, "Can Dexrazoxane prevent or reduce heart damage in adults and children with cancer receiving anthracyclines ?

The key points of the study are:

• CENTRAL, MEDLINE, and Embase were searched up to May 2021.

• 548 unique records were identified.

• A total of 13 RCTs (five pediatric, eight adults) were included for analysis by the researchers.

• A total of 1252 enrolled children had leukemia, lymphoma, or a solid tumor.

• 1269 participants had breast cancer.

• Dexrazoxane usage was associated with less clinical heart failure (Risk Ratio, RR: 0.22, 7 studies and 1221 adults). The evidence was of moderate quality.

• No difference in clinical heart failure risk was detected between treatment groups in children. The evidence was low-quality ( RR 0.20, 3 studies, 885 children).

• None of the children had reported cardiomyopathy-related death in three pediatric studies (1008 children, low‐quality evidence).

• Considering adult studies, dexrazoxane usage benefited (moderate‐quality evidence) when different subclinical definitions for myocardial dysfunction and clinical heart failure combined and pooled analyses performed with RR 0.37, 3 studies, 417 adults, and RR 0.46, 2 studies, 534 adults, respectively. This was not possible in pediatric studies.

• One pediatric study showing a benefit in dexrazoxane usage had RR 0.33, 33 children; low‐quality evidence.

• The meta-analysis of Overall survival (OS) in adults (4 studies, moderate quality evidence) and mortality in children (3 studies, 1008 children, low-quality evidence) reported no difference between treatment groups with a hazard ratio (HR) of 1.04 and 1.01, respectively.

• Progression‐free survival (PFS) reported in adults was subdivided into three analyses. One study had longer PFS and favored Dexrazoxane with HR 0.62 (164 adults, low‐quality evidence). The other two analyses (1 study, low-quality evidence, and two studies, moderate‐quality evidence) reported no difference between treatment groups, HR 0.95 and 1.18, respectively.

• Moderate-quality evidence in adults reported no difference in tumor response rate between treatment groups. ( RR 0.91, 6 studies, 956 adults).

• The tumor response rate was subdivided among children into two analyses (based on definition comparability) and identified no difference between treatment groups (RR 1.01, 1 study, 206 children, and RR 0.92, 1 study, 200 children, respectively). The evidence was very low and low-quality for both analyses.

• In children, secondary malignant neoplasms (SMN) occurrence was assessed.

• Children treated with Dexrazoxane are at higher risk of secondary cancers. (unevaluated in adults)

• The quality of life was not evaluated in any of the studies.

The authors finally concluded, "Our meta‐analyses show the efficacy of dexrazoxane to prevent and reduce cardiotoxicity in adults treated with anthracyclines." They added, " In children, there was a difference between treatment groups for one cardiac outcome in favor of dexrazoxane."

There was no recorded negative effect on tumor response rate, OS, and PFS in adults, while in children, there was no evidence of a negative effect on tumor response rate and overall mortality.

Renée L Mulder and the team said, "A higher risk of SMN is related to Dexrazoxane in children; not addressed in adults. The quality of the evidence was between moderate and low in adults and low and very low in children."

It is justifiable to use Dexrazoxane in adults and children on anthracyclines when the risk associated with cardiac damage is expectedly high. It is essential to consider each individual's benefits against the risk (SMN).

Further Reading:

Dexrazoxane for preventing or reducing cardiotoxicity in adults and children with cancer receiving anthracyclines - de Baat, EC - 2022 | Cochrane Library