Amsterdam, the Netherlands - Using a longer infusion time for anthracycline administration may reduce the cardiotoxicity of these drugs, suggests a new Cochrane review.

"An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage," the authors conclude.

Anthracycline-induced cardiotoxicity appears to be related to the peak plasma drug concentration, while the antitumor activity depends on tissue concentration over time, lead researcher Dr Elvira van Dalen (Emma Children's Hospital, Amsterdam, the Netherlands) explained. Prolonging the infusion time reduces the peak anthracycline concentration, with potentially less cardiotoxicity, while maintaining the antitumor activity, she said.

The authors conducted a meta-analysis of six randomized clinical trials, involving a total of 625 patients. The majority of patients were adults with different types of solid tumors, and the drugs used were doxorubicin, daunorubicin, and epirubicin.

Results from five trials (n=557) showed that patients who received an infusion over a six-hour period or longer had a significantly lower rate of clinical heart failure than patients who received infusions of shorter duration (lasting one hour or less). The risk was around 75% lower in patients receiving the longer infusions compared with the shorter infusions (relative risk 0.27, 95% CI 0.09-0.81).

Results from two individual trials suggest that the longer infusion time also reduces the risk of subclinical cardiac damage—the various cardiac abnormalities diagnosed with, for example, echocardiography in asymptomatic patients.

The duration of the infusion did not appear to affect either tumor response or overall survival, the researchers report.

The prolonged infusion of six hours or more might be justified in patients who are at high risk of cardiac damage or patients who need a high cumulative dose of chemotherapy, the authors conclude. However, van Dalen added: "Recommendations for clinical practice should be made by clinicians who should weigh all the available evidence, not only on cardiotoxicity but also on antitumor efficacy and other adverse effects."

The researchers emphasize that most of the patients in these studies were adults with advanced solid tumors, and very few children were included. "Since there is only a small amount of data for children and because data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children," they comment.

No adequate studies in children with solid tumors are available, van Dalen noted, although there are two trials in children with leukemia. In these two trials, no difference was seen in the cardiac damage with different infusion durations, and there was no information on antitumor efficacy, she said.

A second Cochrane review by the same group of authors investigated whether the anthracycline derivatives differed in their potential for cardiotoxicity.

There is some suggestion of a lower rate of clinical heart failure with epirubicin compared with doxorubicin, they comment, although the difference was not significant. This analysis was based on five trials involving 1036 patients. "We are not able to favor either epirubicin or doxorubicin when given at the same dose," they conclude.

However, there is evidence to favor liposomal-encapsulated doxorubicin over conventional doxorubicin in adults with solid tumors, they note. In an analysis of two trials involving 521 patients, the liposomal-encapsulated drug was associated with a significantly lower rate of clinical heart failure than the conventional product (RR, 0.20, 95% CI, 0.05-0.75).