What is the clinical evidence from this study?

Study design: Other. Population: Metastatic cancer (n=8). Intervention: 7-monohydroxyethylrutoside (monoHER) vs. Historical controls (doxorubicin alone). Primary outcome: Histopathological changes in cardiomyocytes (Billingham score) after a cumulative doxorubicin dose of 300 mg/m2.

October 1, 2007Open Access

The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study

ABA. BruynzeelVrije Universiteit Amsterdam HNHans W.M. NiessenHeart Failure & Transplant JBJean G.F. BronzwaerHeart Failure & Transplant

Key Result

MonoHER at 1500 mg/m2 did not protect against doxorubicin-induced cardiotoxicity in patients with metastatic cancer, resulting in a higher mean biopsy score (2.7) than historical controls (1.4).

Structured PICO

Does monoHER prevent doxorubicin-induced cardiotoxicity in patients with metastatic cancer?

Population

8 patients with metastatic solid tumours receiving doxorubicin-based chemotherapy, evaluated for cardioprotection by monoHER.

Intervention

Doxorubicin preceded by a 10 min i.v. infusion of 1500 mg m(-2) 7-monohydroxyethylrutoside (monoHER)

Comparator

Historical data of patients treated with doxorubicin only

Outcome

Histopathological changes in the cardiomyocytes (Billingham score) assessed by endomyocardial biopsy after reaching a cumulative doxorubicin dose of 300 mg m(-2)surrogate

In a small phase II study, high-dose monoHER appeared to enhance rather than prevent doxorubicin-induced cardiotoxicity, while possibly improving antitumour response.

Main Result

Absolute Event Rate: 2.7% vs 1.4%

Limitations

Very small sample size (study stopped early)
Comparison with historical controls rather than a concurrent randomized control group
Biopsies were taken from the left ventricle, whereas historical controls used right ventricle biopsies, potentially overestimating toxicity
Considerable variability in patient sensitivity to the cardiotoxic effects of doxorubicin

Abstract

The purpose of this study was to investigate the cardioprotective effect of the semisynthetic flavonoid 7-monohydroxyethylrutoside (monoHER) on doxorubicin (DOX)-induced cardiotoxicity in a phase II study in patients with metastatic cancer. Eight patients with metastatic cancer were treated with DOX preceded by a 10 min i.v. infusion of 1500 mg m(-2) monoHER. Five patients were examined by endomyocardial biopsy after reaching a cumulative dose of 300 mg m(-2). Histopathological changes in the cardiomyocytes (Billingham score) were compared with those described in literature for patients treated with DOX only. The mean biopsy score of the patients was higher (2.7) than the mean score (1.4) of historical data of patients who received similar cumulative doses of DOX. Although there is a considerable variability in few investigated patients, it was indicative that monoHER enhanced DOX-induced cardiotoxicity. However, the antitumour activity of DOX seemed better than expected: three of the four patients with metastatic soft-tissue sarcoma had a partial remission and the fourth patient stable disease. It is likely that the relatively high dose of monoHER is responsible for the lack of cardioprotection and for the high response rate in patients with soft-tissue sarcoma possibly by depleting the glutathione defense system in both heart and tumour.

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