The effect of monohydroxyethylrutoside on doxorubicin-induced cardiotoxicity in patients treated for metastatic cancer in a phase II study.
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.
Bruynzeel
A M E
AM
Department of Medical Oncology, 2 PK BR 010, VU University Medical Center, De Boelelaan 1117, Amsterdam 1081 HV, The Netherlands. ame.bruynzeel@vumc.nl
Niessen
H W M
HW
Bronzwaer
J G F
JG
van der Hoeven
J J M
JJ
Berkhof
J
J
Bast
A
A
van der Vijgh
W J F
WJ
van Groeningen
C J
CJ
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D006896:Hydroxyethylrutoside / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy*
C522803:7-monohydroxyethylrutoside; D000903:Antibiotics, Antineoplastic; D006896:Hydroxyethylrutoside; D004317:Doxorubicin