Late cardiac toxicity secondary to treatment in Hodgkin's disease. A study comparing doxorubicin, epirubicin and mitoxantrone in combined therapy.
Anthracyclines are a group of drugs that are useful in the treatment of Hodgkin's disease, but have been associated with severe, and in some cases lethal, cardiac toxicity. Apparently, cardiac toxicity is more frequent after 10 years of anthracycline therapy, but no longer studies of cardiac toxicity have been reported. Four hundred and seventy-six patients with Hodgkin's disease, stages III and IV, were randomly assigned to receive ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) compared with EBVD (epirubicin instead of doxorubicin) and MBVD (mitoxantrone instead of doxorubicin) at standard doses. The endpoint was the presence of a clinical cardiac event (CCE) or abnormalities in equilibrium radionuclide angiocardiography (ERNA) and echocardiogram. The patients did not receive radiation therapy and when relapsed they were censored from cardiac toxicity. The median follow-up was 11.5 years (range 7.5 - 14.8 years). CCE was observed in 17% in the MBVD arm, 9% in the ABVD arm and 6% in the EBVD arm (P < 0.001). Mortality associated with CCE was 12% with MBVD, 7% with ABVD and 2% with EBVD. Abnormalities in ERNA and echocardiogram were observed 6 - 36 months before the presence of a CCE. An excess in the standard mortality ratio was observed with the 3 regimens when compared with the general population: 19.4 for EBVD, 46.0 for ABVD and 67.8 for MBVD, which was confirmed with an increase in absolute excess risk/10,000 person-years of 15.6, 39.0 and 58.7, respectively. Overall survival was better in patients treated with EBVD because less cardiac events were observed. The use of mitoxantrone was associated with a high rate of relapse and cardiac events. Thus, we would not recommend use of the drug in Hodgkin's disease. ERNA and echocardiogram are early detection tests for cardiac toxicity and can be employed in surveillance studies.
Avilés
Agustin
A
Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, México, D.F. Mexico. agaviles@avantel.net
Neri
Natividad
N
Nambo
Jesús M
JM
Huerta-Guzman
Judith
J
Talavera
Alejandra
A
Cleto
Sergio
S
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects; D003606:Dacarbazine / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects; D004452:Echocardiography; D015251:Epirubicin / Q000009:adverse effects; D005260:Female; D015637:Gated Blood-Pool Imaging; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000175:diagnosis; D006689:Hodgkin Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000009:adverse effects*; D009367:Neoplasm Staging; D012074:Remission Induction; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects
D001761:Bleomycin; D015251:Epirubicin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin; D008942:Mitoxantrone