Dexrazoxane in Patients with B-lymphomas or
Acute Leukemias in the 2nd Complete Remission Enables Further Therapy with Cardiotoxic
Anthracyclines over Recommended Cumulative Doses
Lemež P.1, Stejskal J.1, Cahová S.1, Holub M.2, Svítil P.2, Marešová J.3, Vášová I.4, Boudová L.5, Benešová V.1, Dvořáková D.1, Fišar J.1, Slavíček L.1
1Radioterapeutické oddělení Nemocnice, Jihlava, přednosta prim. MUDr. J. Stejskal 2I. interní oddělení Nemocnice, Jihlava, přednosta prim. MUDr. P. Svítil 3Klinika tuberkulózy a respiračních nemocí Lékařské fakulty UK a FN, Plzeň, přednosta prof. MUDr. M. Pešek, CSc. 4Interní hematoonkologická klinika Lékařské fakulty MU a FN Brno, pracoviště Bohunice, přednosta prof. MUDr. J. Vorlíček, CSc. 5Šiklův patologicko-anatomický ústav Lékařské fakulty UK a FN, Plzeň, přednosta prof. MUDr. M. Michal. |
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Summary:
Daunorubicin (DNR) and doxorubicin (DOX) have significant antitumor activity in acute myeloid
leukemias (AML) and non-Hodgkin’s lymphomas (NHL) but their use is limited by their life-threatening
cumulative dose related cardiotoxicity. It is generally recommended not to administer DOX
or DNR to patients in doses greater than 500 mg/sqm or 700 mg/sqm, respectively. The aim of the
study was to follow up cardiotoxicity and efficacy of DNR or DOX above these limits in the 2nd
complete remission (CR) patients pretreated with anthracyclines when they were given 30 minutes
after cardioprotective agent dexrazoxane (DRZ) in the ratio 1 : 10 of DZR. Results: Two
patients (54 and 53 years old) with mantle cell or diffuse large cell B-NHL, stage IV, who had
relapsed after 6-8 cycles of classical CHOP therapy, reached their 2nd CR after 2 - 3 cycles of IDEA
therapy (ifosfamide 1000 mg/sqm/day x 4, dexamethasone 30 mg/sqm/day x 4, etoposide 75
mg/sqm/day x 4, DOX 30 mg/sqm/day on days 1 and 3). Then they received further 3 cycles IDEA
with DRZ 300 mg/sqm before every dose of DOX. After cumulative doses of DOX 600 mg/sqm and
700 mg/sqm these patients survived 12 months in their 2nd CR without significant signs of cardiotoxicity,
even after their successful autologous peripheral stem cells transplantation. Their left
ventricular ejection fraction (LVEF) remained above 60 %. Six patients with AML in their 2nd CR
were treated with consolidation cycles consisting of 10 high doses of cytosine arabinoside (2000
mg/sqm/12 hr) plus 2 doses of DNR 45 mg/sqm on the day 4 and 5. Two patients received cumulative doses corresponding to 1300 mg/sqm and 1000 mg/sqm of DNR, the other received DNR doses
550 - 850 mg/sqm. No signs of significant cardiotoxicity were observed in all 6 patients and their
LVEF remained over 50 %. One of two patients, transplanted with HLA-identical sibling bone
marrow in her 2nd complete remission (CR), is still 8 years in her 2nd CR. Dexrazoxane enables to
administer anthracyclines in doses over the recommended cumulative ones in pretreated patients
with B-NHL or AML in their 2nd CR with the follow-up of their LVEF.
Key words:
Dexrazoxane - Daunorubicin - Doxorubicin - Mitozantrone - Lymphomas - Acute myeloid
leukemias - Cardioprotection
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