[Dexrazoxane in patients with B-lymphomas or acute leukemias in the 2nd complete remission enables further therapy with cardiotoxic anthracyclines over recommended cumulative doses].
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.
Lemez
P
P
Radioterapeutické oddĕlení Nemocnice, Jihlava.
Stejskal
J
J
Cahová
S
S
Holub
M
M
Svítil
P
P
Maresová
J
J
Vásová
I
I
Boudová
L
L
Benesová
V
V
Dvoráková
D
D
Fisar
J
J
Slavícek
L
L
D000208:Acute Disease; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D005260:Female; D006321:Heart; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011929:Razoxane / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002316:Cardiotonic Agents; D011929:Razoxane