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Conrad Notes
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F.Cabanillas, MD, University of Texas MD Anderson Cancer Center, Houston, found IDA may improve 3-year survival in >60 year old patients having aggressive poor prognosis non-Hodgkins lymphoma (APPNHL). Replacing Adriamycin® (ADRIA) with low dose IDA in a complex regimen showed less myelosupression and lethal toxicity. Please see US package inserts on idarubicin (Idamycin®) and doxorubicin (Adriamycin®).

Background on IDA and ADRIA As anthracyclines, both drugs produce cytotoxicity by binding to nucleic acids, interfering with nucleotide replication, and by blocking DNA and RNA polymerases. The cytocidal activity may be due to interaction with the enzyme topoisomerase II resulting in DNA-cleavable complexes. IDA is more lipophilic, penetrates cells faster, and is superior to ADRIA in treating acute myeloid leukemia (AML).

Patient selection Cabanillas and coworkers entered 156 APPNHL patients presenting an unfavorable tumor score predictive of a 3-year survival rate of 28% using standard CHOP therapy. (CHOP is the acronym for a regimen of cyclophosphamide, ADRIA, vincristine, and prednisone.) Fifty-two (37%) of the 142 evaluable patients were >60 years old and at increased risk.

In view of the patients' poor prognosis, all received a complex regimen as basic treatment. One group of patients had low-dose IDA instead of ADRIA according to random assignment. The basic regimen, called ATT, consisted of Solu-Medrol®, ADRIA, Ara-C and platinum alternating with m-BACOS (methotrexate, bleomycin, ADRIA, Cytoxan®, vincristine, Solu-Medrol®) and MINE (mesna, ifosfamide, Novantrone® and etopside). Low-dose IDA (2 mg/msq) intravenously for 1 to 3 days replaced regular-dose ADRIA. Subsequent analysis showed both treatment groups to be comparable for age at the beginning and end of evaluation.

IDA substitution helps survival of older patients At the median observation period of 30 months (range, 16-55). Cabanillas and coworkers found the following on >60 year old patients:

Group Pts. %CR %Survival %FFS
IDA 24 68 49 39
ADRIA 28 54 35 27
p value 0.20 0.07 0.17

Low-dose IDA led to a trend for improved survival compared with regular dose ADRIA (p=0.07). Neither % CR (complete remission) nor % FFS (failure-free survival) showed a difference approaching statistical significance (<0.10).

Further analysis of patients at high risk, i.e. those with an International Prognostic Index (IPI) >2, showed significantly better survival in the >60 year old group medicated with IDA. The 3-year rate with substituted IDA was 50%; the original ADRIA rate was 26% (p=0.03). In addition, this patient subset showed a lower lethal toxicity (p=0.03), less myelosuppression (p<0.001), and a higher long-term salvage rate post-relapse, according to Cabanillas and coworkers.

IDA-treated patients did not show an age-related difference in survival (p=0.5). As expected, the 30-month survival rate of the older patient group was significantly lower using standard ADRIA dosing (35% vs 58%) (p=0.01).

Conrad comments Substitution of IDA for ADRIA in the multidrug regimen used in this study complicates interpretation of the results. If feasible, a second investigation using fewer drugs may help uncover the real difference between IDA and ADRIA in APPNHL patients. Regardless, the Cabanillas results provide an important lead for further evaluation of IDA in older non-Hodgkins lymphoma patients requiring highly aggressive treatment.

Eugene A. Conrad

Presented at The American Society of Hematology (ASH) Meeting, December 5-9, 1997
Copyright © 1998 Conrad Group, Inc. All Rights Reserved
Eugene A. Conrad, PhD, MPH / ISSN 1078-2230 / February 1998
Send comments to: ConradNote@aol.com

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