Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia

Kaminer, L.; Choi, Kyung Jun; Daley, Karen M.; Larson, Richard A.

doi:10.1002/1097-0142(19900615)65:12<2619::aid-cncr2820651203>3.0.co;2-i

Cited by 9 publications

(4 citation statements)

References 4 publications

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“…The incidence when equivalent doses were used was 0.9% for mitozantrone and 3.1% for doxorubicin, and the maximum cumulative dose which eave a 5% risk of congestive cardiac failure was found to be 160 mg/m 2 20 . A phase I study with continuous infusion of an escalating dose of mitozantrone to an optimum dose of 1.1 mg/m 2 /day for 21 days, and a recent study of continuous infusion over a five‐day period in acute non‐lymphocytic leukaemia showed no significant cardiotoxicity 21 , 22 …”

Section: Preclinical Activitymentioning

confidence: 99%

An Overview of Mitozantrone

Birchall

Bailey

Blackledge

1991

Int J Clinical Practice

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INTRODUCTION Mitozantrone is a member of the anthraquinone group of chemicals. Anthraquinones were used as blue dyes in the fabric industry in the early 20th century, and subsequently in ballpoint pen ink as ametantrone.1 Since the discovery of doxorubicin in 1968 searches have continued for anthracycline‐related compounds with improved efficacy and/or a different spectrum of activity with less toxicity.

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Section: Preclinical Activitymentioning

confidence: 99%

An Overview of Mitozantrone

Birchall

Bailey

Blackledge

1991

Int J Clinical Practice

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“…17 In patients with relapsed AML, CI-MTZ therapy resulted in rapid clearance of leukemic blasts from the bone marrow with 98% reduction in leukemic cell mass on the 6th day of the regimen. 18 In the early pharmacokinetic studies in humans, demonstration of the persistence of MTZ in various tissues for up to 9 months in relation to the lifetime cumulative dose of MTZ is suggestive of a possible negative effect on late relapses in patients with AML. 19 The efficacy and toxicity of CI-MTZ have not yet been studied in patients with newly diagnosed AML.…”

Section: Introductionmentioning

confidence: 99%

“…In the light of the previously published pharmacokinetic and clinical data, 17,18 we conducted a randomized study to evaluate the effect of mode of administration of MTZ on the response and recurrence rates in newly diagnosed patients with AML. Toxicity patterns associated with bolus and CI administration of MTZ throughout the treatment period were also compared.…”

Section: Introductionmentioning

confidence: 99%

A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia

Koç

Oyan

Kars

et al. 2004

Hematological Oncology

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SUMMARYMitoxantrone (MTZ) has been shown to be effective in the treatment of newly diagnosed acute myeloblastic leukemia (AML). The objective of this randomized study was to evaluate the impact of mode of administration of MTZ on the response and recurrence rates in newly diagnosed patients with AML and to compare the toxicity patterns associated with bolus and continuous infusion (CI) of MTZ. From March 1987 to March 1994, 40 newly diagnosed patients with AML were randomized to receive either bolus or CI-MTZ, administered for 3 days at 10 mg/m 2 /day in combination with CI-cytarabine for 7 days at 100 mg/m 2 /day. Patients achieving complete remission (CR) received two consolidation cycles followed by monthly maintenance cycles, aiming a total of 12 cycles of chemotherapy. Fifteen patients (75%) in the bolus arm and 16 patients (80%) in the CI arm achieved CR. There were no significant differences in rates of early death and time to myeloid recovery between the two groups. After 11 years from the initiation of the study, median disease-free survival (DFS) in bolus and CI groups were 19 and 29 months after a median follow-up of 10 and 14 months, respectively. DFS rates at 10 years were 16.7% in the bolus group and 28.6% in the CI group ( p ¼ 0.36). Overall survival (OS) rates during the same period were 10.7 and 21.3% in the bolus and CI groups, respectively ( p ¼ 0.26). No relapse was observed in either group after 4 years. In patients younger than 40 years of age, DFS and OS were found to be significantly longer in the CI arm ( p ¼ 0.02 and p ¼ 0.03, respectively). Mild asymptomatic cardiotoxicity associated with a decrease of 10 to 20% in the ejection fraction occurred in a patient in CI-MTZ arm and in two patients in the bolus arm. None of these patients showed any evidence of cardiac failure during their subsequent follow-up. Grade III-IV alopecia ( p ¼ 0.05) and grade I-II hepatotoxicity ( p ¼ 0.01) were more frequent in the CI arm. A tendency for higher frequency of grade III-IV nausea was observed in the bolus arm (9 vs. 3%, p ¼ 0.10). As a conclusion, bolus and CI administration of MTZ were equally effective and tolerated well. Development of new anti-leukemia agents with novel treatment approaches is still needed to improve the high relapse rates in patients with AML who do not have an HLA-matched donor.

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“…Several alternative antileukemic therapy choices have become available [3,4] and have proved their ability to produce remissions in patients who have failed to enter remission after two cycles of treatment based in daunorubicin or doxorubicin [5]. None has been incontrovertibly shown to be better than the traditional regimens in initial induction [6], but several-most notably high-dose Ara-C 171 and mitoxantrone/etoposide-have become favored over a third cycle of the starting regimen and have become popular for the re-induction therapy of patients who have relapsed [8].…”

Section: Introductionmentioning

confidence: 99%

Anthracycline‐based therapy of de novo acute myeloid leukemia in adults: Failure of first‐cyde cytoreduction to predict second‐cycle outcome

Hammerschmidt

Crea

1994

American J Hematol

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During 1971-1988, 194 adults with de novo acute myeloid leukemia (AML) received initial therapy at the University of Minnesota with an anthracycline-based regimen. Seventy-two of the 194 required further chemotherapy and received a second cycle of the same or similar therapy; 63 of these 72 were evaluable. For each marrow, a tumor burden index (TBI) was calculated, as the product of the marrow cellularity and the proportion of malignant cells. For each patient, the decrement in TBI between the initial and day approximately 14 marrows was recorded. Patients who achieved second-cycle CR were comparable to those who did not in general descriptors; there was no difference between second-cycle CR achievers and nonachievers in the cytoreduction effected by the initial cycle of therapy (74.9% +/- 4.5% [sigma] versus 71.9% +/- 5.9%). We then stratified patients according to the first-cycle cytoreduction, asking if we could find a level that was reliably predictive of increased or decreased likelihood of achieving CR with cycle 2. We could not, despite testing at many centile cuts. Patients achieving a very "poor" degree of cytoreduction in cycle 1 were as likely to achieve CR with cycle 2 as were patients having a very "good" initial cytoreduction. We conclude that (1) first-cycle response is not a useful predictor of second-cycle outcome in anthracycline-based therapy of de novo adult AML; and (2) a "poor" response to cycle 1 does not therefore a priori indicate a change to a different regimen for cycle 2.

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Continuous infusion mitoxantrone in relapsed acute nonlymphocytic leukemia

Cited by 9 publications

References 4 publications

An Overview of Mitozantrone

An Overview of Mitozantrone

A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia

Anthracycline‐based therapy of de novo acute myeloid leukemia in adults: Failure of first‐cyde cytoreduction to predict second‐cycle outcome

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