Phase I trial of Idarubicin (4-demethoxydaunorubicin) in adult acute leukemia

Hayat, M.; Hurteloup, P; Parmentier, C; Carde, Patrice; Pico, J; Schlumberger, Martin; Chahine, G.; Kamioner, D.

doi:10.1007/bf00171588

Cited by 17 publications

(4 citation statements)

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“…It is structurally identical to DNR except for a change at position 4 of its chromophore ring conferring a higher lipophilic coefficient, induction of more DNA single-strand breaks in tumor cells, and an active metabolite with a longer halflife as compared with DNR in vitro [Zunino et al 1976;Supino et al 1977;Plumbridge et al 1978;Speth et al 1986]. After phase I testing revealed a myelosuppressive dose-limiting toxicity of 12 mg/ m 2 , phase II studies were performed in Italy, France, and the United States demonstrating that IDR as a single agent induced CR in 13-22% of adult patients with relapsed or refractory AML [Hayat et al 1984;Daghestani et al 1985;Gillies et al 1987]. IDR was combined with cytosine arabinoside (Ara-C) and the response rate increased to the range of 24-70% in similar groups of heavily pretreated patients [Lambertenghi-Deliliers et al 1987;Berman et al 1989].…”

Section: Other Anthracyclinesmentioning

confidence: 99%

Anthracycline dose intensification in young adults with acute myeloid leukemia

Padron¹,

Fernandez²

2011

Therapeutic Advances in Hematology

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Section: Other Anthracyclinesmentioning

confidence: 99%

Anthracycline dose intensification in young adults with acute myeloid leukemia

Padron¹,

Fernandez²

2011

Therapeutic Advances in Hematology

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“…Hematologic toxicity was observed in 3 patients out of 4 treated at 40 rag/m:; at 50 mg/m 2 myelosuppression was prominent and hematological toxicity was observed in all seven patients out of seven at that dose level. d. At the Institute Gustave Roussy, Villejuif, Hayat et al (21) carried out a Phase I trial in eleven adult patients with acute leukemia refractory to prior treatment, using daily i.v. For the platelets the median occurrence of the nadir was on day 13 (range [8][9][10][11][12][13][14][15][16].…”

Section: Distribution and Pharmacokinetics In Animals And Manmentioning

confidence: 99%

“…The median day of nadir was day 12 (range 11-16) with a median WBC nadir of 1.100 (200-1.900). Median duration of leukopenia was 22 days (range [19][20][21][22][23][24][25][26][27][28][29][30]. At the dose of 60 mg/m 2 the median occurrence of recovery was for WBC on day 21 (18)(19)(20)(21)(22)(23)(24) and for platelets on day 25 (22)(23)(24)(25)(26)(27)(28).…”

Section: Distribution and Pharmacokinetics In Animals And Manmentioning

confidence: 99%

Idarubicin (4-demethoxydaunorubicin)

1986

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4-Demethoxydaunorubicin (4-DMDR, IMI 30, Idarubicin, NSC 256439) is a new analog of daunorubicin (DNR) with antileukemic activity in experimental systems that is superior to that of daunorubicin (DNR) or doxorubicin (DX). The drug is more potent than DNR and DX and is active by both the intravenous and the oral routes of administration. After i.v. and oral administration in humans, Idarubicin is rapidly metabolized to its 13-dihydroderivative (Idarubicinol) and the plasma levels of this metabolite are consistently higher than those of the unchanged drug. Idarubicinol has been shown to be an active metabolite in experimental models, being as potent and as active as the parent compound. Phase II clinical trials of Idarubicin have indicated that: By I.V. route Idarubicin is a potent antileukemic agent active in relapsed or refractory, ANLL, ALL (adult and pediatric) either as single agent or in combination with Ara-C at doses of 8-12 mg/m2 by i.v. day 1, 2 and 3 or 7-8 mg/m2 i.v. daily X 5 days (adults). There is evidence of lack of cross-resistance with parent drugs and other antileukemic agents. Phase III studies in previously untreated acute leukemias have been initiated. By oral route Idarubicin has antitumor activity in breast cancer at the doses of 35-45 mg/m2 q 3-4 weeks or 15 mg/m2 daily X 3 days q 3-4 weeks. Idarubicin has activity as a single agent in adult leukemias at the doses of 20-30 mg/m2/day X 3 days. The safety of administration (no risk of extravasation), the good tolerability and the reduced potential for cardiac toxicity, make oral Idarubicin particular attractive for further clinical development. Whether Idarubicin proves to be more effective and/or less cardiotoxic in clinical therapy than DNR or DX remains to be seen through prospective randomized studies which have been already initiated both in leukemias and solid tumors.

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“…Phase-I and early Phase-II trials using intravenous idarubicin have provided evidence of therapeutic activity in acute leukemias [2,4,6], and by oral application in patients with advanced breast cancer [3,5]. The present phase-II trial was designed to gain further information about the efficacy and side-effects of a mono-therapy with oral idarubi cin in patients with measurable advanced breast cancer.…”

Section: Introductionmentioning

confidence: 99%