Phase I trial of 4-demethoxydaunorubicin with single i.v. doses

Kaplan, S.; Martini, A.; Varini, M.; Togni, P.; Cavalli, F.

doi:10.1016/0277-5379(82)90133-x

Cited by 29 publications

(9 citation statements)

References 3 publications

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“…The major toxicity observed in this trial was myelosuppression with leukopenia being more significant than thrombocytopenia. This is consistent with the observations of other investigators, both after intravenous and oral administrations (7)(8)(9)(10)(11). In the schedule that was selected initially (4 administrations for 4 consecutive weeks), the maximum tolerated dose appears to be 20 mg/m 2.…”

Section: Discussionsupporting

confidence: 82%

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Phase I study of oral idarubicin given with a weekly schedule

Dodion¹,

Finet²,

Crespeigne³

et al. 1986

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Thirty one patients with solid tumors were entered into a phase I trial with idarubicin, a new anthracycline antibiotic with oral antitumor activity in animals. The drug was scheduled to be given for 4 consecutive weeks at doses ranging from 10 to 20 mg/m2. Leukopenia was the dose-limiting toxicity. Thrombocytopenia was occasionally seen. Since several patients could not receive the third and fourth administrations of the drug at 17.5 and 20 mg/m2, higher doses were administered only for 2 consecutive weeks. With this schedule, the maximum tolerated dose was 25 mg/m2 and leukopenia was again the dose-limiting toxicity. With both schedules, myelosuppression was highly variable and could not be related to prior therapy, bone or liver metastases, or performance status. Other toxicities were mild to moderate and were dominated by nausea and vomiting which were observed in 29% of the patients. Alopecia and mucositis were unfrequent and cardiac toxicity was not observed. Starting doses of 15 mg/m2 for 4 consecutive weeks or 20 mg/m2 for 2 consecutive weeks could be proposed for oral phase II studies with idarubicin, under careful pharmacokinetic monitoring.

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Section: Discussionsupporting

confidence: 82%

“…Several phase I studies with idarubicin have already been reported (7)(8)(9)(10). In all these studies, leukopenia was the dose-limiting toxicity.…”

Section: Introductionmentioning

confidence: 97%

Phase I study of oral idarubicin given with a weekly schedule

Dodion¹,

Finet²,

Crespeigne³

et al. 1986

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“…formulation has already been publish-* Presented in part at the Third NCI-EORTC Symposium on New Drugs in Cancer Therapy, Brussels, October 13-17, 1981. Address for reprints: F. Cavalli, M.D., Division of Oncology, Ospedale San Giovanni, 6500 Bellinzona, Switzerland. ed (6). These studies were undertaken as part of the new drug program of the Early Clinical Trials Group of the EORTC.…”

Section: Introductionmentioning

confidence: 99%

Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses

et al. 1984

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Twenty-four patients with a variety of solid tumors entered a Phase I trial with 4-demethoxydaunorubicin, a new analogue of daunorubicin. The drug was given as a single oral dose of 10-60 mg/m2 repeated every 3-4 weeks. Leukopenia was the dose-limiting toxicity. Other toxic effects included mild to moderate nausea and vomiting. Sixty mg/m2 was found to be the maximum tolerated dose in patients with fair tolerance to chemotherapy and normal liver function. Similar hematologic toxicity was reported in patients with very extensive prior chemotherapy or diffuse bone and/or liver metastases receiving 50 mg/m2. However, the wide range of the WBC nadirs reported with the same dose in 'good risk' cases, suggest that 40 mg/m2, increased up to 50 mg/m2 in the absence of significant myelotoxicity, could be more safely proposed as starting dose for Phase II trials. Pharmacokinetic studies were performed in five patients given a single dose of 40-60 mg/m2. IMI-30 (NSC 256439) appears to be rapidly absorbed and rapidly eliminated from plasma by means of a rapid and extensive biotransformation to 13-OH-idarubicin. The 13-dihydroderivative was present at higher and more prolonged levels than the parent compound, with an elimination half-life of about 40 hours.

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“…The results of our phase I trial with the i.v. formulation in patients with solid tumors showed that haematologic toxicity is dose-limiting (6). Compared to doxorubicin and daunorubicin, 4-demethoxydaunorubicin displayed a slower recovery of the blood values and also a somewhat more pronounced thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

Phase-I trial of 4-demethoxydaunorubicin in acute leukaemias

Sessa¹,

Tschopp²,

Fopp³

et al. 1985

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Eleven patients with heavily pretreated acute leukaemia were treated with 4-demethoxydaunorubicin. Dosages were escalated from 7 mg/m2/d to 15 mg/m2/d for 3 consecutive days. One patient achieved a partial remission and antitumor activity was seen in most other patients. Stomatitis was dose-limiting at 15 mg/m2. Phase II trials are warranted and we propose a schedule of 12 mg/m2/d for 3 consecutive days.

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Phase I trial of 4-demethoxydaunorubicin with single i.v. doses

Cited by 29 publications

References 3 publications

Phase I study of oral idarubicin given with a weekly schedule

Phase I study of oral idarubicin given with a weekly schedule

Phase I trial of 4-demethoxydaunorubicin (idarubicin) with single oral doses

Phase-I trial of 4-demethoxydaunorubicin in acute leukaemias

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