Phase I study of liposomal annamycin

Daniel J. Booser, Roman Perez-Soler, Paul Cossum, Laura Esparza-Guerra, Qing Ping Wu, Yiyu Zou, Waldemar Priebe, Gabriel N. Hortobagyi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Annamycin is a highly lipophilic anthracycline with the ability to bypass the MDR-1 mechanism of cellular drug resistance. In this phase I study, annamycin entrapped in liposomes was administered by a 1- to 2-h intravenous infusion at 3-week intervals. Thirty-six patients with relapsed solid tumors were treated and 109 courses were administered at doses ranging from 3 to 240 mg/m2. The dose-limiting toxicity was thrombocytopenia. Five patients had a probable allergic reaction, requiring discontinuation of treatment in one. Treatment was well tolerated otherwise. No cardiac toxicity was seen on endomyocardial biopsy of four patients studied. There was limited gastrointestinal toxicity and no alopecia. No objective tumor responses were observed. Pharmacokinetic studies at 24, 120 and 240 mg/m2 showed a biexponential plasma concentration-versus-time profile. There was a linear relationship between the dose and the maximal plasma concentration with relatively constant plasma clearance values. The maximum tolerated dose (MTD) for liposomal annamycin defined in this study is 210 mg/m2. Because of a subsequent change in the formulation of the drug, future studies will use 190 mg/m2 as the MTD.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume46
Issue number5
StatePublished - 2000
Externally publishedYes

Fingerprint

Toxicity
Maximum Tolerated Dose
Plasmas
Tumors
Drug Compounding
Pharmacokinetics
Biopsy
Anthracyclines
Alopecia
Drug Resistance
Intravenous Infusions
Liposomes
Thrombocytopenia
Pharmaceutical Preparations
Neoplasms
Hypersensitivity
Therapeutics
annamycin
Cardiotoxicity

Keywords

  • Anthracycline
  • Pharmacokinetics
  • Phase I study

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Booser, D. J., Perez-Soler, R., Cossum, P., Esparza-Guerra, L., Wu, Q. P., Zou, Y., ... Hortobagyi, G. N. (2000). Phase I study of liposomal annamycin. Cancer Chemotherapy and Pharmacology, 46(5), 427-432.

Phase I study of liposomal annamycin. / Booser, Daniel J.; Perez-Soler, Roman; Cossum, Paul; Esparza-Guerra, Laura; Wu, Qing Ping; Zou, Yiyu; Priebe, Waldemar; Hortobagyi, Gabriel N.

In: Cancer Chemotherapy and Pharmacology, Vol. 46, No. 5, 2000, p. 427-432.

Research output: Contribution to journalArticle

Booser, DJ, Perez-Soler, R, Cossum, P, Esparza-Guerra, L, Wu, QP, Zou, Y, Priebe, W & Hortobagyi, GN 2000, 'Phase I study of liposomal annamycin', Cancer Chemotherapy and Pharmacology, vol. 46, no. 5, pp. 427-432.
Booser DJ, Perez-Soler R, Cossum P, Esparza-Guerra L, Wu QP, Zou Y et al. Phase I study of liposomal annamycin. Cancer Chemotherapy and Pharmacology. 2000;46(5):427-432.
Booser, Daniel J. ; Perez-Soler, Roman ; Cossum, Paul ; Esparza-Guerra, Laura ; Wu, Qing Ping ; Zou, Yiyu ; Priebe, Waldemar ; Hortobagyi, Gabriel N. / Phase I study of liposomal annamycin. In: Cancer Chemotherapy and Pharmacology. 2000 ; Vol. 46, No. 5. pp. 427-432.
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