Phase I and pharmacokinetic study of amrubicin, a synthetic 9-aminoanthracycline, in patients with refractory or relapsed lung cancer.

Isamu Okamoto, Akinobu Hamada, Yusuke Matsunaga, Ji ichiro Sasaki, Shinji Fujii, Hideshi Uramoto, Haruhiko Yamagata, Ichiro Mori, Hiroto Kishi, Hiroshi Semba, Hideyuki Saito

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30 Citations (Scopus)

Abstract

Amrubicin is a novel synthetic 9-aminoanthracycline derivative and is converted enzymatically to its C-13 hydroxy metabolite, amrubicinol, whose cytotoxic activity is 10-100 times that of amrubicin. We aimed to determine the maximum tolerated dose (MTD) of amrubicin and to characterize the pharmacokinetics of amrubicin and amrubicinol in previously treated patients with refractory or relapsed lung cancer. The 15 patients were treated with amrubicin intravenously at doses of 30, 35, or 40 mg/m(2) on three consecutive days every 3 weeks for a total of 43 courses. Neutropenia was the major toxicity (grade 4, 67%). The MTD was 40 mg/m(2), with the specific dose-limiting toxicities being grade 4 neutropenia persisting for >4 days, febrile neutropenia, or grade 3 arrhythmia in the three patients treated at this dose. A patient with non-small-cell lung cancer showed a partial response, and ten individuals experienced a stable disease. The area under the plasma concentration versus time curve (AUC) for amrubicin and that for amrubicinol increased with amrubicin dose. The amrubicin AUC was significantly correlated with the amrubicinol AUC. The recommended phase II dose of amrubicin for patients with lung cancer refractory to standard chemotherapy is thus 35 mg/m(2) once a day for three consecutive days every 3 weeks.

Original languageEnglish
Pages (from-to)282-288
Number of pages7
JournalCancer chemotherapy and pharmacology
Volume57
Issue number3
DOIs
Publication statusPublished - Feb 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Okamoto, I., Hamada, A., Matsunaga, Y., Sasaki, J. I., Fujii, S., Uramoto, H., Yamagata, H., Mori, I., Kishi, H., Semba, H., & Saito, H. (2006). Phase I and pharmacokinetic study of amrubicin, a synthetic 9-aminoanthracycline, in patients with refractory or relapsed lung cancer. Cancer chemotherapy and pharmacology, 57(3), 282-288. https://doi.org/10.1007/s00280-005-0051-2