A phase i study of 4′‐0‐tetrahydropyranyladriamycin: Clinical pharmacology and pharmacokinetics

Kasi S. Sridhar, T. S.Anantha Samy, Ram P. Agarwal, Robert C. Duncan, Pasquale Benedetto, Awtar G. Krishan, Charles L. Vogel, Lynn G. Feun, Niramol M. Savaraj, Stephen P. Richman, C. Gordon Zubrod

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14 Scopus citations


A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 α (± SE) of 2.5 ± 0.85 minutes, Tβ 1/2 of 25.6 ± 6.5 minutes, and T 1/2 γ of 23.6 ± 7.6 hours. The area under the curve was 537 ± 149 ng/ml x hours, volume of distribution (V(d)) 3504 ± 644 l/m2, and total clearance (Cl(T)) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was ≤ 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was ≤ 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.

Original languageEnglish (US)
Pages (from-to)2082-2091
Number of pages10
Issue number10
StatePublished - Nov 15 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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