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Phase I clinical and pharmacokinetic study of orally administered N -palmitoyl-1-β- d-arabinofuranosylcytosine.

Authors :
Ohno, Ryuzo
Kimura, Kiyoji
Ota, Kazuo
Miura, Yasusada
Hoshino, Akira
Hattori, Kenichi
Hirano, Masami
Ito, Munemoto
Maekawa, Tadashi
Nakamura, Toru
Kimura, Ikuo
Ichimaru, Michito
Uzuka, Yoshiro
Oguro, Masao
Miyazaki, Tamotsu
Sakai, Yasunobu
Hirota, Yutaka
Amaki, Ichita
Osamura, Shigeyuki
Masaoka, Toru
Source :
Medical Oncology & Tumor Pharmacotherapy; Jun1987, Vol. 4 Issue 2, p67-73, 7p
Publication Year :
1987

Abstract

A phase I study of N -palmitoyl-1-β- d-arabinofuranosylcytosine (PLAC) was conducted in 88 patients; 36 with solid tumors and 52 with hematological malignancies, using 2 different schedules. Schedule 1 employed a single oral administration and Schedule 2, 5-day consecutive daily oral administration. In Schedule 1, the daily dose was initiated with 1 mg kg which was escalated up to 24 mg kg according to the modified Fibonacci's method. Side effects included nausea, vomiting and skin rashes, but myelosuppression was not seen within this dose range. In Schedule 2, the daily dose was started with 1 mg kg which was escalated up to 24 mg kg. Major side effects were nausea, vomiting and amorexia, and mild myelosuppression was noted at 12 mg kg or more. The dose-limiting toxicity was gastrointestinal toxicity, which appeared at 3.3 mg kg or more and became frequent at 7 mg kg or more. Pharmacokinetic study revealed that the plasma concentrations of PLAC and ara-C, obtained by the oral intake of 3.3 mg kg or more of PLAC, were sufficient for these compounds to exert cytotoxic effects on various human leukemia cells in vitro. Based on these observations and plausible mechanism of action of PLAC, further clinical study should be carried out in a treatment schedule of considerably prolonged administration period with 3.3-6 mg kg day of PLAC. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
07360118
Volume :
4
Issue :
2
Database :
Complementary Index
Journal :
Medical Oncology & Tumor Pharmacotherapy
Publication Type :
Academic Journal
Accession number :
72117794
Full Text :
https://doi.org/10.1007/BF02934942