TY - JOUR
T1 - Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors
AU - Satoh, Taroh
AU - Okamoto, Isamu
AU - Miyazaki, Masaki
AU - Morinaga, Ryotaroh
AU - Tsuya, Asuka
AU - Hasegawa, Yoshikazu
AU - Terashima, Masaaki
AU - Ueda, Shinya
AU - Fukuoka, Masahiro
AU - Ariyoshi, Yutaka
AU - Saito, Toshikazu
AU - Masuda, Noriyuki
AU - Watanabe, Hirokazu
AU - Taguchi, Tetsuo
AU - Kakihara, Toru
AU - Aoyama, Yumiko
AU - Hashimoto, Yohko
AU - Nakagawa, Kazuhiko
N1 - Funding Information:
iodination, Drs. suggestions with the manuscript, and typing. The study was supported by the VA and
PY - 2009/6/1
Y1 - 2009/6/1
N2 - Purpose: YM155, a novel molecular targeted agent, suppresses survivin, a member of the inhibitor of apoptosis protein family that is overexpressed in many tumor types. The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors. Experimental Design: Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21-day cycles. Results: Of the 34 patients enrolled, 33 (median age, 59 years) received at least 1 dose of YM155 (range, 1-19 cycles). The dose levels studied were 1.8, 3.6, 4.8, 6.0, 8.0, and 10.6 mg/m2/d. The MTD was determined to be 8.0 mg/m2/d, based on a dose-limiting toxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m2/d. The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injection-site phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. The pharmacokinetic profile was almost linear over the dosing range and was similar between cycles 1 and 2. Urinary excretion of YM155 showed no definite difference among doses. Stable disease was achieved in nine patients. Conclusions: YM155 was safely administered to patients with advanced refractory solid tumors by 168-hour continuous i.v. infusion in 21-day cycles. The MTD was determined to be 8.0 mg/m2/d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens.
AB - Purpose: YM155, a novel molecular targeted agent, suppresses survivin, a member of the inhibitor of apoptosis protein family that is overexpressed in many tumor types. The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors. Experimental Design: Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21-day cycles. Results: Of the 34 patients enrolled, 33 (median age, 59 years) received at least 1 dose of YM155 (range, 1-19 cycles). The dose levels studied were 1.8, 3.6, 4.8, 6.0, 8.0, and 10.6 mg/m2/d. The MTD was determined to be 8.0 mg/m2/d, based on a dose-limiting toxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m2/d. The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injection-site phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. The pharmacokinetic profile was almost linear over the dosing range and was similar between cycles 1 and 2. Urinary excretion of YM155 showed no definite difference among doses. Stable disease was achieved in nine patients. Conclusions: YM155 was safely administered to patients with advanced refractory solid tumors by 168-hour continuous i.v. infusion in 21-day cycles. The MTD was determined to be 8.0 mg/m2/d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens.
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U2 - 10.1158/1078-0432.CCR-08-1946
DO - 10.1158/1078-0432.CCR-08-1946
M3 - Article
C2 - 19470738
AN - SCOPUS:66649126940
SN - 1078-0432
VL - 15
SP - 3872
EP - 3880
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -
