TY - JOUR
T1 - Initial clinical trial of oral TAC-101, a novel retinoic acid receptor-alpha selective retinoid, in patients with advanced cancer
AU - Rizvi, Naiyer A.
AU - Marshall, John L.
AU - Ness, Elizabeth
AU - Hawkins, Michael J.
AU - Kessler, Craig
AU - Jacobs, Helena
AU - Brenckman, Wayne D.
AU - Lee, Jin S.
AU - Petros, William
AU - Hong, Waun K.
AU - Kurie, Jonathan M.
PY - 2002/8/15
Y1 - 2002/8/15
N2 - Purpose: The goals of this study were to determine the safety, toxicity, and pharmacokinetics of TAC-101, a novel synthetic retinoic acid receptor-alpha (RAR-α) selective retinoid, in patients with advanced cancer. Patients and Methods: Twenty-nine patients at two centers received oral TAC-101 at doses ranging from 12 to 34 mg/m2/d. Pharmacokinetic sampling was performed on days 1 and 28. Results: The most frequent toxicities were myalgia/arthralgia, fatigue, and triglyceridemia. No dose-limiting toxicities were observed within the first 28 days up to 28 mg/m2. However, seven of 21 patients experienced venous thromboembolic events (VTEs) during TAC-101 treatment. Eight additional patients who received 34 mg/m2 were treated after a hypercoagulable work-up to exclude potential risk factors for VTE, and two of eight patients subsequently experienced VTEs. The maximum tolerated dose was exceeded at 34 mg/m2/d within the first 28 days, with one grade 3 hypertriglyceridemia, two grade 3 myalgia/arthralgia, and one grade 3 fatigue. One patient with advanced non-small-cell lung cancer had a complete response. No other responses were observed. No autoinduction of metabolism was observed with dosing over 28 days. Conclusion: This is the first human clinical study with TAC-101, a RAR-α selective retinoid. Musculoskeletal toxicity and hypertriglyceridemia were observed characteristics of previously studied retinoids. The recommended phase II dose is 24 mg/m2 with this treatment schedule. Alternative treatment schedules and prospective evaluation of thrombotic risk will be investigated in subsequent studies.
AB - Purpose: The goals of this study were to determine the safety, toxicity, and pharmacokinetics of TAC-101, a novel synthetic retinoic acid receptor-alpha (RAR-α) selective retinoid, in patients with advanced cancer. Patients and Methods: Twenty-nine patients at two centers received oral TAC-101 at doses ranging from 12 to 34 mg/m2/d. Pharmacokinetic sampling was performed on days 1 and 28. Results: The most frequent toxicities were myalgia/arthralgia, fatigue, and triglyceridemia. No dose-limiting toxicities were observed within the first 28 days up to 28 mg/m2. However, seven of 21 patients experienced venous thromboembolic events (VTEs) during TAC-101 treatment. Eight additional patients who received 34 mg/m2 were treated after a hypercoagulable work-up to exclude potential risk factors for VTE, and two of eight patients subsequently experienced VTEs. The maximum tolerated dose was exceeded at 34 mg/m2/d within the first 28 days, with one grade 3 hypertriglyceridemia, two grade 3 myalgia/arthralgia, and one grade 3 fatigue. One patient with advanced non-small-cell lung cancer had a complete response. No other responses were observed. No autoinduction of metabolism was observed with dosing over 28 days. Conclusion: This is the first human clinical study with TAC-101, a RAR-α selective retinoid. Musculoskeletal toxicity and hypertriglyceridemia were observed characteristics of previously studied retinoids. The recommended phase II dose is 24 mg/m2 with this treatment schedule. Alternative treatment schedules and prospective evaluation of thrombotic risk will be investigated in subsequent studies.
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U2 - 10.1200/JCO.2002.02.090
DO - 10.1200/JCO.2002.02.090
M3 - Article
C2 - 12177113
AN - SCOPUS:0037102143
SN - 0732-183X
VL - 20
SP - 3522
EP - 3532
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 16
ER -