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Cancer Chemother Pharmacol. 2011 Nov;68(5):1233-41. doi: 10.1007/s00280-011-1593-0. Epub 2011 Mar 23.

A phase I study of tasisulam sodium (LY573636 sodium), a novel anticancer compound in patients with refractory solid tumors.

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  • 1H. Lee Moffitt Cancer Center, Tampa, FL, USA.



This phase I study was carried out to determine the phase II recommended dose of tasisulam sodium (hereafter, tasisulam), a novel anticancer agent with a unique mechanism of action.


Tasisulam was administered intravenously, every 21 days, in patients with refractory solid tumors using a three-plus-three dose-escalation schema.


Fifty-three patients were enrolled; the first 34 were treated with a flat dose of tasisulam of up to 2,400 mg, the dose level at which all three patients had dose-limiting toxicity (DLT). Controlling for C(max) proved important to reduce the risk of toxicity; therefore, we initially focused on identifying which parameters explained C(max) (end-of-infusion concentration) variability. Pharmacokinetic analysis indicated that C(max) negatively correlates with lean body weight (LBW). Thus, the dosing regimen was revised using a LBW-based algorithm targeting a specific C(max). A loading/chronic dose paradigm was then implemented as pharmacokinetic results revealed a long terminal half-life of tasisulam, likely because of its high-affinity albumin binding. C(max)-based dose escalation was stopped at the 420-μg/mL cohort, in which one of the 16 patients had DLT (transient hepatic transaminase elevation); grade 3/4 hematologic toxicity was noted in later cycles in three patients. Although response was not a primary objective, 33% of heavily pretreated patients with post-dose radiological assessments had stable disease.


Implementation of a novel targeted C(max)-based dosing regimen allowed for the recommendation of a phase II tasisulam dose (loading dose of 420 μg/mL targeted C(max) with all subsequent doses administered at 65% of chronic dose given every 21 days) despite pharmacological challenges posed by high albumin binding.

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