A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors

作者：Traynor Anne M^*; Gordon Michael S; Alberti Dona; Mendelson David S; Munsey Mark S; Wilding George; Gammans Richard E; Read William L

来源：Investigational New Drugs, 2010, 28(4): 509-515.

DOI：10.1007/s10637-009-9264-2

• Phase I
• Vascular disrupting agent
• Angiogenesis
• Pathologic neovascularization

Purpose: To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), safety, and tolerability of MN-209, a novel vascular disrupting agent, in patients with advanced solid tumors. Study Design: MN-029 was administered weekly for three consecutive weeks out of four; two cycles were planned. Dose escalation proceeded by 100% per toxicity criteria. Intra-patient dose escalation was permitted. Results: Twenty patients received a total of 151 infusions of MN-029. No DLTs or grade 4 toxicities occurred. The most common adverse events were nausea, vomiting, arthralgias, and headache. One patient developed acute substernal chest pain 4 days after his first dose of MN-029 and was removed from the study. An MTD was not determined. The recommended phase II dose was identified as 180 mg/m(2)/week. One patient with advanced pancreatic cancer attained a partial response lasting 10 weeks. Conclusions: MN-029 was well tolerated in this schedule. Further development of this class of agents is warranted, especially in combination with other anti-cancer treatments.

• 出版日期2010-8