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

Summary 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...

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Bibliographic Details
Published in:Investigational new drugs 2010-08, Vol.28 (4), p.509-515
Main Authors: Traynor, Anne M., Gordon, Michael S., Alberti, Dona, Mendelson, David S., Munsey, Mark S., Wilding, George, Gammans, Richard E., Read, William L.
Format: Article
Language:English
Subjects:
Adult
Aged
Angina pectoris
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Benzimidazoles - administration & dosage
Benzimidazoles - adverse effects
Binding sites
Bone marrow
Brain cancer
Cancer therapies
Chemotherapy
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug dosages
Drug Resistance, Neoplasm - drug effects
Drug therapy
Female
Humans
Ischemia
Male
Maximum Tolerated Dose
Medicine
Medicine & Public Health
Middle Aged
Neoplasms - drug therapy
Oncology
Patients
Pharmacokinetics
Pharmacology/Toxicology
Phase I Studies
Sarcoma
Toxicity
Transient ischemic attack
Tubulin Modulators - administration & dosage
Tubulin Modulators - adverse effects
Tumors
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Summary:Summary 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.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-009-9264-2