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


METHODS
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.
Paul P. Carbone Comprehensive Cancer Center, University of Wisconsin, K6/568 CSC, #5669, 600 Highland Avenue, Madison, WI 53792, USA. amt@medicine.wisc.edu
Anne M
AM
Traynor
Michael S
MS
Gordon
Dona
D
Alberti
David S
DS
Mendelson
Mark S
MS
Munsey
George
G
Wilding
Richard E
RE
Gammans
William L
WL
Read
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D050257:Tubulin Modulators; C506648:denibulin