ABSTRACT
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.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Drug Resistance, Neoplasm/drug effects , Neoplasms/drug therapy , Adult , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Maximum Tolerated Dose , Middle Aged , Tubulin Modulators/administration & dosage , Tubulin Modulators/adverse effectsABSTRACT
BACKGROUND AND PURPOSE: Prehospital stroke scales should identify stroke patients and measure stroke severity. The goal of this study was to identify a subset of the 15 items in the National Institutes of Health Stroke Scale (NIHSS-15) that measures stroke severity and predicts outcomes. METHODS: Using 2 distinct data sets from acute stroke clinical trials, we derived and validated shortened versions of the NIHSS (sNIHSS). Stepwise logistic regression and bootstrap techniques were used in selection of NIHSS-15 items. Areas under the receiver operator characteristic curve (C statistics) were used to compare predictive performance of logistic models incorporating differing versions of the NIHSS. RESULTS: The derivation analyses suggested the 8 NIHSS-15 items that were most predictive of "good outcome" 3 months after stroke, in order of decreasing importance: right leg item, left leg, gaze, visual fields, language, level of consciousness, facial palsy, and dysarthria. The sNIHSS-8 comprises all 8 and the sNIHSS-5, the first 5. In the validation models, C statistics were NIHSS-15=0.80, sNIHSS-8=0.77, and sNIHSS-5=0.76. Statistical comparisons suggested that the NIHSS-15 had better predictive performance than the sNIHSS-8 or the sNIHSS-5; the absolute difference in C statistics was small. There was no significant difference between the sNIHSS-8 and the sNIHSS-5. CONCLUSIONS: Much of the predictive performance of the full NIHSS-15 was retained with a shortened scale, the sNIHSS-5. Shortening the NIHSS-15 will facilitate its use during prehospital evaluations. The sNIHSS severity information may be useful to triage acute stroke patients in communities and to provide a baseline stroke severity for prehospital acute stroke trials.
