An exploratory analysis of exposure-toxicity (E-T) relationships with oblimersen sodium; potential for patient management

Abstract

Background Oblimersen sodium is a phosphorothioate antisense oligonucleotide in development for treatment of various cancers in combination with chemotherapy. Aims (1) to perform an exploratory analysis from pooled clinical data to examine oblimersen E-T relationships, (2) to evaluate effects of age and gender on oblimersen exposure. Methods Data analysis techniques were descriptive, including scatter and box plots for continuous and categorical variables, respectively. Linear and logistic regression methods were used to examine correlation of oblimersen exposure with safety indices. Results Data used in this analysis were from 60 subjects (26–76 years of age) from two Phase I/II studies in advanced malignant melanoma and chronic lymphocytic leukemia. Subjects received oblimersen doses ranging from 170–800 mg/day for 5–7 days. A total of 143 dose events were recorded (a dose event being defined as one cycle of oblimersen therapy), of which 60% was obtained from males and 40% from females. Exploratory trend analyses showed that occurrence/grade of fever and headache appeared correlated with oblimersen exposure; however, no statistical significance was observed (p-value > 0.2). Gender and age did not correlate with oblimersen exposure. Conclusions Results from this preliminary analysis of oblimersen E-T relationships provide a framework for formal examination of these relationships in future clinical trials to potentially define dose-adjustments for toxicity management. Clinical Pharmacology & Therapeutics (2005) 77, P87–P87; doi: 10.1016/j.clpt.2004.12.224