Analysis of toxicity in a phase II study of sorafenib in soft tissue sarcoma (STS)

10061 Background: Sorafenib (BAY 43–9006) is an oral multi-targeted kinase inhibitor. Sorafenib causes dermatologic toxicity and hypertension, although the mechanisms are poorly understood. We observed significant toxicity requiring dose reductions in our phase II study of sorafenib in STS. Methods: 120 patients (40 M, 80 F; median age, 55 years) were treated between 10/05 and 12/06; accrual continues. All patients initially received sorafenib 400 mg BID. 118/120 registered patients were evaluable for toxicity. Clinical and laboratory variables were analyzed for association with dose reduction, using Kruskal-Wallis rank sum test for continuous variables and Fisher exact test for categorical variables. Variables significant at the p=0.05 level were further analyzed with a multivariate logistic regression model for their effects on dose reduction. Results: 53% of patients (63/118) required dose reductions, 53/63 for grade 2 or greater skin toxicity. Most common grade 3–4 drug-related toxicities included lymphopenia (14%), rash (12%), and hand-foot skin reaction (10%). Sex, height, weight, BSA and serum creatinine (Cr) were significantly associated with dose reduction by univariate analysis. Adjusting for sex and/or low serum Cr, BSA was not significantly associated with dose reduction. Sex and low serum Cr were borderline statistically significant predictors of dose reductions when both variables were included in a multivariate model. Only female sex remained a significant predictor when eliminating one outlier with BSA 2.83 (p=0.04). Conclusions: Female gender appears associated with skin toxicity, requiring dose reductions. Based on this multivariate analysis, a starting dose of 400 mg oral daily in women may limit side effects. Correlation with trough serum sorafenib levels is pending. This study is funded in part by NCI Grant P01-CA47179. No significant financial relationships to disclose.