Development and validation of a prediction index for hand-foot skin reaction in cancer patients receiving sorafenib

BACKGROUND: This study describes a repeated measures prediction index to identify patients at high risk of ≥ grade 2 hand-foot skin reaction (HFSR) before each week of sorafenib therapy. METHODS: Data from 451 patients who received a sorafenib (400 mg bid) as part of a clinical trial were reviewed (Escudier B, Eisen T, Stadler WM et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007; 356: 125–134). Generalized estimating equations were used to develop the final risk model. A risk-scoring algorithm (range 0–58) was then derived from the final model coefficients. External validation was then carried out on a new sample of 1145 patients who received sorafenib under an expanded access program. RESULTS: Pretreatment white blood cell count, female gender, good performance status, presence of lung and liver metastases and number of affected organs were predictors for ≥ grade 2 HFSR. A nonlinear association between HFSR risk and treatment duration was also identified where risk was maximized at week 5 followed by a gradual decline. Before each week of therapy, patients with risk scores >40 would be considered at high risk for developing ≥ grade 2 HFSR. CONCLUSIONS: The application and planned continued refinement of this prediction tool will be an important source of patient-specific risk information for the development of moderate to severe HFSR.