| Abstract: |
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. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. |
| Keywords: |
adult; controlled study; aged; aged, 80 and over; middle aged; young adult; major clinical study; sorafenib; placebo; treatment duration; antineoplastic agents; benzenesulfonates; pyridines; reproducibility of results; drug administration schedule; risk factors; prediction; renal cell carcinoma; kidney carcinoma; kidney neoplasms; risk; liver metastasis; lung metastasis; carcinoma, renal cell; models, statistical; scoring system; predictive value of tests; multivariate analysis; leukocyte count; adenocarcinoma, clear cell; gender; hand foot syndrome; administration, oral; predictive value; randomized controlled trial (topic); hand-foot skin reaction; hand-foot syndrome
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