Timing and severity of skin-related adverse events in a phase II trial of sorafenib (BAY43-9006) in patients with advanced thyroid cancer.

Abstract

e17009 Background: We previously conducted a phase II study of sorafenib (BAY43-9006) in advanced thyroid cancer. Rash and Hand-Foot Skin Reaction (HFSR) were two of the most common adverse events (AEs). Because these skin-related AEs affect quality of life, we further explored their time course and management. Methods: Fifty-five patients were treated on UPCC 03305, a phase II study of sorafenib in patients with advanced thyroid cancer from 2006 to 2011. AEs were recorded using CTCAE v.3.0 and reported here if relation to the drug was deemed “possibly-related” or greater. Cycle length was four weeks. Results: No grade 4 or 5 skin toxicity was observed. Forty-nine patients (89%) experienced rash. Thirty-one patients had a maximum severity of grade 1 (56%), eight had grade 2 (15%), and nine had grade 3 (18%). Fifty patients (91%) had HFSR. Thirteen patients had a maximum severity of grade 1 (24%), 33 had grade 2 (60%), and four had grade 3 (7%). The severity of rash peaked at cycle 1 (19% grade 2,3) and declined by cycle 3 (4% grade 2,3). The severity of HFSR peaked at cycle 2 (39%, grade 2,3) and declined by cycle 6 (10% grade 2,3). The timing and severity of rash and HFSR by cycle are reported in the Table. Following cycle 12 the severity and prevalence of skin AEs reached a steady state. Of the 55 patients, 30 patients (55%) required dose-reduction, and nine of those patients (31%) resumed full dose by the end of study date. Nine patients (16%) were dose-reduced for rash, 17 patients (31%) were dose-reduced for HFSR, and three patients (5%) were dose-reduced for both rash and HFSR. Conclusions: The severity of skin toxicity peaked by cycle 1 for rash and cycle 2 for HFSR. The severity improved dramatically for rash by cycle 3 and for HFSR by cycle 6. Our data support the close supervision of skin-related AEs in the first six cycles of treatment with sorafenib. However, the sustained high prevalence of rash and HFSR requires all patients receive ongoing skin care for the duration of therapy. Clinical trial information: NCT00095693. [Table: see text]