Clinical presentation and management of hand-foot skin reaction associated with sorafenib in combination with cytotoxic chemotherapy: experience in breast cancer

Abstract

Current combination therapies for advanced breast cancer provide a modest survival benefit but with greater toxicity than with monotherapies. New combinations are needed that improve the efficacy of current treatments and have acceptable tolerability profiles. Recent clinical trials have assessed the efficacy and safety of the multikinase inhibitor sorafenib in combination with common treatments for advanced breast cancer. Sorafenib has both antiangiogenic and antiproliferative activities and is indicated for patients with unresectable hepatocellular and advanced renal cell carcinoma. Generally, sorafenib is associated with manageable, non-life-threatening adverse events. One of the more common adverse events seen with sorafenib is hand-foot skin reaction, a dermatologic toxicity usually localized to the pressure points of the palms and soles. Although hand-foot skin reaction is reversible and not life threatening, it can have a significant impact on a patient's quality of life and may necessitate dose modification. Moreover, sorafenib is being evaluated in combination with breast cancer treatments that are associated with a similar dermatologic toxicity (e.g., capecitabine-induced hand-foot syndrome). This review looks at the use of sorafenib in combination with selected chemotherapies in patients with advanced breast cancer and considers the incidence, prevention, and management of hand-foot skin reaction.

Figure 1.

Differentiation of HFSR and HFS [26, 27, 33, 53, 58, 59, 69]. Abbreviations: HFS, hand–foot syndrome; HFSR, hand–foot skin reaction; IP, interphalangeal. Modified with permission from (i) Childress J, Lokich J. Cutaneous hand and foot toxicity associated with cancer chemotherapy. Am J Clin Oncol 2003;26:435–436, with permission. (ii) Photographs reprinted from Autier J, Escudier B, Wechsler J et al. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol 2008;144:886–892 (multikinase inhibitors). Copyright © 2008 American Medical Association. All rights reserved. (iii) Lassere Y, Hoff P. Management of hand-foot syndrome in patients treated with capecitabine (Xeloda). Eur J Oncol Nurs 2004;8(suppl 1):S31–S40 (anthracyclines/antimetabolites), with permission, and photograph courtesy of Mario Lacouture, M.D. (taxane).

Figure 2.

Time to first onset of HFSR/HFS by the Kaplan–Meier method during the SOLTI-0701 trial [47]. (A): Any grade event. (B): Grade 3 events. ^aSafety population (patients who received any study drug[s]). Abbreviations: CAP, capecitabine; HFS, hand–foot syndrome; HFSR, hand–foot skin reaction; PL, placebo; SOR, sorafenib.

Figure 3.

Time course of hand–foot skin reaction (HFSR) associated with sorafenib. (A): Early HFSR after 1 week of 400 mg sorafenib twice daily. (B): Progression of HFSR despite reduction to 400 mg daily and topical mometasone. (C): Sorafenib dosing interrupted, improvement in HFSR within 4 days. After 1 week of interruption, sorafenib was restarted at 400 mg daily without further complications. Reprinted from Degen A, Alter M, Schenck F et al. The hand-foot-syndrome associated with medical tumor therapy—classification and management. J Dtsch Dermatol Ges 2010;8:652–661, with permission.