Ask the Experts - How Can One Manage Hand-Foot Syndrome?
Ask the Experts - How Can One Manage Hand-Foot Syndrome?
How can one manage hand-foot syndrome and other cutaneous toxic effects of capecitabine and 5FU-based therapy, other than dose-delay or dose-reduction?
Hand-foot syndrome (HFS) is characterized by erythema, numbness, tingling, and either dysesthesias or parasthesias on the palms or soles. In advanced cases, the syndrome can be frankly painful, with swelling of the cutaneous tissues, and even desquamation, ulceration, or blistering. HFS is commonly associated with capecitabine therapy. HFS may occur with initial courses of therapy, or may develop slowly over time. In the multicenter phase II study of capecitabine used to treat women with chemotherapy-refractory advanced breast cancer, 56% of patients developed HFS, and 10% had severe HFS characterized by severe pain and/or skin breakdown. An even greater incidence has been observed in phase II studies of capecitabine for use in colon cancer patients. This side effect is not unique to capecitabine and has been reported with continuos infusion 5FU and with other oral 5FU analogues.
Treatment cessation, treatment delay, and dose-reduction are accepted measures for managing HFS arising from capecitabine. In the published phase II studies, capecitabine dosing has been held for grade 2 toxicities until these have resolved to grade 1 or less. Subsequent recurrences of the toxicity are managed with 25% to 50% dose reduction of capecitabine, depending on the severity of the reaction. In these trials, severe refractory or recurrent HFS is a not uncommon reason for patients ending protocol-based therapy.
The usefulness of specific treatments for HFS is not well characterized. Patients are usually treated with topical emollients (such as Aquaphor) for symptom relief. Anecdotal clinical observations have led some investigators to treat patients with vitamin B6 (pyridoxine; 50-150 mg orally each day). However, the actual benefit of such a therapy is not known. In a small randomly assigned phase II study, the addition of leucovorin to capecitabine treatment did not seem to alter the frequency or intensity of HFS.
How can one manage hand-foot syndrome and other cutaneous toxic effects of capecitabine and 5FU-based therapy, other than dose-delay or dose-reduction?
Hand-foot syndrome (HFS) is characterized by erythema, numbness, tingling, and either dysesthesias or parasthesias on the palms or soles. In advanced cases, the syndrome can be frankly painful, with swelling of the cutaneous tissues, and even desquamation, ulceration, or blistering. HFS is commonly associated with capecitabine therapy. HFS may occur with initial courses of therapy, or may develop slowly over time. In the multicenter phase II study of capecitabine used to treat women with chemotherapy-refractory advanced breast cancer, 56% of patients developed HFS, and 10% had severe HFS characterized by severe pain and/or skin breakdown. An even greater incidence has been observed in phase II studies of capecitabine for use in colon cancer patients. This side effect is not unique to capecitabine and has been reported with continuos infusion 5FU and with other oral 5FU analogues.
Treatment cessation, treatment delay, and dose-reduction are accepted measures for managing HFS arising from capecitabine. In the published phase II studies, capecitabine dosing has been held for grade 2 toxicities until these have resolved to grade 1 or less. Subsequent recurrences of the toxicity are managed with 25% to 50% dose reduction of capecitabine, depending on the severity of the reaction. In these trials, severe refractory or recurrent HFS is a not uncommon reason for patients ending protocol-based therapy.
The usefulness of specific treatments for HFS is not well characterized. Patients are usually treated with topical emollients (such as Aquaphor) for symptom relief. Anecdotal clinical observations have led some investigators to treat patients with vitamin B6 (pyridoxine; 50-150 mg orally each day). However, the actual benefit of such a therapy is not known. In a small randomly assigned phase II study, the addition of leucovorin to capecitabine treatment did not seem to alter the frequency or intensity of HFS.
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