Hand-foot syndrome (HFS), also called palmarplantar erythrodysesthesia syndrome (PPES), is a relatively common side effect associated with high dosage chemotherapy treatments involving fluorouracil (5-FU) and drugs belonging to the chemical class called anthracyclines.
Anthracyclines have been widely used since the 1960s as dose-limited chemotherapy drugs for a variety of cancers, particularly leukemia, metastatic breast cancer , ovarian cancer , and colorectal cancer. The most familiar anthracyclines are capecitabine (Xeloda), daunorubicin (Cerubidine), doxorubicin (Adriamycin), idarubicin (Idamycin), and vinorelbine (Navelbine). Each of these drugs is broken down into 5-FU by chemicals inside the cancer cells.
A dose-limited drug is a drug for which the maximum dose is determined by the reactions of an individual patient. Symptoms of HFS usually indicate that a patient is receiving too much 5-FU or a particular anthracycline. In such a case, the dosage of the drug that is causing HFS is usually decreased until these symptoms either disappear completely or become tolerable to the patient.
The primary symptom of HFS is a tingling sensation and/or numbness of the skin, particularly on the palms of the hands or the soles of the feet. Swelling and redness (erythema) often accompany this symptom. In severe cases, the skin may peel, develop ulcerations or blisters, and cause severe pain. In the most extreme cases, symptoms of HFS may make it difficult, or impossible, for the patient to grasp small objects, walk, or conduct other normal daily activities.
The symptoms of HFS are believed to be caused by some of the chemicals that 5-FU is broken down into by the natural biochemical processes of the body. Since all anthracycline drugs chemically breakdown into 5-FU, these drugs will all eventually be broken down into the chemicals that can cause the symptoms of HFS. For reasons that are not clear, some patients seem more prone to developing symptoms of HFS than other patients.
The symptoms of HFS are usually alleviated by lowering the dosage of the drug that the patient is receiving. In severe cases of HFS, it may be necessary to discontinue the use of the drug that is causing these symptoms. In some, but not all, patients the symptoms of HFS are reduced by treatment with steroid-containing skin creams, such as hydrocortisone.
Alternative and complementary therapies
Treatment of the hands and feet with an aloe veracontaining skin cream may help to alleviate some of the symptoms of HFS. Topical treatment of the skin with dimethyl sulfoxide (DMSO) has also been suggested as an alternative treatment.
"Capecitabine gives new life to fluorouracil in treatment of breast cancer." Drugs and Therapy Perspectives 16 (26 September 2000): 1-5.
"Daunorubicin liposomal: First report of palmar-plantar erythrodysesthesia syndrome." Reactions (25 November 2000): 829.
Hui, Yuk Fung and Jorge E. Cortes. "Palmar-Plantar Erythrodysesthesia Syndrome Associated with Liposomal Daunorubicin." Pharmacotherapy 20 (2000): 1221-23.
Markman, M., A. Kennedy, K. Webster, G. Peterson, B. Kulp, and J. Belinson. "Phase 2 trial of liposomal doxorubicin (40 mg/m (2)) in Platinum/Paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum." Gynecologic Oncology 78 (September 2000): 369-72.
Abushullaih, Samer, Everardo Saad, and Paulo M. Hoff. "Characterizing hand-foot syndrome (HFS) caused by capecitabine." ASCO OnLine. 2000. 4 July 2001. <http://www.asco.org/prof/me/html/00abstracts/sm/m_2403.htm>.
"Clinical aspects of Xeloda." Roche Laboratories. 2000. 4 July 2001. <http://www.xeloda.com/clinical/index.html>.
Hoff, P. M., V. Valero, N. Ibrahim, J. Willey, and G. N. Hortobagyi. "Prolonged infusion of vinorelbine causing hand-foot syndrome." ASCO OnLine. 1997. 4 July 2001. <http://www.asco.org/prof/me/html/abstracts/cp/m_840.htm>.
"Prevention and management of Doxil-related side effects: Basic strategies." ASCO OnLine. 1998. 5 July 2001. <http://www.asco.org/prof/me/html/98abstracts/asc/m_281.htm>.
Titgan, M. A. "Prevention of palmar-plantar erythrodysesthesia associated with liposomal-encapsulated doxorubicin by oral dexamethasone." ASCO OnLine. 1997. 5 July 2001. <http://www.asco.org/prof/me/html/abstracts/asc/m_288.htm>.
Vail, D. M., R. Chun, D. H. Thamm, L. D. Garrett, A. J. Cooley, and J. E. Obradovich. "Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with Doxil: A randomized, double-blind clinical trial using a canine model." ASCO OnLine. 1998. 5 July 2001. <http://www.asco.org/prof/me/html/98abstracts/cp/m_878.htm>.
Paul A. Johnson, Ed.M.
—A drug for which the proper dosage is determined by the reaction of each individual patient to the drug.