Minimize Chemotherapy-Induced Hand-Foot Syndrome
Allison Gandey
August 9, 2007 — Palmar-plantar erythrodysesthesia, also called hand-foot syndrome or hand-to-foot syndrome, is an uncomfortable and relatively frequent dermatologic toxic reaction to certain chemotherapeutic agents, and it remains poorly understood. Working to elucidate the problem, experts reporting in a review in the July issue of the
Annals of Oncology discuss the challenges of managing this unfortunate adverse event.
"Palmar-plantar erythrodysesthesia typically presents with dysesthesia and tingling in the hands and feet, which usually appear 2 to 12 days after administration of chemotherapy," note the authors led by Domenica Lorusso, MD, from the department of oncology at Catholic University of the Sacred Heart, in Campobasso, Italy. "These symptoms may progress 3 to 4 days later into symmetrical edema and erythema of the palms and soles."
Erythematous plaques with violaceous and edematous patches in the palms, soles, and other high-pressure areas are usually mild and resolve in a week or 2. The problem may, however, evolve into blistering desquamation, crusting, ulceration, and epidermal necrosis if the next chemotherapy cycle is not delayed or the dose reduced. The reviewers point out that palmar-plantar erythrodysesthesia is often uncomfortable and can interfere with the ability to carry out normal activities.
Commenting on the review in an e-letter to the journal (Jaber R et al.
Ann Oncol. 2007; published online April 11, 2007), Raja Jaber, MD, and colleagues from Stony Brook University Hospital, in New York, called the work "outstanding," and they report having read it with great interest. "As summarized by the Lorusso review, the only treatments so far are anecdotal and rely on topical agents with unclear benefits. Typically, the patients end up receiving a lowered dosage or have their treatments delayed." They emphasize that while dose reduction and schedule lengthening may decrease the incidence and ameliorate symptoms of hand-foot syndrome, there are no studies demonstrating that these altered schedules are equally effective in treating patients with metastatic breast cancer.
Dr. Lorusso and colleagues report the incidence of hand-foot syndrome is increased in patients receiving pegylated liposomal doxorubicin compared with conventional doxorubicin. The new drug is a long-circulating formulation in which doxorubicin hydrochloride is encapsulated within pegylated liposomes. It is approved to treat patients with metastatic breast cancer, advanced ovarian cancer, and acquired immunodeficiency syndrome–related Kaposi's sarcoma.
In studies that utilized the currently approved dose of pegylated liposomal doxorubicin of 50 mg/m2 every 4 weeks, the reviewers suggest that about 50% of patients receiving the product developed hand-foot syndrome and roughly 20% experienced grade 3 symptoms.
The researchers note that studies evaluating the development of hand-foot syndrome specifically associated with new-formulation doxorubicin have not fully identified the mechanism; however, data support the roles of drug excretion in sweat and local pressure as contributors.
Debilitating Complication of Cancer Therapy
"Palmar-plantar erythrodysesthesia is a debilitating complication of pegylated liposomal doxorubicin that can lead to delay, reduction, or discontinuation of chemotherapy," Dr. Jaber and colleagues write in their letter. "In addition, it will be an increasing problem due to a high incidence associated with new biologic multikinase inhibitors such as sorafenib and sunitinib."
The authors report on a case of liposomal doxorubicin–related persistent grade 3 hand-foot syndrome, refractory to the reported treatments, that responded dramatically to a short course of systemic treatment with oral prednisone.
"We propose oral prednisone as a safe treatment modality worth trying if palmar-plantar erythrodysesthesia occurs despite preventive dosages of dexamethasone, pyridoxine, and cooling of extremities," suggest the team from Stony Brook University Hospital. "Definite conclusions as to the efficacy of oral prednisone in the treatment of palmar-plantar erythrodysesthesia will require formal controlled clinical trials," they add.
In the meantime, Dr. Lorusso and colleagues emphasize the importance of patient education for early detection of hand-foot syndrome to minimize discomfort and complications. "At each visit, the patient should be carefully asked about signs and symptoms following the last dose," they explain.
Several pharmacologic and nonpharmacologic treatments have been used to prevent hand-foot syndrome. Nonpharmacologic interventions include avoiding undue pressure or rubbing of the skin and avoiding blood vessel dilation induced by hot showers or sun exposure.
In contrast, cooling is said to result in vasoconstriction, lessening circulation of drug to distal extremities. This in turn may lead to less drug extravasation into surrounding tissue, resulting in less toxicity. It is also possible that lower temperatures stabilize the liposomal configuration, thereby reducing the concentration of unencapsulated doxorubicin, the reviewers suggest.
Pharmacologic agents that have been evaluated for hand-foot syndrome include pyridoxine or vitamin B6, dexamethasone, amifostine, and COX-2 inhibitors. Topical agents are typically used to treat cases, and nonpharmacologic treatments that may relieve symptoms include emollients, aloe vera lotion, and moisturizing creams. Dr. Lorusso and colleagues name Bag Balm, a topical petroleum-lanolin-based ointment with the antiseptic ingredient hydroxyquinoline sulfate. They conclude, "Treatment measures must be started as soon as possible when necessary to help prevent progression of palmar-plantar erythrodysesthesia."
Hand-Foot Syndrome
Hand-foot syndrome, which is also referred to as palmar-plantar erythrodysesthesia(PPE), plantar palmar toxicity, palmoplantar keratoderma, and cutaneous toxicity, is a side effect of some chemotherapy drugs. It results when a small amount of drug leaks out of the smallest blood vessels in the palms of the hands and soles of the feet. The amount of drug in the capillaries of the hands and feet increases due to the friction and subsequent heat that is generated in those extremities. As a result, more drug may leak out of capillaries in these areas. Once out of the blood vessels, the chemotherapy drug damages surrounding tissues.
What is hand-foot syndrome?
Hand-foot syndrome (also called Palmar-Plantar Erythrodysesthesia) is a side effect of some chemotherapy drugs that results when a small amount of drug leaks out of the smallest blood vessels in the palms of the hands and soles of the feet. The amount of drug in the capillaries of the hands and feet increases due to the friction and subsequent heat that is generated in those extremities. As a result, more drug may leak out of capillaries in these areas. Once out of the blood vessels, the chemotherapy drug damages surrounding tissues.
Which drugs cause hand-foot syndrome?
The chemotherapy drugs that have been reported to cause hand-foot syndrome in some patients include:
- Xeloda® (capecitabine )
- Cytosar-U® (cytarabine)
- FUDR® (floxuridine)
- 5-FU (fluorouracil)
- Idamycin® (idarubicin)
- Doxil® (liposomal doxorubicin)
- Sutent® (Sunitinib)
- Nexavar® (Sorafenib)
- Continuous infusion of (Adriamycin®) doxorubicin
What are the symptoms of hand-foot syndrome?
Symptoms of hand-foot syndrome include:
- Tingling or burning
- Redness
- Flaking
- Swelling
- Small blisters
- Small sores on the palms of the hands or soles of the feet
- Eventual skin hardening
How can hand-foot syndrome be prevented?
Changes to your normal, daily activities after receiving intravenous (through a vein) chemotherapy or during treatment with oral chemotherapy may reduce your chances of developing hand-foot syndrome.
Reduce exposure of hands and feet to friction and heat by avoiding the following:
- Hot water (washing dishes, long showers, hot baths)
- Impact on your feet (jogging, aerobics, walking, jumping)
- Using tools that require you to squeeze your hand on a hard surface (garden tools, household tools or appliances, kitchen knives, driving, playing musical instruments)
- Rubbing (vigorously applying lotion or massaging)
How is hand-foot syndrome treated?
Hand-foot syndrome is first treated by temporarily halting chemotherapy treatment. Stopping treatment allows the reaction to resolve and the skin to heal. If necessary, a lower dose may be used when chemotherapy is started again, or the intervals between treatments may be lengthened.
Doctors prefer to stop chemotherapy and interrupt hand-foot syndrome early, before the condition has a chance to progress to its more severe and painful stages. At its most severe, hand-foot syndrome may require treatment in the hospital, especially if infection sets in. It is extremely important to inspect your hands and feet after receiving chemotherapy. Tell your doctor immediately if you have signs or symptoms of hand-foot syndrome.
If you are diagnosed with hand-foot syndrome, your doctor will interrupt your chemotherapy treatments (or if you are taking an oral agent, will ask you to stop taking it) until the reaction goes away and any blisters or sores have healed. Your doctor should then discuss with you recommendations for how your treatment plan should proceed. If this is not your first episode of hand-foot syndrome, or if you had a more severe case, possible options for you and your doctor include beginning chemotherapy again with a lower dose or with more time between treatments, or stopping chemotherapy permanently.
How are the symptoms of hand-foot syndrome managed?
If you have developed hand-foot syndrome, you will be advised of methods you can try to feel better while you are waiting for your skin to heal. Some approaches to managing hand-foot syndrome may include:
Corticosteroids - Steroids work by reducing inflammation. Your doctor may recommend a systemic corticosteroid (such as dexamethasone, as a pill or in a solution taken by mouth) to help relieve the symptoms of hand-foot syndrome.
Dimethyl-sulfoxide (DMSO) - Topical treatment with DMSO has shown activity in treating leakage of chemotherapy drugs into tissues.
Vitamin B6 (pyridoxine) - A small clinical trial has shown that treatment with vitamin B6 can reduce the symptoms of hand-foot syndrome. Discuss with your doctor before taking.
Acetaminophen - Over-the-counter pain relievers such as Tylenol (acetaminophen) may relieve discomfort and pain associated with hand-foot syndrome. Ask your doctor if you should take this medication, especially if you have liver or kidney problems.
What else can I do?
For relief of symptoms associated with hand-foot syndrome, try the following:
- Cool the palms or bottoms of your feet with ice packs for 15 to 20 minutes at a time. Gel soles cooled prior to inserting in your shoes can also be comforting.
- Elevate hands and feet.
- Apply antibiotic ointment on open sores.
- Apply moisturizers liberally to hands and feet, but avoid vigorous rubbing to palms and soles. (Lotions such as Lubriderm, Bag Balm, Udder Cream, and lanolin creams are recommended.)
- Avoid constrictive clothing and wear comfortable shoes with cushioned soles. Do not go barefoot.
- Soak the affected skin in Epsom salt and lukewarm water three to four times a day, if possible.
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