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Hand-Foot Syndrome

Background

Hand-foot syndrome (HFS), or palmar-plantar erythrodysesthesia (PPE), is commonly associated with long-term fluorouracil treatment and is the most frequently reported side effect of oral capecitabine therapy (≥ 50% of patients).^1,2

It is theorized that HFS may be related to the crushing of deep capillaries in the soles of the feet and palms of the hands, leading to a COX inflammatory-type reaction.³
Symptoms may include

• Numbness
• Tingling
• Swelling
• Erythema
• Pain, blistering, or even desquamation (Figure 1)

Skin reactions may not be noted until the second week of therapy. To control or relieve symptoms, dose reduction or temporary drug cessation may be required (Table 1).

Oncology nurses should instruct patients regarding the possibility of HFS and the need for early communication of symptoms. Because capecitabine is an oral therapy administered at home, this communication of symptoms is crucial. Nurses may assess patient compliance with therapy by suggesting that patients bring in their medication bottles to clinic visits for
pill counts.

Treatment of HFS is largely symptomatic. Patients should be instructed to

• Avoid immersion in hot water, which could exacerbate symptoms
• Avoid activities that may increase pressure in affected areas, such as
  high-impact exercise
• Use topical emollients or other preparations containing urea or lanolin^1,2,3 (Table 2)

Figure 1. Toxicity Grading Scale*: HFS/PPE

Images courtesy of Susan Moore.
*Data from NCI CTCAE v3.0 (page 15)⁵

Studies have evaluated the benefits of celecoxib therapy or pyridoxine treatment to reduce the incidence of HFS; no definitive evidence currently exists to validate these treatments as a standard of care. However, a clinical trial is under way. Click here for details.
(see 10-16-06–Clinical Trial for Hand-Foot Syndrome).

Table 1. Capecitabine Dose Modification Table

Toxicity NCI CTCAE v3.0*	During a Course of Therapy	Dose Adjustment for Next Treatment Cycle, % of Starting Dose
Grade 1	Maintain dose level	Maintain dose level
Grade 2
1st appearance	Interrupt until resolved to grade 0-1	100%
2nd appearance	Interrupt until resolved to grade 0-1	75%
3rd appearance	Interrupt until resolved to grade 0-1	50%
4th appearance	Discontinue treatment permanently
Grade 3
1st appearance	Interrupt until resolved to grade 0-1	75%
2nd appearance	Interrupt until resolved to grade 0-1	50%
3rd appearance	Interrupt until resolved to grade 0-1
Grade 4
1st appearance	Discontinue permanently or If physician deems it to be in the patient's best interest to continue, interrupt until resolved to grade 0-1	50%

Data from Xeloda Web page.⁴
*Data from NCI CTCAE v3.0.⁵

Assessment Tools

Polovich et al include a description of HFS under Cutaneous Toxicity in Side Effects of
Cancer Therapy.⁶

Guidelines for coping with HFS skin problems are available here.

Clinical Practice Guidelines

Evidence-based national guidelines do not currently exist.

Table 2. Patient Management of Hand-Foot Syndrome: Capecitabine Related

Grade	Clinical Feature	Functional Status	Suggested Interventions
1	Numbness, paresthesia, dysesthesia, tingling, painless swelling or erythema of the hands and/or feet	Activities of daily living generally unaffected	Call nurse or doctor when symptoms first appear. Do not “wait and see.” Skin care: Reduce friction and pressure: kneeling for long periods of time; leaning on elbows; power walking, jogging, or regular walking for long periods of time; using hand tools; gardening Wear sunscreen; avoid exposure to heat Use mild soap to bathe; pat (don’t rub) skin dry Keep shower and bath water lukewarm to cool; avoid hot tubs and long exposure to hot water Keep skin moist; gently apply moisturizing creams or topical emollients. Apply at night and wear loose-fitting cotton gloves; avoid rubber ones (dishwashing gloves), since they retain heat Put hands and feet in cool water to relieve symptoms Clothes: Wear comfortable, loose-fitting clothes, shoes, and gloves Wear slippers when possible
2	Painful erythema and swelling of the hands and/or feet, skin remains intact	Activities of daily living more difficult
3	Moist desquamation, ulceration, blistering, or severe pain of the hands and/or feet, tissue breakdown	Activities of daily living interrupted: unable to work; difficulty walking and using hands

Data from NCI CTCAE v3.0 (page 18)⁵ and Wilkes and Doyle.⁷

Case Reports

Several case reports have been published recently regarding another complication as a sequela of HFS with capecitabine. Two cases of acquired palmoplantar keratoderma were noted in patients with metastatic breast cancer, thought to be a sequential event of HFS.⁸ Another published report described HFS with scleroderma-like changes, also thought to be linked to the administration of oral capecitabine, with hyperpigmentation of the palms and soles.⁹ These cases should be noted as single reports, and more information is needed before these side effects can be conclusively linked to capecitabine. Nurses should continue to be vigilant and report to the appropriate agency all new effects and toxicities thought to be drug related.

Drs Saif and Elfiky¹⁰ report on differentiating between the presentation of fluoropyrimidine-associated hand-foot syndrome in white and non-white patients. Three cases illustrating the disparities in white and non-white patients are discussed. The authors suggest a modified grading schema for non-white patients. An algorithm outlines pretreatment patient education and monitoring skin changes during therapy. The reference below links to the full text article without charge.

References

1. Viale PH, Fung A, Zitella L. Advanced colorectal cancer: current treatment and nursing management with economic considerations. Clin J Oncol Nurs. 2005;9:541-552.
2. Berg D. Capecitabine: a new adjuvant option for colorectal cancer. Clin J Oncol Nurs.
   2006;10:479-486.
3. Wilkes GM. Therapeutic options in the management of colon cancer: 2005 update. Clin J Oncol Nurs. 2005;9:31-44.
4. Xeloda Web page. Available at: http://www.xeloda.com. Accessed August 26, 2006.
5. National Cancer Institute common terminology criteria for adverse events v3.0. Available here. Accessed October 26, 2006.
6. Polovich M, White JM, Kelleher LO, eds. Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. Pittsburgh, Pa: ONS Publishing Division; 2005:208.
7. Wilkes GM, Doyle D. Palmar-plantar erythrodysesthesia. Clin J Oncol Nurs. 2005;9:103-106.
8. Do JE, Kim YC. Capecitabine-induced diffuse palmoplantar keratoderma: is it a sequential event of hand-foot syndrome? Clin Exp Dermatol. 2007;May 17 [epub ahead of print].
9. Lee SD, Kim HJ, Hwang SJ, et al. Hand-foot syndrome with scleroderma-like change induced by the oral capecitabine: a case report. Korean J Intern Med. 2007;22:109-112.
10. Saif MW, Elfiky AA. Identifying and treating fluoropyrimidine-associated hand-and-foot syndrome in whites and non-white patients. J Supp Oncol. 2007;5:337-343. http://www.supportiveoncology.net/journal/articles/0507337.pdf

Key Definitions

cyclo-oxygenase (COX)— an enzyme that catalyzes the conversion of arachidonic acid to prostaglandins and is inactivated by aspirin and other NSAIDs

desquamation—peeling off in the form of scales; scaling off, particularly of skin

dysesthesia—impairment of sensitivity, especially to touch

emollient—agent that softens or soothes the skin

erythema—abnormal redness of the skin due to capillary congestion (as in inflammation)

erythrodysesthesia—condition caused by continuous infusion therapy or certain oral chemotherapies resulting in a tingling sensation of the palms and soles, progressing to severe pain and tenderness with erythema and edema

paresthesia—skin sensation, such as burning, prickling, itching, or tingling

pyridoxine—vitamin B₆, found especially in cereals

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This page was last modified on 8/31/2007, at 10:43:57 am ET.

Quick Facts

• Hand-foot syndrome (HFS) is the most frequently reported side effect of oral capecitabine therapy
• HFS is most effectively controlled through a combination of dose reduction or temporary drug cessation and supportive care using skin emollients and protective measures
• No randomized clinical data exist to support the use of cyclo-oxygenase 2 (COX-2) inhibitors or vitamin B₆ (pyridoxine) in the management of HFS