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Capecitabine-Induced Hand-Foot Syndrome Complicated by Pseudomonal Superinfection Resulting in Bacterial Sepsis and Death Case Report and Review of the Literature FREE

Fridolin J. Hoesly, MD; Sarah G. Baker, MD; Nilanthi D. Gunawardane, MD; Jonathan A. Cotliar, MD
[+] Author Affiliations

Author Affiliations: Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.


Arch Dermatol. 2011;147(12):1418-1423. doi:10.1001/archdermatol.2011.320.
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Published online

ABSTRACT

Background Hand-foot syndrome (HFS) is a relatively common dermatologic toxic reaction to certain anticancer therapies. Although not life-threatening, this complication can reduce patient quality of life. Dose modification of the inciting agent serves as the most effective management of HFS, although a variety of anecdotal reports suggest that other agents may also be efficacious. We present the first reported case of fatal HFS (to our knowledge) and provide a comprehensive review of this condition.

Observations A 61-year-old woman with metastatic breast cancer who was undergoing treatment with capecitabine developed erythema, fissuring, and erosions over both hands and feet, consistent with HFS. Pseudomonal superinfection leading to bacterial sepsis and death rapidly ensued.

Conclusions Although HFS is widely regarded as a non –life-threatening toxic reaction to cancer treatment, our case demonstrates that infectious complications of this condition can prove fatal. Prevention, early recognition, and implementation of various management strategies for HFS and its infectious complications are important in optimizing patient quality of life and minimizing unfavorable outcomes.

Figures in this Article

Hand-foot syndrome (HFS), also known as palmoplantar erythrodysesthesia or acral erythema, is a localized skin eruption associated with the initiation of therapy with certain chemotherapeutic agents.1,2 It is considered a subtype of toxic erythema of chemotherapy, a term that encompasses a broad spectrum of anticancer medication –induced cutaneous reactions.3 The clinical presentation of HFS is characterized by a prodrome of dysesthesia followed by the development of painful, symmetrical edema and erythema of the palms, digits, and soles that may evolve into blisters and erosions.4,5 Although HFS has the potential to substantially affect quality of life, it is not recognized as a life-threatening condition6 and rarely leads to hospitalization.7 We report a case of HFS that was complicated by pseudomonal superinfection resulting in bacterial sepsis and death and provide a review of the HFS literature focusing on the management of this condition. To our knowledge, this is the first reported case of fatal HFS.

REPORT OF A CASE

A 61-year-old woman with metastatic breast cancer who had been treated with oral lapatinib (1250 mg/d) and capecitabine (1250 mg/m2 twice daily) over the previous 4 years presented with a 3-week history of painful erosions and ulcerations of her hands and feet along with bilateral lower extremity swelling. She denied any other symptoms, and her medical history was otherwise unremarkable. Her other medications included fulvestrant and pamidronate. During the previous 3 years, she had experienced intermittent flares of grades 1 and 2 HFS due to capecitabine use. Her symptoms were successfully treated with fluocinonide cream, 0.05%, and ammonium lactate cream, 12%, although she had not been treating her skin with topical agents before her appointment. Physical examination revealed erythema and fissuring over both palms and circumferential erosions involving her right thumb and left middle finger (Figure 1A). She had bilateral lower extremity edema as well as erythema and erosions over both soles and the web spaces of her feet (Figure 1B). A diagnosis of grade 3 HFS was made according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0, and capecitabine therapy was discontinued. Treatment with mupirocin ointment, econazole cream, and oral ciprofloxacin was initiated because of a clinical suspicion of cutaneous superinfection and the patient's history of Pseudomonas aeruginosa paronychia of her left great toe 7 months earlier. Wound cultures obtained from both the hands and the feet during the initial evaluation yielded pansensitive P aeruginosa. The patient was contacted to discuss the culture results, and at that time she reported the onset of malaise and scleral icterus. She was instructed to go to the emergency department, and on arrival she was found to be in septic shock, with acute kidney injury and hepatic dysfunction, resulting in coagulopathy. Pseudomonal superinfection of the patient's HFS was considered the most likely source of sepsis, although the results of blood cultures remained negative. Despite broad-spectrum intravenous antibiotic therapy and aggressive resuscitative measures, she died less than 24 hours later.

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Graphic Jump Location

Figure 1. Diffuse erythema and fissuring of the palms with focal erosions on the fingers (A) and the right foot (B).

COMMENT

It is well known that HFS can have a dramatic impact on quality of life and can necessitate dose modification or discontinuation of cancer therapy; however, it is not considered a dangerous condition in and of itself. There have been a few reports of HFS leading to tissue necrosis and requiring amputation,8,9 but we report the first death (to our knowledge) due to complications of HFS. In a study evaluating weekly docetaxel plus capecitabine therapy for advanced non –small cell lung cancer, there was 1 reported death due to sepsis as a result of a subungual abscess that formed after onycholysis; however, HFS was not identified as a contributing factor.10 Our case demonstrates the life-threatening potential of HFS and highlights the importance of its prevention, prompt recognition, and appropriate management.

The NCI grading scale is commonly used to rate HFS (categorized as palmar-plantar erythrodysesthesia syndrome and described as redness, marked discomfort, swelling, and tingling of the palms and/or soles) severity on a scale of 1 to 3 (Table 1).11 Almost 80% of patients with HFS present with NCI grade 1 toxicity.4

Table Graphic Jump LocationTable 1. National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Grading of Hand-Foot Syndromea

The most common causes of HFS include capecitabine, cytosine arabinoside (cytarabine), doxorubicin, 5-fluorouracil, and the taxanes.3,4 Our patient developed HFS as a result of capecitabine therapy, which causes this condition in 28% to 74% of treated patients.12 Capecitabine is a prodrug that is enzymatically converted to 5-fluorouracil within tumor cells. The onset of HFS can range from within 24 hours to 10 months of the initiation of chemotherapy, with shorter time to onset and greater severity being associated with higher peak plasma levels and total cumulative dose.2,4,12 Capecitabine-related HFS usually appears within the first 3 cycles of treatment13 and commonly worsens in subsequent cycles,1 as occurred in this case. Our patient was also taking lapatinib, a dual inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2; however, this drug is most commonly associated with the development of skin eruptions that are localized to the trunk.14 In one review, fewer than 1% of the 926 patients who were receiving lapatinib monotherapy developed HFS.14 Of interest, multikinase inhibitors such as sorafenib and sunitinib also cause a similar cutaneous toxic reaction termed hand-foot-skin reaction. This entity has several distinguishing features (Table 2), including localized hyperkeratosis with surrounding erythema over flexural and pressure-bearing areas (Figure 2A),6,19 as opposed to the confluent erythema and desquamation on acral sites that are seen with HFS (Figure 2B). Specifically, the lesions of hand-foot-skin reaction tend to affect the fingertips, heels, and skin over the metatarsophalangeal, metacarpophalangeal, and interphalangeal joints (Figure 2C).6 Some of the histologic findings of hand-foot-skin reaction also differ from those of HFS (Table 2). Both conditions tend to exhibit hyperkeratosis, parakeratosis, and ectatic dermal blood vessels with perivascular lymphohistiocytic infiltrates.4,15,16 Hand-foot-skin reaction, however, frequently has a well-defined horizontal zone of keratinocyte necrosis and discohesion that is distinct from the basal vacuolization or scattered pyknotic cells that are often seen in HFS.15,17

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Graphic Jump Location

Figure 2. Hand-foot-skin reaction (A and C) and hand-foot syndrome (B). A, Hand-foot-skin reaction characterized by localized hyperkeratosis with surrounding erythema over pressure-bearing areas. B, Hand-foot syndrome distinguished from hand-foot-skin reaction by more diffuse and confluent erythema over the plantar surface of the foot. C, Localized hyperkeratosis with a surrounding halo of erythema overlying the metatarsophalangeal joints, typical of hand-foot-skin reaction.

Table Graphic Jump LocationTable 2. Comparison of Hand-Foot Syndrome and Hand-Foot-Skin Reaction

The pathogenesis of HFS is unknown, although a direct toxic effect of chemotherapeutic agents on the skin is considered the most likely mechanism.4,17 Some authors suggest that these medications cause local damage after accumulating within eccrine sweat ducts, helping to explain the typical anatomical distribution of the disease.5,20 Others believe that there may be overexpression of cyclooxygenase 2 in the skin as a result of chemotherapy, with resultant inflammation.1,5 Mechanical pressure on the hands and feet occurring during day-to-day activities may also play a primary role through capillary damage, increasing toxic injury to the skin.2 Thymidine phosphorylase plays a large role in the activation of capecitabine and is more prevalent on the palms of the hands than on the dorsal surfaces. Therefore, the anatomical location of this enzyme may contribute to higher concentrations of toxic capecitabine metabolites in these areas, resulting in local tissue damage.21

The only proven effective treatment for HFS is dose reduction or discontinuation of therapy with the causative medication, depending on HFS severity, with resolution usually occurring within 2 weeks of discontinuation.4 In patients taking capecitabine, treatment should be interrupted for NCI grade 2 or 3 HFS until the grade has improved to 1 or 0. After the first appearance of grade 3 HFS or after the second appearance of grade 2 HFS, dose reduction should occur on reinitiation of treatment, as described in the capecitabine package insert (http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/020896s016lbl.pdf).

Several interventions, both nonpharmacologic and pharmacologic, have been implemented, with varying success, in the prophylaxis and treatment of HFS. Patients should be counseled on strategies to reduce mechanical trauma to the skin, such as avoidance of tight-fitting garments, using gel inserts and cotton socks for the feet, and avoiding excess heat exposure.6,12,22 Minimizing edema through elevation of the hands and feet may be helpful.23 Regional cooling with ice packs has been reported to be useful in HFS prevention, possibly by reducing toxic metabolite levels in cooled areas through vasoconstrictive effects.24 For patients taking capecitabine, the practitioner should ensure that the dosage is adjusted appropriately if the creatinine clearance is less than 50 mL/min to avoid drug accumulation, which can result in increased risk of HFS.12,25

Reported management strategies for HFS due to capecitabine- and 5-fluorouracil –containing regimens are summarized in Table 3. Routine application of topical emollients such as petrolatum-lanolin –based ointments26 and udder cream can be implemented in both the prevention and the treatment of HFS.7,23 Some authors have found treatment with urea cream to be effective,27 although the percentage of patients with moderate or severe HFS symptoms was not decreased by twice daily urea –lactic acid cream in a randomized, double-blind, placebo-controlled phase 3 trial evaluating 137 patients who were receiving capecitabine.37 Topical anesthetics and cold compresses can be useful for symptomatic control.12,23

Table Graphic Jump LocationTable 3. Reported Interventions for Hand-Foot Syndrome (HFS) Caused by Capecitabine and 5-Fluorouracil Therapy

Treatment with systemic medications, including pyridoxine,2833 celecoxib,34 vitamin E,7 and nicotine patches,35 may be tried alone or in conjunction with topical therapies (Table 3). Notably, a randomized, double-blind phase 3 study of 360 patients who were receiving capecitabine did not show any benefit from the use of pyridoxine (200 mg/d) in the prophylaxis or treatment of HFS.38 Although there is a lack of data to strongly support its use, pyridoxine is appealing given its favorable safety profile and the lack of other proven options. Lin et al34 found that the use of celecoxib in patients who were taking capecitabine for metastatic colorectal cancer was associated with a reduced incidence of HFS as well as an increase in tumor response. Nicotine patches35 may help prevent HFS, perhaps through their vasoconstrictive effects.

Adequate control of our patient's HFS was achieved over the course of more than 2 years with the use of high-potency topical steroids and keratolytic creams until she developed grade 3 HFS, requiring capecitabine dose interruption. It is unclear whether our patient would have been able to prevent the onset and severity of HFS had she been using the topical agents before her presentation at our clinic.

There is a paucity of data describing the incidence and best approach to the management of HFS superinfection. Infections complicating HFS are most commonly caused by Staphylococcus or gram-negative organisms.1 In contrast to our case, however, these infections rarely result in significant clinical deterioration.1 Nonetheless, every effort should be made to prevent infectious complications through proper wound care and minimizing loss of skin integrity using the management strategies described herein. Patients should be educated about the symptoms of HFS so that the syndrome can be recognized and treated in a timely manner. This recognition is especially important for patients who are taking oral medications such as capecitabine in an outpatient setting as opposed to medications administered at infusion centers, where nurses and physicians may be available to examine patients with early HFS. Our patient presented for management of her HFS 3 weeks after it developed. Minimizing time between the onset of HFS and evaluation will help prevent potentially serious complications and preserve quality of life.

Cutaneous superinfection is suggested clinically by the development of yellow crust, frank purulence, characteristic odor, or systemic signs such as fever and an elevated white blood cell count. In such cases, infected-appearing areas should be swabbed, and the swabs should be sent for culture and sensitivity analysis. Our patient decompensated rapidly because of bacterial sepsis, resulting in death, despite the initiation of appropriate antibiotic therapy promptly after infection was suspected. Oral antibiotic therapy should therefore not be delayed pending culture results when superinfection is suspected, and we suggest providing coverage against Staphylococcus aureus and gram-negative organisms, including Pseudomonas species, until culture results are available. If the patient has a history of superinfection, past culture data may indicate the most likely causative pathogens and their sensitivities. The patient should be assessed for methicillin-resistant S aureus risk factors and treated appropriately for this organism if necessary. If there is a suspicion of concomitant dermatophyte infection, the use of topical antifungal agents may also be beneficial. There is no currently accepted, evidence-based role for prophylactic topical or systemic antibiotic therapy for HFS of any severity.

In conclusion, HFS should not be merely considered a threat to patient quality of life or as an obstacle that may interfere with cancer therapy. Infectious complications of this condition, although relatively uncommon, can cause significant patient morbidity, with the potential to be fatal in rare instances. Implementing a variety of HFS management strategies, providing good patient education, and appropriately treating HFS superinfection are all important components in ensuring favorable patient outcomes.

ARTICLE INFORMATION

Correspondence: Jonathan A. Cotliar, MD, Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 N St Clair St, Ste 1600, Chicago, IL 60611 (j-cotliar@northwestern.edu).

Accepted for Publication: August 10, 2011.

Author Contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Hoesly and Cotliar. Acquisition of data: Hoesly, Baker, Gunawardane, and Cotliar. Analysis and interpretation of data: Hoesly and Cotliar. Drafting of the manuscript: Hoesly and Cotliar. Critical revision of the manuscript for important intellectual content: Hoesly, Baker, Gunawardane, and Cotliar. Administrative, technical, or material support: Hoesly, Baker, Gunawardane, and Cotliar. Study supervision: Cotliar.

Financial Disclosure: None reported.

Funding/Support: Dr Cotliar is supported by a Career Development Award from the Dermatology Foundation.

REFERENCES

Janusch M, Fischer M, Marsch WCh, Holzhausen HJ, Kegel T, Helmbold P. The hand-foot syndrome —a frequent secondary manifestation in antineoplastic chemotherapy.  Eur J Dermatol. 2006;16(5):494-499
PubMed
Lipworth AD, Robert C, Zhu AX. Hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia): focus on sorafenib and sunitinib.  Oncology. 2009;77(5):257-271
PubMed   |  Link to Article
Bolognia JL, Cooper DL, Glusac EJ. Toxic erythema of chemotherapy: a useful clinical term.  J Am Acad Dermatol. 2008;59(3):524-529
PubMed   |  Link to Article
Nagore E, Insa A, Sanmart ín O. Antineoplastic therapy-induced palmar plantar erythrodysesthesia ( “hand-foot ”) syndrome: incidence, recognition and management.  Am J Clin Dermatol. 2000;1(4):225-234
PubMed   |  Link to Article
Clark AS, Vahdat LT. Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome: etiology and emerging therapies.  Support Cancer Ther. 2004;1(4):213-218
PubMed   |  Link to Article
Lacouture ME, Wu S, Robert C,  et al.  Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib.  Oncologist. 2008;13(9):1001-1011
PubMed   |  Link to Article
Kara IO, Sahin B, Erkisi M. Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.  Breast. 2006;15(3):414-424
PubMed   |  Link to Article
Guenova E, Weber HO, Voykov B,  et al.  Palmar-plantar erythrodysesthesia secondary to sunitinib treatment resulting in necrotic foot syndrome aggravated by background diabetic vascular disease.  Arch Dermatol. 2008;144(8):1081-1082
PubMed   |  Link to Article
Palaia I, Angioli R, Bellati F, Basile S, Rabitti C, Panici PB. Distal phalange necrosis: a severe manifestation of palmar plantar erythrodysesthesia.  Am J Obstet Gynecol. 2006;195(4):e1-e2
PubMed   |  Link to Article
Han JY, Lee DH, Kim HY,  et al.  A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma.  Cancer. 2003;98(9):1918-1924
PubMed   |  Link to Article
 Common Terminology Criteria for Adverse Events (CTCAE) v4.0. National Cancer Institute Web site. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed April 22, 2011
Gressett SM, Stanford BL, Hardwicke F. Management of hand-foot syndrome induced by capecitabine.  J Oncol Pharm Pract. 2006;12(3):131-141
PubMed   |  Link to Article
Heo YS, Chang HM, Kim TW,  et al.  Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy.  J Clin Pharmacol. 2004;44(10):1166-1172
PubMed   |  Link to Article
Lacouture ME, Laabs SM, Koehler M,  et al.  Analysis of dermatologic events in patients with cancer treated with lapatinib.  Breast Cancer Res Treat. 2009;114(3):485-493
PubMed   |  Link to Article
Lacouture ME, Reilly LM, Gerami P, Guitart J. Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib.  Ann Oncol. 2008;19(11):1955-1961
PubMed   |  Link to Article
Gordon KB, Tajuddin A, Guitart J, Kuzel TM, Eramo LR, VonRoenn J. Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy.  Cancer. 1995;75(8):2169-2173
PubMed   |  Link to Article
Beldner M, Jacobson M, Burges GE, Dewaay D, Maize JC Jr, Chaudhary UB. Localized palmar-plantar epidermal hyperplasia: a previously undefined dermatologic toxicity to sorafenib.  Oncologist. 2007;12(10):1178-1182
PubMed   |  Link to Article
Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib.  J Am Acad Dermatol. 2009;60(2):299-305
PubMed   |  Link to Article
Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor.  Arch Dermatol. 2008;144(7):886-892
PubMed   |  Link to Article
Jacobi U, Waibler E, Schulze P,  et al.  Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome?  Ann Oncol. 2005;16(7):1210-1211
PubMed   |  Link to Article
Milano G, Etienne-Grimaldi MC, Mari M,  et al.  Candidate mechanisms for capecitabine-related hand-foot syndrome.  Br J Clin Pharmacol. 2008;66(1):88-95
PubMed   |  Link to Article
Chu D, Lacouture ME, Fillos T, Wu S. Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis.  Acta Oncol. 2008;47(2):176-186
PubMed   |  Link to Article
Saif MW. Capecitabine and hand-foot syndrome.  Expert Opin Drug Saf. 2011;10(2):159-169
PubMed   |  Link to Article
Mangili G, Petrone M, Gentile C, De Marzi P, Vigan ò R, Rabaiotti E. Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling.  Gynecol Oncol. 2008;108(2):332-335
PubMed   |  Link to Article
Poole C, Gardiner J, Twelves C,  et al.  Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients.  Cancer Chemother Pharmacol. 2002;49(3):225-234
PubMed   |  Link to Article
Chin SF, Tchen N, Oza AM, Moore MJ, Warr D, Siu LL. Use of “Bag Balm ” as topical treatment of palmar-plantar erythrodysesthesia syndrome (PPES) in patients receiving selected chemotherapeutic agents [abstract 1632].  Proc Am Soc Clin Oncol. 2001;20:409a
Pendharkar D, Goyal H. Novel and effective management of capecitabine induced hand foot syndrome.  J Clin Oncol. 2004;22(14S):8105
Yoshimoto N, Yamashita T, Fujita T,  et al.  Impact of prophylactic pyridoxine on occurrence of hand-foot syndrome in patients receiving capecitabine for advanced or metastatic breast cancer.  Breast Cancer. 2010;17(4):298-302
PubMed   |  Link to Article
Beveridge RA, Kales AN, Binder RA, Miller JA, Virts SG. Pyridoxine (B6) and amelioration of hand/foot syndrome [abstract 393].  Proc Am Soc Clin Oncol. 1990;9:102a
Mortimer JE, Anderson I. Weekly fluorouracil and high-dose leucovorin: efficacy and treatment of cutaneous toxicity.  Cancer Chemother Pharmacol. 1990;26(6):449-452
PubMed   |  Link to Article
Fabian CJ, Molina R, Slavik M, Dahlberg S, Giri S, Stephens R. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.  Invest New Drugs. 1990;8(1):57-63
PubMed   |  Link to Article
Mortimer J, Lauman MJ, Tan B, Dempsey CL, Shillington AC, Hutchins KS. Pyridoxine treatment and prevention of hand-and-foot syndrome in patients receiving capecitabine.  J Oncol Pharm Pract. 2003;9(4):161-166
Link to Article
Chalermchai T, Tantiphlachiva K, Suwanrusme H, Voravud N, Sriuranpong V. Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia.  Asia Pac J Clin Oncol. 2010;6(3):155-160
PubMed   |  Link to Article
Lin E, Morris JS, Ayers GD. Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity.  Oncology (Williston Park). 2002;16(12):(suppl 14)  31-37
PubMed
Kingsley EC. 5-Fluorouracil dermatitis prophylaxis with a nicotine patch.  Ann Intern Med. 1994;120(9):813
PubMed
Somerfield M, Padberg J, Pfister D,  et al.  ASCO clinical practice guidelines: process, progress, pitfalls, and prospects.  Classic Papers Curr Comments. 2000;4:881-886
Wolf SL, Qin R, Menon SP,  et al; North Central Cancer Treatment Group Study N05C5.  Placebo-controlled trial to determine the effectiveness of a urea/lactic acid –based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5.  J Clin Oncol. 2010;28(35):5182-5187
PubMed   |  Link to Article
Kang YK, Lee SS, Yoon DH,  et al.  Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study.  J Clin Oncol. 2010;28(24):3824-3829
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Diffuse erythema and fissuring of the palms with focal erosions on the fingers (A) and the right foot (B).

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Hand-foot-skin reaction (A and C) and hand-foot syndrome (B). A, Hand-foot-skin reaction characterized by localized hyperkeratosis with surrounding erythema over pressure-bearing areas. B, Hand-foot syndrome distinguished from hand-foot-skin reaction by more diffuse and confluent erythema over the plantar surface of the foot. C, Localized hyperkeratosis with a surrounding halo of erythema overlying the metatarsophalangeal joints, typical of hand-foot-skin reaction.

Tables

Table Graphic Jump LocationTable 1. National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 Grading of Hand-Foot Syndromea
Table Graphic Jump LocationTable 2. Comparison of Hand-Foot Syndrome and Hand-Foot-Skin Reaction
Table Graphic Jump LocationTable 3. Reported Interventions for Hand-Foot Syndrome (HFS) Caused by Capecitabine and 5-Fluorouracil Therapy

References

Janusch M, Fischer M, Marsch WCh, Holzhausen HJ, Kegel T, Helmbold P. The hand-foot syndrome —a frequent secondary manifestation in antineoplastic chemotherapy.  Eur J Dermatol. 2006;16(5):494-499
PubMed
Lipworth AD, Robert C, Zhu AX. Hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia): focus on sorafenib and sunitinib.  Oncology. 2009;77(5):257-271
PubMed   |  Link to Article
Bolognia JL, Cooper DL, Glusac EJ. Toxic erythema of chemotherapy: a useful clinical term.  J Am Acad Dermatol. 2008;59(3):524-529
PubMed   |  Link to Article
Nagore E, Insa A, Sanmart ín O. Antineoplastic therapy-induced palmar plantar erythrodysesthesia ( “hand-foot ”) syndrome: incidence, recognition and management.  Am J Clin Dermatol. 2000;1(4):225-234
PubMed   |  Link to Article
Clark AS, Vahdat LT. Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome: etiology and emerging therapies.  Support Cancer Ther. 2004;1(4):213-218
PubMed   |  Link to Article
Lacouture ME, Wu S, Robert C,  et al.  Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib.  Oncologist. 2008;13(9):1001-1011
PubMed   |  Link to Article
Kara IO, Sahin B, Erkisi M. Palmar-plantar erythrodysesthesia due to docetaxel-capecitabine therapy is treated with vitamin E without dose reduction.  Breast. 2006;15(3):414-424
PubMed   |  Link to Article
Guenova E, Weber HO, Voykov B,  et al.  Palmar-plantar erythrodysesthesia secondary to sunitinib treatment resulting in necrotic foot syndrome aggravated by background diabetic vascular disease.  Arch Dermatol. 2008;144(8):1081-1082
PubMed   |  Link to Article
Palaia I, Angioli R, Bellati F, Basile S, Rabitti C, Panici PB. Distal phalange necrosis: a severe manifestation of palmar plantar erythrodysesthesia.  Am J Obstet Gynecol. 2006;195(4):e1-e2
PubMed   |  Link to Article
Han JY, Lee DH, Kim HY,  et al.  A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma.  Cancer. 2003;98(9):1918-1924
PubMed   |  Link to Article
 Common Terminology Criteria for Adverse Events (CTCAE) v4.0. National Cancer Institute Web site. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. Accessed April 22, 2011
Gressett SM, Stanford BL, Hardwicke F. Management of hand-foot syndrome induced by capecitabine.  J Oncol Pharm Pract. 2006;12(3):131-141
PubMed   |  Link to Article
Heo YS, Chang HM, Kim TW,  et al.  Hand-foot syndrome in patients treated with capecitabine-containing combination chemotherapy.  J Clin Pharmacol. 2004;44(10):1166-1172
PubMed   |  Link to Article
Lacouture ME, Laabs SM, Koehler M,  et al.  Analysis of dermatologic events in patients with cancer treated with lapatinib.  Breast Cancer Res Treat. 2009;114(3):485-493
PubMed   |  Link to Article
Lacouture ME, Reilly LM, Gerami P, Guitart J. Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib.  Ann Oncol. 2008;19(11):1955-1961
PubMed   |  Link to Article
Gordon KB, Tajuddin A, Guitart J, Kuzel TM, Eramo LR, VonRoenn J. Hand-foot syndrome associated with liposome-encapsulated doxorubicin therapy.  Cancer. 1995;75(8):2169-2173
PubMed   |  Link to Article
Beldner M, Jacobson M, Burges GE, Dewaay D, Maize JC Jr, Chaudhary UB. Localized palmar-plantar epidermal hyperplasia: a previously undefined dermatologic toxicity to sorafenib.  Oncologist. 2007;12(10):1178-1182
PubMed   |  Link to Article
Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib.  J Am Acad Dermatol. 2009;60(2):299-305
PubMed   |  Link to Article
Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor.  Arch Dermatol. 2008;144(7):886-892
PubMed   |  Link to Article
Jacobi U, Waibler E, Schulze P,  et al.  Release of doxorubicin in sweat: first step to induce the palmar-plantar erythrodysesthesia syndrome?  Ann Oncol. 2005;16(7):1210-1211
PubMed   |  Link to Article
Milano G, Etienne-Grimaldi MC, Mari M,  et al.  Candidate mechanisms for capecitabine-related hand-foot syndrome.  Br J Clin Pharmacol. 2008;66(1):88-95
PubMed   |  Link to Article
Chu D, Lacouture ME, Fillos T, Wu S. Risk of hand-foot skin reaction with sorafenib: a systematic review and meta-analysis.  Acta Oncol. 2008;47(2):176-186
PubMed   |  Link to Article
Saif MW. Capecitabine and hand-foot syndrome.  Expert Opin Drug Saf. 2011;10(2):159-169
PubMed   |  Link to Article
Mangili G, Petrone M, Gentile C, De Marzi P, Vigan ò R, Rabaiotti E. Prevention strategies in palmar-plantar erythrodysesthesia onset: the role of regional cooling.  Gynecol Oncol. 2008;108(2):332-335
PubMed   |  Link to Article
Poole C, Gardiner J, Twelves C,  et al.  Effect of renal impairment on the pharmacokinetics and tolerability of capecitabine (Xeloda) in cancer patients.  Cancer Chemother Pharmacol. 2002;49(3):225-234
PubMed   |  Link to Article
Chin SF, Tchen N, Oza AM, Moore MJ, Warr D, Siu LL. Use of “Bag Balm ” as topical treatment of palmar-plantar erythrodysesthesia syndrome (PPES) in patients receiving selected chemotherapeutic agents [abstract 1632].  Proc Am Soc Clin Oncol. 2001;20:409a
Pendharkar D, Goyal H. Novel and effective management of capecitabine induced hand foot syndrome.  J Clin Oncol. 2004;22(14S):8105
Yoshimoto N, Yamashita T, Fujita T,  et al.  Impact of prophylactic pyridoxine on occurrence of hand-foot syndrome in patients receiving capecitabine for advanced or metastatic breast cancer.  Breast Cancer. 2010;17(4):298-302
PubMed   |  Link to Article
Beveridge RA, Kales AN, Binder RA, Miller JA, Virts SG. Pyridoxine (B6) and amelioration of hand/foot syndrome [abstract 393].  Proc Am Soc Clin Oncol. 1990;9:102a
Mortimer JE, Anderson I. Weekly fluorouracil and high-dose leucovorin: efficacy and treatment of cutaneous toxicity.  Cancer Chemother Pharmacol. 1990;26(6):449-452
PubMed   |  Link to Article
Fabian CJ, Molina R, Slavik M, Dahlberg S, Giri S, Stephens R. Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.  Invest New Drugs. 1990;8(1):57-63
PubMed   |  Link to Article
Mortimer J, Lauman MJ, Tan B, Dempsey CL, Shillington AC, Hutchins KS. Pyridoxine treatment and prevention of hand-and-foot syndrome in patients receiving capecitabine.  J Oncol Pharm Pract. 2003;9(4):161-166
Link to Article
Chalermchai T, Tantiphlachiva K, Suwanrusme H, Voravud N, Sriuranpong V. Randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia.  Asia Pac J Clin Oncol. 2010;6(3):155-160
PubMed   |  Link to Article
Lin E, Morris JS, Ayers GD. Effect of celecoxib on capecitabine-induced hand-foot syndrome and antitumor activity.  Oncology (Williston Park). 2002;16(12):(suppl 14)  31-37
PubMed
Kingsley EC. 5-Fluorouracil dermatitis prophylaxis with a nicotine patch.  Ann Intern Med. 1994;120(9):813
PubMed
Somerfield M, Padberg J, Pfister D,  et al.  ASCO clinical practice guidelines: process, progress, pitfalls, and prospects.  Classic Papers Curr Comments. 2000;4:881-886
Wolf SL, Qin R, Menon SP,  et al; North Central Cancer Treatment Group Study N05C5.  Placebo-controlled trial to determine the effectiveness of a urea/lactic acid –based topical keratolytic agent for prevention of capecitabine-induced hand-foot syndrome: North Central Cancer Treatment Group Study N05C5.  J Clin Oncol. 2010;28(35):5182-5187
PubMed   |  Link to Article
Kang YK, Lee SS, Yoon DH,  et al.  Pyridoxine is not effective to prevent hand-foot syndrome associated with capecitabine therapy: results of a randomized, double-blind, placebo-controlled study.  J Clin Oncol. 2010;28(24):3824-3829
PubMed   |  Link to Article

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