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Case Report

Capecitabine induced HandeFoot Syndrome: Report of two cases Lt Col Sunil Sanghi a, Brig R.S. Grewal,

VSM

b

, Lt Col Biju Vasudevan a,*, A. Nagure c

a

Classified Specialist (Dermatology & Venereology), CH (SC), Pune 40, India Brig i/c Adm & Cdr Tps, Base Hospital, Delhi Cantt, India c Consultant (Dermatology), Bidar, India b

article info Article history: Received 16 August 2011 Accepted 17 January 2012 Available online 14 August 2012 Keywords:

HFS also referred to as palmoplantar erythrodysesthesia manifests as varying degrees of dysesthesia, painful erythema and edema of palms and soles, which may be followed by desquamation of the involved skin. We report two cases of Capecitabine induced HandeFoot Syndrome managed with reduction of dosage, topical emollients and Injection Vitamin B6.

HandeFoot Syndrome Capecitabine 5-Fluorouracil

Introduction Capecitabine is a fluoropyrimidine, a systemic prodrug of 5Fluorouracil (5-FU), with the advantage of oral administration. Capecitabine is currently indicated for use in adjuvant setting for the treatment of colorectal cancer, first line therapy in metastatic colorectal cancer and as monotherapy or in combination with Docetaxel in metastatic breast cancer.1 The commonest dose-dependent toxicities associated with Capecitabine are hyperbilirubinemia, diarrhea and HandeFoot Syndrome (HFS). Drugs that have been associated with HFS include 5-FU, Capecitabine, cytarabine, doxorubiocin, epirubicin, high dose interleukine2, fluorodeoxiuridine, hydroxyurea, mercaptopurine, cyclophosphamide and Docetaxel.2

Case 1 A 30-year-old female presented with a large lump in her left breast and axillary lymphadenopathy. She underwent lumpectomy in January 2006 and was found to have Grade III carcinoma of the breast with dissemination to lungs. In May 2006 modified radical mastectomy and breast reconstruction was done, following which she developed lymphedema of left hand. She had already received 3 cycles of chemotherapy with Adriamycin and Cyclophosphamide wef February 2006. Since January 2008 she was put on palliative chemotherapy with Capecitabine 500 mg to be taken in cycles of 2 weeks with a gap of 1 week in between cycles. After 3 days of the fourth cycle of Capecitabine, she developed peeling of skin and pain over both palms and soles. Two days later she developed severe pain and fissuring of both palms and soles. On examination, patient had erythema and desquamation of both palms, dorsa of all fingers and both soles consistent with grade 1 HFS (Figs. 1 and 2). She had no dysesthesia. She was diagnosed as a case of HFS and managed with reduction of dosage of Capecitabine along with topical emollients. She had resolution of her symptoms in the next 3 months.

* Corresponding author. E-mail address: [email protected] (B. Vasudevan). 0377-1237/$ e see front matter ª 2012, Armed Forces Medical Services (AFMS). All rights reserved. http://dx.doi.org/10.1016/j.mjafi.2012.01.009

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Case 2 A 66-year-old male patient presented in July 2008 with complaints of recurrent abdominal pain. On evaluation he was found to have soft tissue mass involving ileo-caecal junction, caecum and ascending colon. He underwent right hemicolectomy on 19 July 2008 and histopathology revealed well differentiated Adenocarcinoma of the colon, Stage T2,N0,M0. After convalescence he was started on adjuvant chemotherapy with leucovorin and capecitabine wef 04 September 2008. One month later he developed severe erythema, pain and swelling of both palms and soles. Dermatological examination revealed erythema, keratoderma like features of both palms and soles which was more severe in palms and interfered with hand functions (Fig. 3). He was diagnosed as a case of HFS grade 2 and Capecitabine was withheld. He was managed with topical steroids and Injection Vitamin B6, with complete resolution of lesions within 3 months. His chemotherapy was modified to Injection Oxaliplatin subsequently.

Fig. 2 e Similar lesions on feet in Patient 1.

5-FU has been known to cause HFS since the first description by Lokich and Moore in 1984.3 The continued prolonged exposure to 5-FU, provided by oral administration of Capecitabine, leads to high incidence of HFS. The manifestations of HFS are classified into 3 grades according to their severity by the National Cancer Institute Cancer Therapy Evaluation Program.4 Grade 1 consists of erythema of the lateral aspects of the fingers that progress to the thenar and hypothenar eminences, with swelling, numbness, dysesthesia/paresthesia and tingling, especially over the pads of the distal phalanges. The same manifestations occur on the soles, but less frequently on the dorsal aspects of the hands and feet. Grade 2 is progression of Grade 1 manifestations, where pain and discomfort affects the daily activities of the patient. Grade 3 is superimposition of blistering, moist desquamation and ulceration, coupled with severe pain. The pathophysiology of the HFS is largely unknown. It has been hypothesized that 5-FU metabolites and not 5-FU itself,

could be responsible for this toxicity. A second theory is that Capecitabine may be eliminated by the eccrine glands, the resulting excretion causing HFS, since the hands and feet have an increased number of eccrine glands.5 Histopathological changes include vacuolar degeneration of basal keratinocytes, dermal perivascular lymphocytic infiltration, apoptotic keratinocytes and dermal edema.6 Treatment includes topical emollients, antibiotics to prevent secondary infection, topical steroids, Vit B6, cyclooxygenase COX2 inhibitors and discontinuation of the offending drug in severe cases.7 In case of relapse on withdrawal, the offending drug maybe cautiously re-introduced in a lower dose, which may gradually be stepped up.8 It is important to recognize signs and symptoms of Grade 1 HFS in patients receiving Capecitabine to avoid progression to Grade 2 or to a more debilitating Grade 3 disease. We report two cases of HFS, one classical Grade 1 and other showing severe palmoplantar keratoderma like features which almost took 3 months to improve. It is also proposed that the grades of HFS be modified to include manifestations like palmoplantar keratoderma in Grade 3 once similar such cases are reported globally, and hyperpigmentation9 which can occur as an initial manifestation in Grade 1 to complete the clinical spectrum of the syndrome.

Fig. 1 e Erythema and exfoliation on both hands of Patient 1.

Fig. 3 e Palmar keratoderma like features in Patient 2.

Discussion

m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 6 9 ( 2 0 1 3 ) 6 5 e6 7

Conflicts of interest 5.

All authors have none to declare.

references

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white and non-white patients. J Support Oncol. 2007;5(7):337e343. Mrozek-Orlowski ME, Frye DK, Sanborn HM. Capecitabine: nursing implications of a new oral chemotherapeutic agent. Oncol Nurs Forum. 1999;26:753e762. Narasimhan P, Narasimhan S, Hitti IF, Rachita M. Serious hand-and-foot syndrome in black patients treated with capecitabine: report of 3 cases and review of the literature. Cutis. 2004;73:101e106. 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;8:57e63. Clark AS, Vahdat LT. Chemotherapy-induced palmar-plantar erythrodysesthesia syndrome: etiology and emerging therapies. Support Cancer Ther. 2004;1(4):213e218. Surjushe A, Vasani R, Medhekar S, Thakre M, Saple DG. Handfoot syndrome due to capecitabine. Indian J Dermatol. 2008;53:43e44.

Capecitabine induced Hand-Foot Syndrome: Report of two cases.

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