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Inflammation of Actinic Keratoses During Capecitabine Therapy

Inflammation of Actinic Keratoses During Capecitabine Therapy Capecitabine, an oral prodrug of 5-fluorouracil, is a novel antineoplastic agent used in the treatment of metastatic colon and breast cancers. A seriesof dermatologic reactions associated with oral capecitabine have been reported, including "dermatitis," leopardlike vitiligo, "erythematous rash," onycholysis,palmar-plantar erythrodysesthesia, photoeruption, pyogenic granulomas, radiation recall, and xerosis.1,2 Toour knowledge, we report the first case of inflammation of actinic keratosesas a result of systemic treatment with oral capecitabine. Report of a Case. An 84-year-old woman undergoing chemotherapy for metastatic colorectal carcinoma presented with asymptomatic erythema of the face that began 12 daysafter initiating treatment with capecitabine. A decade prior, she underwent cryotherapy treatment for actinic keratoses on the dorsum of her hands. Shedenied any history of previous skin cancers or sun exposure while undergoing chemotherapy. Photodistributed over the face, arms, and dorsum of the handswere multiple 5- to 15-mm ill-defined pink papules and plaques with adherent white scale (Figure 1). The mucousmembranes were uninvolved. Figure 1. View LargeDownload Photodistributed actinic keratoses on the left side of the face (A) and right hand (B). A biopsy specimen of a representative lesion from the left temple revealed basal keratinocyte atypia with nuclear pleomorphism, overlying parakeratosis,and an associated superficial lichenoid lymphocytic infiltrate (Figure 2). The epidermis was atrophic with scattered dyskeratotic keratinocytes and focal spongiosis. In the superficial dermis, there was prominentsolar elastosis. These findings were interpreted as an actinic keratosis. Figure 2. View LargeDownload Histologic specimen of actinic keratosis from the left temple. A, Basal keratinocyte atypia with overlyingparakeratosis (hematoxylin-eosin, original magnification ×10). B, Higher-power view demonstrating prominent nuclear pleomorphism (hematoxylin-eosin, originalmagnification ×20). Partial resolution of the lesions was noted several days after cessation of capecitabine. No additional treatment was initiated. Comment. Capecitabine is a tumor-selective oral fluoropyrimidine that is metabolized to fluorouracil via a 3-step enzymatic cascade in target tissues. The selectiveuptake of capecitabine at the tumor site results in a sustained exposure of tumor cells to fluorouracil, the active metabolite, while minimizing the exposureof normal tissue.3 Fluorouracil exerts a cytotoxic effect through inhibition of thymidylate synthase, incorporationinto DNA causing strand breaks, and inhibition of RNA synthesis and function.3 Inflammation of actinic keratoses following administration of several systemic chemotherapeutic agents has been documented. Falkson and Schulz4 described the first reported case of inflammationof actinic keratoses with systemic fluorouracil in 1962. Subsequently, cisplatin, deoxycoformycin, doxorubicin, fludarabine phosphate, and dactinomycin-dacarbazine-vincristinesulfate in combination have been associated with this reaction within 1 to 2 weeks of treatment initiation.5 The oral fluoropyrimidines offer several potential advantages over intravenous fluorouracil. The oral medications are easier to use, and have a more favorabletoxicity profile than their intravenous counterparts. In addition, they obviate the need for intravenous access and thus streamline the number of requiredoffice visits. As a result, the use of oral capecitabine is likely to increase, as is the incidence of its cutaneous side effects. As previously suggested,dermatologists need to be familiar with the chemotherapeutic agents and their cutaneous side effects, since we are often consulted by our oncology colleagueswhen patients undergoing chemotherapy develop a rash. It is important that we be able to identify the pathologic process and likely inciting agent, advisewhether the implicated drug may be administered again, and discuss with the oncologist whether recurrence should be anticipated with subsequent treatments. The authors have no relevant financial interest in this article. Reprints are available from Dr Pan. References 1. Willey AGlusac EJBolognia JL Photoeruption in a patient treated with capecitabine (Xeloda) for metastatic breast cancer [letter] J Am Acad Dermatol. 2002;47453PubMedGoogle ScholarCrossref 2. Piguet VBorradori L Pyogenic granuloma-like lesions during capecitabine therapy Br J Dermatol. 2002;1471270- 1272PubMedGoogle ScholarCrossref 3. Liu CY Fluorouracil for allergic reactions to capecitabine Ann Pharmacother. 2002;361897- 1899PubMedGoogle ScholarCrossref 4. Falkson GSchulz E Skin changes in patients treated with 5-fluorouracil Br J Dermatol. 1962;74229- 236PubMedGoogle ScholarCrossref 5. Remlinger KA Cutaneous reactions to chemotherapy drugs: the art of consultation Arch Dermatol. 2003;13977- 81PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Inflammation of Actinic Keratoses During Capecitabine Therapy

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Publisher
American Medical Association
Copyright
Copyright © 2004 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.140.3.367
Publisher site
See Article on Publisher Site

Abstract

Capecitabine, an oral prodrug of 5-fluorouracil, is a novel antineoplastic agent used in the treatment of metastatic colon and breast cancers. A seriesof dermatologic reactions associated with oral capecitabine have been reported, including "dermatitis," leopardlike vitiligo, "erythematous rash," onycholysis,palmar-plantar erythrodysesthesia, photoeruption, pyogenic granulomas, radiation recall, and xerosis.1,2 Toour knowledge, we report the first case of inflammation of actinic keratosesas a result of systemic treatment with oral capecitabine. Report of a Case. An 84-year-old woman undergoing chemotherapy for metastatic colorectal carcinoma presented with asymptomatic erythema of the face that began 12 daysafter initiating treatment with capecitabine. A decade prior, she underwent cryotherapy treatment for actinic keratoses on the dorsum of her hands. Shedenied any history of previous skin cancers or sun exposure while undergoing chemotherapy. Photodistributed over the face, arms, and dorsum of the handswere multiple 5- to 15-mm ill-defined pink papules and plaques with adherent white scale (Figure 1). The mucousmembranes were uninvolved. Figure 1. View LargeDownload Photodistributed actinic keratoses on the left side of the face (A) and right hand (B). A biopsy specimen of a representative lesion from the left temple revealed basal keratinocyte atypia with nuclear pleomorphism, overlying parakeratosis,and an associated superficial lichenoid lymphocytic infiltrate (Figure 2). The epidermis was atrophic with scattered dyskeratotic keratinocytes and focal spongiosis. In the superficial dermis, there was prominentsolar elastosis. These findings were interpreted as an actinic keratosis. Figure 2. View LargeDownload Histologic specimen of actinic keratosis from the left temple. A, Basal keratinocyte atypia with overlyingparakeratosis (hematoxylin-eosin, original magnification ×10). B, Higher-power view demonstrating prominent nuclear pleomorphism (hematoxylin-eosin, originalmagnification ×20). Partial resolution of the lesions was noted several days after cessation of capecitabine. No additional treatment was initiated. Comment. Capecitabine is a tumor-selective oral fluoropyrimidine that is metabolized to fluorouracil via a 3-step enzymatic cascade in target tissues. The selectiveuptake of capecitabine at the tumor site results in a sustained exposure of tumor cells to fluorouracil, the active metabolite, while minimizing the exposureof normal tissue.3 Fluorouracil exerts a cytotoxic effect through inhibition of thymidylate synthase, incorporationinto DNA causing strand breaks, and inhibition of RNA synthesis and function.3 Inflammation of actinic keratoses following administration of several systemic chemotherapeutic agents has been documented. Falkson and Schulz4 described the first reported case of inflammationof actinic keratoses with systemic fluorouracil in 1962. Subsequently, cisplatin, deoxycoformycin, doxorubicin, fludarabine phosphate, and dactinomycin-dacarbazine-vincristinesulfate in combination have been associated with this reaction within 1 to 2 weeks of treatment initiation.5 The oral fluoropyrimidines offer several potential advantages over intravenous fluorouracil. The oral medications are easier to use, and have a more favorabletoxicity profile than their intravenous counterparts. In addition, they obviate the need for intravenous access and thus streamline the number of requiredoffice visits. As a result, the use of oral capecitabine is likely to increase, as is the incidence of its cutaneous side effects. As previously suggested,dermatologists need to be familiar with the chemotherapeutic agents and their cutaneous side effects, since we are often consulted by our oncology colleagueswhen patients undergoing chemotherapy develop a rash. It is important that we be able to identify the pathologic process and likely inciting agent, advisewhether the implicated drug may be administered again, and discuss with the oncologist whether recurrence should be anticipated with subsequent treatments. The authors have no relevant financial interest in this article. Reprints are available from Dr Pan. References 1. Willey AGlusac EJBolognia JL Photoeruption in a patient treated with capecitabine (Xeloda) for metastatic breast cancer [letter] J Am Acad Dermatol. 2002;47453PubMedGoogle ScholarCrossref 2. Piguet VBorradori L Pyogenic granuloma-like lesions during capecitabine therapy Br J Dermatol. 2002;1471270- 1272PubMedGoogle ScholarCrossref 3. Liu CY Fluorouracil for allergic reactions to capecitabine Ann Pharmacother. 2002;361897- 1899PubMedGoogle ScholarCrossref 4. Falkson GSchulz E Skin changes in patients treated with 5-fluorouracil Br J Dermatol. 1962;74229- 236PubMedGoogle ScholarCrossref 5. Remlinger KA Cutaneous reactions to chemotherapy drugs: the art of consultation Arch Dermatol. 2003;13977- 81PubMedGoogle ScholarCrossref

Journal

Archives of DermatologyAmerican Medical Association

Published: Mar 1, 2004

Keywords: inflammation,actinic keratosis,capecitabine

References