Use of Capecitabine for Actinic Keratoses, Squamous Cell Carcinoma, and Basal Cell Carcinoma | Breast Cancer | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Evaluation of the Use of Capecitabine for the Treatment and Prevention of Actinic Keratoses, Squamous Cell Carcinoma, and Basal Cell CarcinomaA Systematic Review

Educational Objective
To review studies on the use of capecitabine for treating and preventing squamous cell carcinoma.
1 Credit CME
Key Points

Question  What evidence exists for the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions?

Findings  In this systematic review of 16 publications, patients receiving capecitabine chemotherapy for breast and colorectal cancer experienced inflammation of preexisting actinic keratoses. Low-dose capecitabine was associated with a reduced incidence of squamous cell carcinomas in high-risk patients, including solid organ transplant recipients; however, adverse effects may limit its use.

Meaning  The findings suggest that capecitabine chemoprevention may be considered in high-risk patients, such as solid organ transplant recipients, particularly those with a history of multiple squamous cell carcinomas, although additional study is warranted to determine optimal patient selection and dosing as well as long-term safety and efficacy.

Abstract

Importance  Certain patient groups, such as solid organ transplant recipients (SOTRs), have a significantly increased risk of developing skin cancers. The chemotherapeutic drug capecitabine has been used off label as a chemopreventive modality to suppress the development of precancerous skin lesions and squamous cell carcinomas (SCCs).

Objective  To systematically review published studies on the use of capecitabine for the treatment and prevention of precancerous and cancerous skin lesions, with a focus on cutaneous SCC.

Evidence Review  For this systematic review, a literature search was performed using the PubMed and Embase databases in December 2019 for all articles published between January 1, 1998, and December 31, 2019, using the search term capecitabine paired with each of the following terms: actinic keratosis, actinic keratoses, squamous cell carcinoma, and basal cell carcinoma. Articles on the use of capecitabine for the treatment and prevention of actinic keratoses (AKs), SCCs, and basal cell carcinomas (BCCs) were selected for inclusion.

Findings  Sixteen publications met the criteria for inclusion, with 8 case reports describing the inflammation of AKs in patients with solid organ cancer treated with capecitabine (2 patients with breast cancer and 6 patients with colorectal cancer). One case report and 1 case series of 4 patients investigated the use of capecitabine for the treatment of advanced or widespread cutaneous SCCs. A total of 6 publications (3 case reports and 3 case series) described the use of capecitabine to prevent development of SCCs in SOTRs. Of these case series, 2 studies found a significant reduction in SCC incidence rate during treatment with capecitabine compared with before treatment. Adverse effects, such as fatigue, nausea, vomiting, diarrhea, elevated creatinine level, hand-foot syndrome, hyperuricemia, weight loss, anemia, and cardiomyopathy, limited the duration of chemoprevention in several patients.

Conclusions and Relevance  Capecitabine treatment may be associated with a decrease in the incidence of SCCs in SOTRs. Capecitabine treatment may also be associated with a decrease in AK and BCC incidence. However, practitioners must weigh this benefit against the risk of adverse effects for each patient individually. Further investigation with a prospective clinical trial is warranted.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: May 14, 2020.

Corresponding Author: Rajiv I. Nijhawan, MD, Department of Dermatology, University of Texas Southwestern Medical Center, 5939 Harry Hines Blvd, Ste 400, Dallas, TX 75390 (rajiv.nijhawan@utsouthwestern.edu).

Published Online: July 8, 2020. doi:10.1001/jamadermatol.2020.2327

Author Contributions: Drs Nijhawan and Schauder 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.

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Schauder, Kim.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Schauder, Kim.

Administrative, technical, or material support: Nijhawan.

Supervision: Kim, Nijhawan.

Conflict of Interest Disclosures: None reported.

References
1.
Hartevelt  MM , Bavinck  JN , Kootte  AM , Vermeer  BJ , Vandenbroucke  JP .  Incidence of skin cancer after renal transplantation in the Netherlands.   Transplantation. 1990;49(3):506-509. doi:10.1097/00007890-199003000-00006 PubMedGoogle ScholarCrossref
2.
Jensen  P , Hansen  S , Møller  B ,  et al.  Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens.   J Am Acad Dermatol. 1999;40(2, pt 1):177-186. doi:10.1016/S0190-9622(99)70185-4 PubMedGoogle ScholarCrossref
3.
Moloney  FJ , Comber  H , O’Lorcain  P , O’Kelly  P , Conlon  PJ , Murphy  GM .  A population-based study of skin cancer incidence and prevalence in renal transplant recipients.   Br J Dermatol. 2006;154(3):498-504. doi:10.1111/j.1365-2133.2005.07021.x PubMedGoogle ScholarCrossref
4.
Krynitz  B , Edgren  G , Lindelöf  B ,  et al.  Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008—a Swedish population-based study.   Int J Cancer. 2013;132(6):1429-1438. doi:10.1002/ijc.27765 PubMedGoogle ScholarCrossref
5.
O’Neill  JP , Sexton  DJ , O’Leary  E ,  et al; The Irish Transplant Cancer Group.  Post-transplant malignancy in solid organ transplant recipients in Ireland.   Clin Transplant. 2019;33(10):e13669. doi:10.1111/ctr.13669 PubMedGoogle Scholar
6.
Menzies  S , O’Leary  E , Callaghan  G ,  et al.  Declining incidence of keratinocyte carcinoma in organ transplant recipients.   Br J Dermatol. 2019;181(5):983-991. doi:10.1111/bjd.18094 PubMedGoogle ScholarCrossref
7.
Krynitz  B , Olsson  H , Lundh Rozell  B , Lindelöf  B , Edgren  G , Smedby  KE .  Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study.   Br J Dermatol. 2016;174(1):95-103. doi:10.1111/bjd.14153 PubMedGoogle ScholarCrossref
8.
Bouwes Bavinck  JN , Hardie  DR , Green  A ,  et al.  The risk of skin cancer in renal transplant recipients in Queensland, Australia: a follow-up study.   Transplantation. 1996;61(5):715-721. doi:10.1097/00007890-199603150-00008 PubMedGoogle ScholarCrossref
9.
Hollenbeak  CS , Todd  MM , Billingsley  EM , Harper  G , Dyer  A-M , Lengerich  EJ .  Increased incidence of melanoma in renal transplantation recipients.   Cancer. 2005;104(9):1962-1967. doi:10.1002/cncr.21404 PubMedGoogle ScholarCrossref
10.
Le Mire  L , Hollowood  K , Gray  D , Bordea  C , Wojnarowska  F .  Melanomas in renal transplant recipients.   Br J Dermatol. 2006;154(3):472-477. doi:10.1111/j.1365-2133.2005.07094.x PubMedGoogle ScholarCrossref
11.
Robbins  HA , Clarke  CA , Arron  ST ,  et al.  Melanoma risk and survival among organ transplant recipients.   J Invest Dermatol. 2015;135(11):2657-2665. doi:10.1038/jid.2015.312 PubMedGoogle ScholarCrossref
12.
Ascha  M , Ascha  MS , Tanenbaum  J , Bordeaux  JS .  Risk factors for melanoma in renal transplant recipients.   JAMA Dermatol. 2017;153(11):1130-1136. doi:10.1001/jamadermatol.2017.2291 PubMedGoogle ScholarCrossref
13.
Fattouh  K , Ducroux  E , Decullier  E ,  et al.  Increasing incidence of melanoma after solid organ transplantation: a retrospective epidemiological study.   Transpl Int. 2017;30(11):1172-1180. doi:10.1111/tri.13011 PubMedGoogle ScholarCrossref
14.
Stasko  T , Hanlon  AM . Epidemiology and risk factors for skin cancer in solid organ transplant recipients. UpToDate. Accessed April 9, 2020. https://www.uptodate.com/contents/epidemiology-and-risk-factors-for-skin-cancer-in-solid-organ-transplant-recipients
15.
Lott  DG , Manz  R , Koch  C , Lorenz  RR .  Aggressive behavior of nonmelanotic skin cancers in solid organ transplant recipients.   Transplantation. 2010;90(6):683-687. doi:10.1097/TP.0b013e3181ec7228 PubMedGoogle ScholarCrossref
16.
Abdel-Wahab  N , Safa  H , Abudayyeh  A ,  et al.  Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature.   J Immunother Cancer. 2019;7(1):106. doi:10.1186/s40425-019-0585-1 PubMedGoogle ScholarCrossref
17.
Que  SKT , Zwald  FO , Schmults  CD .  Cutaneous squamous cell carcinoma: management of advanced and high-stage tumors.   J Am Acad Dermatol. 2018;78(2):249-261. doi:10.1016/j.jaad.2017.08.058 PubMedGoogle ScholarCrossref
18.
Saif  MW , Katirtzoglou  NA , Syrigos  KN .  Capecitabine: an overview of the side effects and their management.   Anticancer Drugs. 2008;19(5):447-464.PubMedGoogle Scholar
19.
Lewis  KG , Lewis  MD , Robinson-Bostom  L , Pan  TD .  Inflammation of actinic keratoses during capecitabine therapy.   Arch Dermatol. 2004;140(3):367-368. doi:10.1001/archderm.140.3.367PubMedGoogle ScholarCrossref
20.
Higa  GM , Kovach  RF , Abraham  J .  Actinic keratosis and capecitabine therapy.   J Oncol Pharm Pract. 2005;11(4):151-153. doi:10.1191/1078155205jp163cr PubMedGoogle ScholarCrossref
21.
Peramiquel  L , Dalmau  J , Puig  L , Roé  E , Fernández-Figueras  MT , Alomar  A .  Inflammation of actinic keratoses and acral erythrodysesthesia during capecitabine treatment.   J Am Acad Dermatol. 2006;55(5)(suppl):S119-S120. doi:10.1016/j.jaad.2005.11.1100PubMedGoogle ScholarCrossref
22.
Krathen  M , Treat  J , James  WD .  Capecitabine induced inflammation of actinic keratoses.   Dermatol Online J. 2007;13(4):13.PubMedGoogle Scholar
23.
Serrão  VV , Feio  AB .  Inflammation of actinic keratoses with capecitabine therapy for colon cancer.   Eur J Dermatol. 2008;18(2):200.PubMedGoogle Scholar
24.
Al-Niaimi  F , Lyon  C .  Resolving actinic keratoses: an expected side-effect of capecitabine therapy.   Clin Exp Dermatol. 2012;37(1):68-69. doi:10.1111/j.1365-2230.2011.04114.x PubMedGoogle Scholar
25.
Stanciu  M , Aubut  N , Gagné  E , Thibeault  MM .  Capecitabine-induced inflammation of actinic keratosis: case report and literature review.   J Cutan Med Surg. 2012;16(5):298-299. doi:10.1177/120347541201600504 PubMedGoogle Scholar
26.
Pigem  R , Maroñas-Jiménez  L , Pau-Charles  I , Mascaró  JM  Jr .  Multiple inflammatory lesions in an oncology patient.   Int J Dermatol. 2016;55(12):1301-1303. doi:10.1111/ijd.13144 PubMedGoogle Scholar
27.
Endrizzi  BT , Lee  PK .  Management of carcinoma of the skin in solid organ transplant recipients with oral capecitabine.   Dermatol Surg. 2009;35(10):1567-1572. doi:10.1111/j.1524-4725.2009.01277.x PubMedGoogle Scholar
28.
Jirakulaporn  T , Endrizzi  B , Lindgren  B , Mathew  J , Lee  PK , Dudek  AZ .  Capecitabine for skin cancer prevention in solid organ transplant recipients.   Clin Transplant. 2011;25(4):541-548. doi:10.1111/j.1399-0012.2010.01348.x PubMedGoogle Scholar
29.
Endrizzi  B , Ahmed  RL , Ray  T , Dudek  A , Lee  P .  Capecitabine to reduce nonmelanoma skin carcinoma burden in solid organ transplant recipients.   Dermatol Surg. 2013;39(4):634-645. doi:10.1111/dsu.12049 PubMedGoogle Scholar
30.
Wollina  U , Hansel  G , Koch  A , Köstler  E .  Oral capecitabine plus subcutaneous interferon alpha in advanced squamous cell carcinoma of the skin.   J Cancer Res Clin Oncol. 2005;131(5):300-304. doi:10.1007/s00432-004-0656-6 PubMedGoogle Scholar
31.
Desimone  J , Beatson  M .  Innumerable squamous cell carcinomas in Vietnam War veteran exposed to chemical defoliants.   J Clin Aesthet Dermatol. 2019;12(8):47-50.PubMedGoogle Scholar
32.
Konda  S , Patel  VA , O’Bryan  KW , Ratner  D .  Fibrohistiocytic tumors in a lung transplant patient taking oral capecitabine for nonmelanoma skin cancer chemoprevention.   Dermatol Surg. 2014;40(7):807-810.PubMedGoogle Scholar
33.
Parikh  SA , Markovic  SN , Brewer  JD .  Oral capecitabine to prevent recurrent cutaneous squamous cell carcinoma in a lung transplant recipient.   Int J Dermatol. 2015;54(9):e358-e360. doi:10.1111/ijd.12682 PubMedGoogle Scholar
34.
Breithaupt  AD , Beynet  D , Soriano  T .  Capecitabine for squamous cell carcinoma reduction in solid organ transplant recipients.   JAAD Case Rep. 2015;1(6)(suppl 1):S16-S18. doi:10.1016/j.jdcr.2015.09.009 PubMedGoogle Scholar
35.
O’Reilly Zwald  F , Brown  M .  Skin cancer in solid organ transplant recipients: advances in therapy and management, part I: epidemiology of skin cancer in solid organ transplant recipients.   J Am Acad Dermatol. 2011;65(2):253-261. doi:10.1016/j.jaad.2010.11.062 PubMedGoogle Scholar
36.
Sun  JF , Wu  RR , Norris  C ,  et al.  Safety of chronic low-dose capecitabine as maintenance therapy in gastrointestinal cancers.   Gastrointest Cancer Res. 2009;3(4):134-140.PubMedGoogle Scholar
37.
Dooley  M , Goa  KL .  Capecitabine.   Drugs. 1999;58(1):69-76. doi:10.2165/00003495-199958010-00006 PubMedGoogle Scholar
38.
McGavin  JK , Goa  KL .  Capecitabine: a review of its use in the treatment of advanced or metastatic colorectal cancer.   Drugs. 2001;61(15):2309-2326. doi:10.2165/00003495-200161150-00015 PubMedGoogle Scholar
39.
Otley  CC , Stasko  T , Tope  WD , Lebwohl  M .  Chemoprevention of nonmelanoma skin cancer with systemic retinoids: practical dosing and management of adverse effects.   Dermatol Surg. 2006;32(4):562-568. doi:10.1097/00042728-200604000-00015 PubMedGoogle Scholar
40.
Stasko  T , Hanlon  AM . Prevention and management of skin cancer in solid organ transplant recipients. UpToDate. Accessed April 9, 2020. https://www.uptodate.com/contents/prevention-and-management-of-skin-cancer-in-solid-organ-transplant-recipients
41.
Collins  L , Quinn  A , Stasko  T .  Skin cancer and immunosuppression.   Dermatol Clin. 2019;37(1):83-94. doi:10.1016/j.det.2018.07.009 PubMedGoogle Scholar
42.
Xeloda (capecitabine). Package insert. Hoffmann-La Roche, Inc: March 2015. Accessed April 19, 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020896s037lbl.pdf
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close