Review
Intralesional agents in the management of cutaneous malignancy: A review

https://doi.org/10.1016/j.jaad.2009.12.013Get rights and content

Intralesional agents have a role in the management of cutaneous malignancies. In this article, the efficacy, side effects, strengths, limitations, costs, and practical considerations regarding the use of intralesional agents to treat basal cell carcinoma, squamous cell carcinoma, selected cutaneous lymphomas, and even metastatic melanoma are reviewed. Intralesional administration of 5-fluorouracil, interferon, interleukin-2, bleomycin with electrochemotherapy, and aminolevulinic acid with photodynamic therapy are discussed as treatment modalities in basal cell carcinoma. Interferon (∼1.5 M IU, 3 times weekly × 3 weeks) is perhaps the most widely used regimen for basal cell carcinoma. With regard to squamous cell carcinoma, treatment with 5-fluorouracil, methotrexate, interferon, and bleomycin are reviewed. Methotrexate (∼0.3-2.0 mL of 12.5 or 25 mg/mL, two injections ∼2 weeks apart) was perhaps the most widely used agent. Interferon (3 M IU × 3 times weekly for ∼8.5 weeks) and rituximab (10-30 mg per lesion, 3 times weekly for 1 week, possibly repeated 4 weeks later) are sometimes used in the management of primary cutaneous B-cell lymphomas, whereas in primary cutaneous CD30+ lymphoma intralesional methotrexate (0.4-0.5 mL of 50 mg/mL weekly for 2 weeks) has been used. Finally, the roles of BCG vaccine, cidofovir, rose bengal, and bleomycin with electrochemotherapy for the palliation of metastatic melanoma are reviewed. Intralesional management appears most useful when surgical intervention is not a viable option, for cases in which the cosmetic outcome may be superior, or for situations in which the side effects from systemic chemotherapeutic agents are to be minimized.

Section snippets

Basal cell carcinoma

BCC is the most common cancer of mankind, comprising over 80% of nonmelanoma skin cancer diagnoses.1, 2 Excision or curettage and electrodessication are often used for treatment of BCC, and are cost-effective with low rates of recurrence. Micrographic surgery claims the lowest recurrence rate, but it is labor-intensive, expensive, and sometimes, geographically restricted. Because surgical or destructive techniques estimate 5-year cure rates to be around 90% for primary BCC, this should be the

Squamous cell carcinoma

SCC is the second most common form of skin cancer in mankind. An estimated 250,000 cases occur annually in the United States, mostly on sun-exposed skin.28 Intralesional therapy focuses on invasive SCC, whereas intraepithelial processes, such as actinic keratosis or SCC in situ (Bowen disease), are more aptly treated with topical modalities.

Keratoacanthoma (KA) is an entity difficult to classify. Initially considered benign, but with a malignant appearance, the concept of KA has blurred, and

Primary cutaneous B-cell lymphomas

Intralesional therapy has been considered for 4 subgroups of primary cutaneous B-cell lymphoma (PCBCL): (1) primary cutaneous follicle-center lymphoma (PCFCL); (2) primary cutaneous marginal zone lymphoma (PCMZL); (3) primary cutaneous diffuse large B-cell lymphoma (PCLBCL), leg type; and (4) PCLBCL, other types.

Speaking generally, PCFCL and PCMZL are associated with an excellent prognosis and have been successfully managed using intralesional agents. PCLBCL leg type maintains a less favorable

CD30+ lymphoproliferative disorders

CD30+ cutaneous lymphoma is the second most common form of cutaneous T-cell lymphoma, superseded only by classic mycosis fungoides. Indeed, over the last several decades, dermatology has recognized a spectrum of disease ranging from lymphomatoid papulosis (classically a “benign” CD30+ disorder) to frank primary cutaneous anaplastic large cell lymphoma (PCALCL). Even for PCALCL, the overall prognosis is generally excellent, with 5-year survival exceeding 90%. Although data are limited to case

Metastatic melanoma

Because depth of invasion is the single most important prognostic factor in melanoma, it would be imprudent to advocate intralesional therapy of a primary melanoma under anything other than the most extraordinary of circumstances. Nevertheless, some investigators have explored the idea of using intralesional agents for control and palliation of metastatic melanoma.

Historically, antiblastics and dinitrochlorobenzene have been used for intralesional management based on strong cytolytic properties.

Conclusion

In sum, a variety of intralesional agents exist to treat common skin malignancies, including: BCC, SCC, some forms of PCBCL and CD30+ T-cell lymphoproliferative disorders, and cutaneous and subcutaneous melanoma metastasis. The intralesional therapies most often used can be seen in Table II. Their costs can be compared in Table III.

Admittedly, management of cutaneous malignancy through the administration of intralesional agents has not been as widely integrated into clinical practice as have

References (66)

  • C.M. Parker et al.

    Large keratoacanthomas in difficult locations treated with intralesional 5-fluoruracil

    J Am Acad Dermatol

    (1986)
  • S. Kraus et al.

    Intratumoral chemotherapy with fluorouracil/epinephrine injectable gel: a nonsurgical treatment of cutaneous squamous cell carcinoma

    J Am Acad Dermatol

    (1998)
  • E.A. Olsen

    The pharmacology of methotrexate

    J Am Acad Dermatol

    (1991)
  • N.M. Annest et al.

    Intralesional methotrexate treatment for keratoacanthoma tumors: a retrospective study and review of the literature

    J Am Acad Dermatol

    (2007)
  • L. Wickramasinghe et al.

    Treatment of neoplastic skin lesions with intralesional interferon

    J Am Acad Dermatol

    (1989)
  • J.J. Grob et al.

    Large keratoacanthomas treated with intralesional interferon alfa-2a

    J Am Acad Dermatol

    (1993)
  • C.K. Oh et al.

    Intralesional interferon alfa-2b treatment of keratoacanthomas

    J Am Acad Dermatol

    (2004)
  • C. De la Torre et al.

    Keratoacanthoma centrifugum marginatum: treatment with intralesional bleomycin

    J Am Acad Dermatol

    (1997)
  • R. Fink-Puches et al.

    Treatment of primary cutaneous B-cell lymphoma with rituximab

    J Am Acad Dermatol

    (2005)
  • J.E. Blume et al.

    Treatment of primary cutaneous CD30+ anaplastic large cell lymphoma with intralesional methotrexate

    J Am Acad Dermatol

    (2006)
  • American Cancer Society. Cancer facts and figures. Available from:...
  • A.I. Rubin et al.

    Basal-cell carcinoma

    N Engl J Med

    (2005)
  • D.E. Rowe et al.

    Long-term recurrence rates in previously untreated (primary) cell carcinoma: implications for patient follow-up

    J Dermatol Surg Oncol

    (1989)
  • D.B. Longley et al.

    5-Fluorouracil: mechanisms of action and clinical strategies

    Nat Rev Cancer

    (2003)
  • H. Bargman et al.

    Topical treatment of Bowen's disease with 5-florouracil

    J Cutan Med Surg

    (2003)
  • K. Gross et al.

    5% 5-Fluorouracil cream for the treatment of small superficial basal cell carcinoma: efficacy, tolerability, cosmetic outcome, and patient satisfaction

    Dermatol Surg

    (2007)
  • C.E. Samuel

    Antiviral actions of interferons

    Clin Microbiol Rev

    (2001)
  • S. Buechner et al.

    Intralesional interferon in basal cell carcinoma: how does it work?

    Recent Results Cancer Res

    (2002)
  • F.J. Bath-Hextall et al.

    Interventions for basal cell carcinoma of the skin [review]

    Cochrane Database Syst Rev

    (2007)
  • L. Kowalzick et al.

    Intralesional recombinant interferon beta-1a in the treatment of basal cell carcinoma: results of an open-label multicenter study

    Eur J Dermatol

    (2002)
  • L. Edwards et al.

    The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas

    Arch Dermatol

    (1990)
  • E. Alpsoy et al.

    Comparison of the effects of intralesional interferon alfa-2a, 2b, and the combination of 2a and 2b in the treatment of basal cell carcinoma

    J Dermatol

    (1996)
  • S. Chimenti et al.

    Use of recombinant interferon alfa-2b in the treatment of basal cell carcinoma

    Dermatology

    (1995)

    • Cited by (87)

    • Dissolvable microneedle particles for enhanced topical drug delivery

      2024, Journal of Drug Delivery Science and Technology

    • Chemotherapeutical treatment of basal cell carcinoma with bleomycin via microinfusion of the drug into the skin (MMP®)

      2023, Anais Brasileiros de Dermatologia

    • Successful treatment of squamous cell carcinoma with intralesional methotrexate

      2022, JAAD Case Reports
      Citation Excerpt :

      The treatments combining surgery with radiotherapy or chemotherapy showed efficiency only in early-stage and well-defined cSCC.8 Intralesional 5-fluorouracil, interferon α, and methotrexate have been used sporadically for the treatment of squamous cell carcinoma.9 A 90-year-old man from Morelia, México, with no significant medical history presented in June 2017 with a 2-cm tumor on the right side of the lower vermilion, extending about 5 mm inside of the oral mucosa.

    • Pancytopenia after administration of intralesional methotrexate in a patient in hemodialysis program

      2021, Medicina Clinica

    • Triple therapy with intralesional 5-fluorouracil, chemowraps, and acitretin: A well-tolerated option for treatment of widespread cutaneous squamous cell carcinomas on the legs

      2019, JAAD Case Reports
      Citation Excerpt :

      The first case noted significant improvement only after acitretin was started, suggesting a synergistic benefit of combining acitretin with intralesional 5-FU and chemowraps. Intralesional 5-FU and chemowraps have been used for SCC treatment2,3 and acitretin for prevention.4 A PubMed search from 1970 until April 2019 using various combinations of the terms acitretin or retinoid and fluorouracil or chemotherapy and leg or extremity finds that their combination has never been reported as a therapeutic option for SCCs.

    • Clinical Efficacy of 5-Fluorouracil and Bleomycin in Dermatology

      2024, Journal of Clinical Medicine
    View all citing articles on Scopus

    Funding sources: None.

    Conflicts of interest: None declared.

    Reprints not available from the authors.

    View full text
    Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.