Intralesional methotrexate as treatment for multiple refractory squamous cell carcinomas – Drexel – May 16, 2016

Presented by: Brittany Heffner, M.D . and Mark Abdelmalek, MD

Drexel University College of Medicine

May 16, 2016

Intralesional methotrexate may be a viable option for patients with multiple recalcitrant squamous cell carcinomas who are poor surgical candidates. This has been a treatment option for many decades, but it is overwhelminglygenerally underutilized. There is a paucity of clinical trials regarding intralesional methotrexate for squamous cell carcinoma, with most studies focusing on treatment of keratoacanthomas (KAs).

In a rRetrospective analyseis of several clinical studies found an average cure rate of 92% in 38 treated keratoacanthomas. with a total number of 38 KAs treated, an average cure rate of 92 percent has been reported. Adverse effects were rare, but included pancytopenia in patients with renal insufficiency on hemodialysis.

A baseline CBC and assessment of renal function is recommended before starting treatment, and histologic diagnosis is preferred. Using a 30-gauge needle, 0.3 to 2 mL of methotrexate in a concentration of 12.5 mg/mL or 25 mg/mL is injected until an end point of uniform tumor blanching is achieved. With small non-melanoma skin cancers (NMSCs), methotrexate is injected centrally to the base of the lesion. In larger NMSCs, methotrexate is injected into four quadrants as well as into the center of the tumor. One to three injection sessions are usually required, which can be spaced 12 to 38 days apart. A complete blood cell count should be obtained 1 week after each injection.

Other intralesional agents includeavailable to treat SCCs include 5-fluorouracil (5-FU), interferon, and bleomycin. Use of intralesional 5-FU was first reported in 1962. A recent analysis showed that virtually all published case studies investigating treatment of KAs and SCCs with 5-FU showed complete cure: 66 of 68 KAs (97%) and 24 of 25 SCCs (96%). No systemic side effects or abnormal lab findings were reported in these studies. Some patients reported local effects, such as erythema, edema, crusting, and scarring.

In thirty one cases of SCC and nine cases of SCCIS treated with interferon-α-2 or interferon-α-2b, the cure rate was 90%, while cure rate for SCCIS was shown to be 89%. Systemic side effects associated with intralesional interferon included fever, malaise, myalgias, headaches, cytopenias, hepatotoxicity, and nephrotoxicity. Side effects were dose-dependent and laboratory values normalized 5 weeks after treatment.

In three studies for treatment of KAs and one study for treatment of SCCIS, intralesional bleomycin was administered in a 1:1 ratio with an anesthetic such as bupivacaine and lidocaine. All four studies showed a 100 percent cure rate (8 KAs total; 1 SCCIS). No side effects were reported in these studies; however, several rare adverse effects have been reported including localized erythema, edema, pain, eschar formation, sclerotic narrowing of the fingertips, and onychodystrophy. Raynaud’s phenomenon has been reported, but it is rare and occurs more commonly with intravenous administration.

When surgical treatments are not feasible, intralesional chemotherapy may be a safe, cost-effective, and efficacious treatment option for NMSCs. Few clinical trials have studied this modality, yet the few case studies in the literature support the use of these agents. Future research is required to determine the optimal dosing and frequency of administration for these agents.

Good LM, Miller CJ. Intralesional agents in the management of cutaneous malignancy: a review. J Am Acad Dermatol. 2011 Feb;64(2):413-22.
Saitta, Peter. Bleomycin in dermatology: a review of intralesional applications. Derm Surgery. 2008 Oct; 34(10): 1299-1313
Metterle L, Nelson C, Patel N. Intralesional 5-fluorouracil (FU) as a treatment for nonmelanoma skin cancer. J Am Acad Dermatol. 2016 Mar;74(3):552-7
Annest NM(1), VanBeek MJ, Arpey CJ, Whitaker DC. Intralesional methotrexate treatment for keratoacanthoma tumors: A retrospective study and review of the literature. J Am Acad Dermatol. 2007 Jun;56(6):989-93.

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