Clearance of basal cell and superficial squamous cell carcinomas after imiquimod therapy

Journal of Drugs in Dermatology, May, 2008 by Emily Warshauer, Bruce L. Warshauer

Abstract

The short-term and long-term outcomes of 108 patients with 122 nodular basal cell carcinomas (BCCs), morpheaform BCCs, or low-risk squamous cell carcinomas (SCCs) treated with imiquimod 5% cream at a community-based dermatology practice were retrospectively reviewed. The overall initial tumor clinical cure rate was 93.4% (114/122), with an initial clinical cure rate of 90% (72/80) for BCCs combined, and 100% (42/42) for SCCs combined. During a median follow-up time of 18 months, there was only 1 recurrence in the 114 tumors considered initially clinically cured. Imiquimod may be an appropriate initial treatment for these tumors in patients with good posttreatment follow-up.

Introduction

Imiquimod is a synthetic toll-like receptor 7 agonist with a low molecular weight(1) The activation of innate immune cells by imiquimod results in the induction of an array of cytokines including interferon-alpha (IFN-a), interleukins (ILs) 1,6, 8, and 12, and tumor necrosis factor-alpha (TNF-a).(2), (3) Originally approved in the US in 1997 as a topical treatment for external anogenital warts, further clinical studies led to the addition in 2004 of superficial basal cell carcinoma (BCC) and actinic keratosis (AK) as indications for im iquimod 5% cream.4'6 After the topical administration of imiquimod, increases in activated dendritic cells and t cells are observed in lesions, as well as an increased expression of genes associated with the activation of macrophages, dendritic cells, cytotoxic t cells, and natural killer cells and genes associated with apoptotic pathways.7'10 Thus, in addition to its actions on innate immune cells, imiquimod's effects on cell-mediated immunity appear to play a role in the clearance of lesions.

In studies of superficial BCCs where the tumor site was excised after treatment to confirm tumor status, histologic clearance rates ranged from 79% to 82% with imiquimod dosed 5 or 7 times per week for 6 weeks.''-'1 A 71% histologic clearance rate has been reported in a study of nodular BCCs with imiquimod dosed 5 times per week.12 There also have been reports of clinical success in treating cases of squamous cell carcinoma (SCC) in situ, as well as invasive SCCs.13'17 Because the excision of the tumor site to confirm clearance limits the ability to determine subsequent recurrences and there is limited information on the treatment of SCCs and morpheaform BCCs, the clinical experience at a dermatology practice was reviewed to characterize the clinical outcomes and long-term recurrence rates in patients with nodular and morpheaform BCCs or SCCs treated with imiquimod 5% cream.

Methods

Patients with a histologic diagnosis of nodular and mo pheaform BCC, SCC in situ, or invasive SCC who received treatment with imiquimod for their case tumor(s) from June 1997 to February 2007 were identified by a manual review of clinical records. Demographic data, biopsy results, treatment regimen, and tumor outcomes wete absttactcd from the identified patients (patient identifiers were removed). For each patient, clinical tumor assessments, inflammation assessments (10-point scale; 0=no inflammation and lO-severe redness with inflammation and crusting), and adverse events reported by the patients also were extracted from each clinic visit record. The data was entered into a spreadsheet (Excel 200411', Microsoft Corp, Redmond, WA) in order to tabulate descriptive statistics. The duration of treatment was calculated from the time the patient was initially prescribed topical medicine treatment to the time the tumor was determined to be clinically cured or the treatment was stopped because the patient was deemed a treatment failure by the treating physician. The follow-up period was calculated from the date that the tumor was determined to be cured to the last observation available for that subject ptior to the last date that an observation was eligible for inclusion (December 4, 2007).

Results

Patients and Tumors

A total of 108 patients (50 males and 58 females) were identified by the primary screening criteria; all of these patients were included in the analyses. The median age of the patients was 65 years (range: 33-97 years). Of these 108 patients, 14 patients had 2 tumors treated, for a total of 122 tumors. There were 69 nodular BCC tumors, 36 SCC tumors, 6 basosquamous tumors, and 11 morpheaform tumors. Of the 11 morpheaform tumors, 2 had been previously treated with Mohs surgery and 1 had prior treatment with electrosurgery. The median diameter of all BCC tumors was 1 cm (range: 0.35-4 cm). The median diameter for the morpheaform BCC tumors only was 1.2 cm (range: 0.7-2.5 cm) with tumor invasion depths ranging from 6 to > 12 mm as determined by the initial biopsies. The median diameter of SCC in situ and invasive SCC tumors was 0.95 cm (range: 0.4-3 cm). The median diametet of the basosquamous tumors was 1.45 cm (range: 0.5-4.5 em). A total of 82 tumors (59 BCCs, 4 basosquamous, 19 SCCs) were located on the face, scalp, or ears. Fifteen tumors (12 BCCs and 3 SCCs) were located on the trunk, excluding the neck. Seven tumors (2 BCCs, 2 ba-sosquamous, 3 SCCs) were on the neck and 18 (8 BCCs and 10 SCCs) were on the extremities. Posttreatment biopsies had been obtained from 13 tumors in 13 patients because of a more severe baseline tumor type (eg, morpheaform BCC) and in the case of 2 additional tumors that had persistent low-grade erythema during treatment.

Treatments Received

Of the 122 tumors treated with imiquimod 5% cream, 13 tumors were started on a cyclic regimen of 2 weeks on and 2 weeks off. In 24 of the tumors treated, the treatment was continuous without any rest periods or cyclic therapy. Of the remaining 85 tumors, a variety of dosing frequencies were applied ranging from 3 times per week increasing up to daily doses. The median treatment length for the 122 tumors was 12 weeks (range: 2-39 weeks) (Table 1)- In 18 tumors (11 BCCs, 1 basosquamous tumor, 7 SCCs), tazarotene 0.1% cream was used in a combination therapy with imiquimod.