Subject disposition during the study. BCC indicates basal cell carcinoma.
A 75-year-old woman with an infiltrative basal cell carcinoma (BCC) lesion on her right cheek. A, Prior to treatment with imiquimod 3 times per week for 8 weeks. B, At the end of the treatment period, showing marked erosion and crusting. C, After 5 years, showing hypopigmentation and clinical resolution of her BCC lesion.
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Vidal D, Matías-Guiu X, Alomar A. Fifty-five Basal Cell Carcinomas Treated With Topical Imiquimod: Outcome at 5-Year Follow-up. Arch Dermatol. 2007;143(2):264–276. doi:10.1001/archderm.143.2.266
Copyright 2007 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2007
Noninvasive immunobiologic therapy with topical imiquimod, 5%, cream is an emerging therapeutic option for basal cell carcinoma (BCC). Despite the documented short-term efficacy of imiquimod for superficial BCC, few data exist on the long-term course of imiquimod-treated BCCs. In an effort to evaluate the long-term outcome of patients treated with imiquimod for BCC, we conducted a 5-year follow-up, prospective, open-label study.
The sample size was 55 BCCs, and the cases were assigned to 2 groups consecutively: 35 BCCs were treated 3 times weekly for 8 weeks, and 20 BCCs were treated 5 times weekly for 5 weeks. Inclusion criteria were age 18 years or older; primary BCC larger than 8 mm; and a superficial, nodular, or infiltrative histologic pattern.1 Exclusion criteria were pregnancy; immunosuppression; and genetic predisposition to BCC and other histologic subtypes of BCC. Diagnosis was verified on histologic findings in 1 biopsy specimen prior to treatment.
All patients applied 24 doses of imiquimod (Aldara, 3M Pharmaceuticals, St Paul, Minn) to the BCC lesion at night without occlusion. A 4-mm punch biopsy specimen was taken during the first 3 weeks of therapy to study the mechanism of action of imiquimod in BCC,2 and a final biopsy specimen was obtained 6 weeks after treatment to assess clearance of BCC. Patients whose BCCs had cleared after treatment were visited regularly for 5 years. The main outcome measures of the study were the intent-to-treat long-term clearance rate and the recurrence rate of the imiquimod-treated BCCs. We used the t test, χ2 test, Fisher exact test, and multivariate analyses in our statistical analysis (SPSS, version 11.5; SPSS Inc, Chicago, Ill).
Fifty patients with a total of 4 superficial, 8 nodular, and 43 infiltrative BCCs (n = 55) were enrolled in 2001. The clinical and tumor characteristics are summarized in the Table, and subject disposition during the study is shown in Figure 1.
Forty-two treated BCCs (76%) showed no clinical sign of tumor or histologic tumor signs in the 6-week posttreatment biopsy specimen; all of these patients were observed periodically for a mean of 53 months (range, 10-61 months). During this period, 1 patient died; 4 patients were lost to follow-up with no sign of recurrence at their last visit; and a 76-year-old woman developed a recurrent infiltrative BCC after 10 months of follow-up. Late relapses did not occur, and the 5-year recurrence rate was only 2% (1 of 37). None of the remaining 36 BCCs recurred after a mean of 58 months of follow-up (range, 49-61 months).
The cosmetic results were excellent in 33% of cases (n = 24), but a permanent hypopigmented macule was observed in 67% of cases (n = 12) (Figure 2). For the intent-to-treat data set, the long-term clearance rate for imiquimod was 65% for all BCCs (n = 36), 100% for superficial BCCs (n = 4), 75% for nodular BCCs (n = 6), 60% for infiltrative BCCs (n = 26), and 65% for both dosing regimens (n = 23 and n = 13). Multivariate analysis demonstrated that only baseline BCC size had a significant association with long-term clearance (P = .02) (odds ratio, 0.99; 95% confidence interval, 0.98-0.10): the smaller the tumor, the higher the chance to be cured with imiquimod.
To our knowledge, this is the first follow-up study examining topical imiquimod for the treatment of BCCs. Our long-term clearance rates of superficial and nodular BCCs are similar to the short-term rates found in randomized controlled trials, which range from 69% to 100% for superficial BCC3-8 and 42% to 76% for nodular BCC.8,9 Moreover, 60% of infiltrative BCCs in the present study did not recur by the end of the study.
However, the comparison of our results with those of previously reported studies is complicated owing to differences in patient and tumor selection, dosing regimens, number of biopsies performed, and follow-up times. Our results may be biased by the biopsy specimens taken during treatment, which could have removed tumor mass, increased imiquimod absorption, and/or induced a host immunologic reaction resulting in tumor regression.
Nonetheless, our cases were treated with 24 doses of imiquimod on 2 dosing schedules. Imiquimod is approved for 5-times-a-week dosing for 6 weeks (30 doses) for superficial BCC. Surprisingly, only 1 recurrence (2%) was found. Imiquimod treatment provided long-term clinical benefit in 36 (86%) of the 42 BCCs initially cleared.
An ongoing 5-year study is currently being conducted in Europe to monitor possible recurrences of superficial BCC following successful treatment with imiquimod.10 This study has enrolled patients with a total of 162 BCCs, and the interim 2-year results have shown 14 recurrences (recurrence rate of 8%), but this does not include a histologic assessment after therapy, as we did.
In conclusion, our data suggest that imiquimod treatment is effective in most cases of noninfiltrative BCCs, but more trials are required to determine the therapeutic role of imiquimod for infiltrative BCCs, either alone or in combination with other therapies.
Correspondence: Dr Vidal, Hospital Dos de Maig, Department of Dermatology, Dos de Maig 301, Barcelona 08025, Spain (firstname.lastname@example.org).
Financial Disclosure: Drs Vidal and Alomar have served as paid speakers for 3M Pharmaceuticals. Dr Alomar has also served as investigator and consultant to 3M Pharmaceuticals.
Acknowledgment: We appreciate the expert statistical assistance of Ignasi Gich, MD, PhD.