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Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from two phase III, randomized, vehicle-controlled studies

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Abstract

Background

Imiquimod is an immune response modifier that is a Toll-like receptor 7 agonist that induces interferon and other cytokines through the innate immune system and stimulates cell-mediated immunity through T cells. Imiquimod has been shown to be efficacious as a topical treatment for basal cell carcinoma (BCC).

Objective

We sought to evaluate the efficacy and safety of imiquimod 5% cream compared with vehicle for treating superficial BCC (sBCC).

Methods

Two identical studies were conducted. Subjects with one sBCC were dosed with imiquimod or vehicle cream once daily 5 or 7×/week for 6 weeks in these 2 randomized, double-blind, vehicle-controlled Phase III studies. The lesion site was clinically examined 12 weeks posttreatment and then excised for histological evaluation.

Results

Data from both studies were pooled. Composite clearance rates (combined clinical and histological assessments) for the 5 and 7×/week imiquimod groups were 75% and 73%, respectively. Histological clearance rates for the 5 and 7×/week imiquimod groups were 82% and 79%, respectively. Increasing severity of erythema, erosion, and scabbing/crusting was associated with higher clearance rates.

Conclusion

Imiquimod appears to be safe and effective for the treatment of sBCC when compared with vehicle cream. The difference in clearance rates between the two imiquimod dosing groups was not significant. The 5×/week regimen is recommended.

Section snippets

Methods

Two identical, multicenter, randomized, double-blind, vehicle-controlled, dose-response studies were initiated at 55 centers in the United States. All protocols and informed consent documents were submitted to and approved by each study center's institutional review board. Before study procedures were initiated, each subject voluntarily signed an informed consent form.

Subject disposition and demographics

A total of 724 subjects were enrolled into the combined studies. Thirty-two subjects discontinued during the treatment period and 13 subjects discontinued from the posttreatment period. One of these subjects discontinued from the treatment period, went on to the posttreatment period, and subsequently discontinued from the posttreatment period. Fig 1 displays subject disposition during the study.

In the ITT group, 279 (39%) subjects were female and 445 (61%) were male. The subject population

Clearance rates

Based on the ITT population, the composite clearance rates for the 5×/week and 7×/week imiquimod groups were 75% (95% CI: 68-81%) and 73% (95% CI: 66-79%), respectively (Fig 2). A total of 32 subjects were considered nonresponders due to either a missing endpoint assessment (26 subjects) or who were inadvertantly entered into the study without a histologic diagnosis of sBCC (6 subjects). Clearance rates based solely on histology data for the 5×/week and 7×/week imiquimod groups were somewhat

Adverse events

The incidence of AEs during the treatment period was higher than during the posttreatment period. During the treatment period, 58% of subjects in the 5×/week imiquimod group and 64% of subjects in the 7×/week imiquimod group and 36% of subjects in the combined vehicle groups experienced at least 1 adverse event. The proportion of subjects in the 5×/week and 7×/week vehicle groups who reported at least 1 AE during the posttreatment period were 33% and 31%, respectively. A total of 7 (4%)

Discussion

The results from these Phase III studies confirm that imiquimod has higher complete clearance rates than vehicle cream for each of the active treatment groups. Additionally, there was not a statistically significant or clinically meaningful difference in complete clearance rate noted between the imiquimod 5×/week (75% composite and 82% histologic) and 7×/week (73% composite and 79% histologic) treatment groups.

Although the studies were blinded, LSRs were most frequently observed with the active

Acknowledgements

Investigators who enrolled subjects in the 1393-IMIQ study: M. Brown, MD, University of Rochester, Rochester, NY; I. Caro, MD, Massachusetts General Hospital, Harvard Medical School, Boston, MA; S. Davis, MD, Dermatology Clinical Research Center of San Antonio, San Antonio, TX; C. Elmets, MD, University of Alabama, Birmingham, AL; P. H. Ely, MD, University of California-Davis, Grass Valley, CA; K. Fang, MD, University of California-Davis, VA Hospital, Martinez, CA; K. Gross, MD, Skin Surgery

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    Citation Excerpt :

    A summary of the outcomes from eligible studies is shown in Table 1. In the two eligible RCTs38,39 comparing topical 5% imiquimod with placebo for clinically diagnosed superficial BCCs, outcomes assessed included histological clearance rates at 6 weeks following the end of treatment and adverse events during treatment. Depending on the frequency of cream administration, histological clearance rates ranged from 51.7-100% for those treated with 5% imiquimod and from 2.0-18.8% for individuals in the placebo (i.e. observational) group.

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The two studies reported in this manuscript were funded by 3M Pharmaceuticals, St. Paul, Minn.

Disclosure: Drs Geisse, Caro, Lindholm, and Golitz have been compensated by 3M Pharmaceuticals for their services in conducting the studies reported here. Dr Owens and Ms Stampone are employees of 3M Pharmaceuticals.

Results from these studies have been presented at the congress of the American Academy of Dermatology, San Francisco, CA (March 2003), World Congress on Cancers of the Skin, Seville, Spain (May 2003), ASDS-ACMMSCO Combined Annual Meeting, New Orleans, La (October 2003), and the European Academy of Dermatology and Venereology, Barcelona, Spain (October 2003).

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