Pharmacotherapy Update: Long-Term Follow-Up of Topical Imiquimod Cycle Therapy - By James Q. Del Rosso, D.O., F.A.O.C.D. Managing actinic keratosis of the scalp and squamous cell carcinoma in situ of the scalp and face. Topical imiquimod 5% cream (Aldara) has been efficacious for treating actinic keratosis (AK) using a variety of treatment regimens, including cycle therapy. Cycle therapy is defined as imiquimod 5% cream three times per week for 4 weeks on, followed by 4 weeks off treatment (single cycle). Cycles may be repeated based on therapeutic response. This article evaluates long-term follow-up after imiquimod cycle therapy used in 22 patients with diffuse AK of the scalp and six patients with squamous cell carcinoma (SCC) in situ of the scalp or face. The follow-up ranged from 12 to 36 months (average 20 months). Implications regarding patient selection, optimal application technique, and adjustments in use based on response patterns are discussed. Background Actinic Keratosis. Application of topical imiquimod 5% cream two to three times per week has produced complete clearance of AKs in 45% to 84 % of cases; many patients not exhibiting complete clearance demonstrated >75% lesion reduction.1,2 A pilot evaluation of “cycle therapy” for AK involving scalp, cheeks, forehead and temples evaluated topical imiquimod applied three times per week for 4 weeks followed by a 4-week rest period (single cycle).3 A second cycle was used if residual AKs were observed. A single cycle produced complete clearance in 46% of the treated cosmetic units; an additional 36% of cosmetic units cleared completely after a second cycle. Squamous Cell Carcinoma in situ. A study evaluating topical imiquimod 5% cream applied once daily for up to 16 weeks for SCC in situ (>90% on legs/lesion size 1 cm to 5.4 cm) confirmed a 93% cure rate; post-treatment biopsy was performed after 6 weeks and clinical follow-up completed over 6 months.4 In six patients who developed brisk inflammation, complete clearance occurred after 4 to 8 weeks of imiquimod. Published case reports have documented efficacy with imiquimod application three times per week for durations ranging from 9 to 17 weeks; post-treatment follow-ups have indicated no evidence of recurrence over 12 to 15 months.5,6 Penile SCC in situ treated with topical imiquimod every second day for 9 to 16 weeks demonstrated complete clearance confirmed by post-treatment biopsy and clinical evaluation over 3 months in one patient and 12 months in four patients.7 Imiquimod therapy for SCC in situ may be initiated at a frequency of three applications per week.1 Frequency and duration of therapy may be adjusted based on clinical response and intensity of inflammation.1,4 Current Report Reported here are data on long-term responses to topical imiquimod “cycle” therapy in 22 patients treated for AK of the scalp and six patients treated for SCC in situ of the scalp (n=3) or face (n=3/nose dorsum-1, temple-2). The mean number of baseline AKs on the scalp was 16 lesions (range 12 to 23). The diameters for scalp SCC in situ lesions were 1.8 cm, 2.4 cm and 2.6 cm. The SCC in situ of the face measured 1.1 cm (nose dorsum) and 1.6 cm and 1.8 cm (temple). All 22 patients with AK of the scalp included in this long-term assessment had cleared completely after use of topical imiquimod 5% cream, 10 after a single cycle and 12 after a second cycle. The six patients with SCC in situ of the scalp or face cleared after obligatory use of two cycles of topical imiquimod 5% cream. The follow-up duration ranged from 12 to 36 months (average 20 months). Long-Term Results After initial clearance was determined by clinical assessment for AK (after one or two cycles) or for SCC in situ (two cycles), patients were followed every 2 to 4 months thereafter. At the point where new AKs were noted, patients were not retreated with topical imiquimod. Instead, cryotherapy was used for visible AKs so that patients could be followed longer to determine the duration of >75% AK lesion clearance. All six patients treated for SCC in situ remained completely clear over the entire duration of follow-up (range 18 to 28 months).   Summary • Topical imiquimod cycle therapy has been effective for treating AKs and for patients with SCC in situ. • Mean duration of complete AK lesion clearance after one cycle was 13.1 months — 18 months after two cycles. • The mean duration of at least 75% lesion clearance based on follow-up was 18 months after a single cycle and 24.5 months after two cycles. • Complete clearance of all six squamous cell carcinoma in situ lesions on the scalp (n=3) and face (n=3) was sustained over the entire course of follow-up (16 to 28 months).   References 1. Del Rosso JQ. Therapy for cutaneous epithelial malignancy: a review of research, development, current status and practical use of topical imiquimod. Skin & Aging. 2003;11:44-54. 2. Stockfleth. Christophers E, Benninghoff B, et al. Low incidence of new actinic keratoses after topical 5 % imiquimod cream treatment: a long-term follow-up study. Arch Dermatol. 2004;140:1542. 3. Salasche S, Levine N, Morrison L. Cycle therapy of actinic keratoses of the face and scalp with 5 % topical imiquimod: an open label trial. J Am Acad Dermatol; 2002;47:571-577. 4. Mackenzie-Wood A, Kossard S, De Launey J, et al. Imiquimod 5 % cream in the treatment of Bowen’s disease. J Am Acad Dermatol. 2001;44:462-470. 5. Orengo I, Rosen T, Guill CK. Treatment of squamous cell carcinoma in situ of the penis with 5% imiquimod cream: a case report. J Am Acad Dermatol. 2002;47:S225-228. 6. Hengee UR, Stark R. Topical imiquimod to treat in-traepidermal carcinoma. Arch Dermatol. 2001;137:709-711. 7. Arlette JP. Treatment of Bowen’s disease and erythroplasia of Queyrat. Br J Dermatol. 2003;149 (Suppl 66):43-47. Skin & Aging - ISSN: 1096-0120 - Volume 14 - Issue 11 - November 2006 - Pages: 48 - 49