Imiquimod 5% Cream as an Adjunctive
Therapy for Primary Nodular Nasal Basal
Cell Carcinomas Prior to Mohs Surgery: A
Randomized, Vehicle-Controlled, DoubleBlind Study
Palak Parekh, MD
David F. Butler, MD
Disclosures
• Investigator initiated study
• Grant from 3M and Graceway
pharmaceuticals
• Grant from Scott and White Education and
Research Division
Scott and White Clinic
Temple, Texas
Imiquimod for BCC
Imiquimod: Mechanism of Action
•
•
•
•
•
Immune response modifier
Stimulates Toll-like receptors 7 and 8
Induces IFN-α, IL-1, -6, -8, -10, -12, TNF-α
Recruits inflammatory cells
Increased expression of Notch 1 and Fas
receptor on BCCs
• Decreased expression of bcl-2
• 2004 FDA approval for superficial BCCs
on trunk and extremities
• Applied 5x per week for 6 weeks
• Histologic cures: 82% (5x per week)
79% (7x per week)
(Giesse J et al.)
Imiquimod for Nodular BCCs
Nodular BCC
Studies have shown:
Study
• Clearance rates less for nodular BCCs
(65-76%) than superficial BCCs
• Clearance dependent on frequency and
duration of treatment
• Studies not confined to the face
• Histologic confirmation often lacking
Sterry
Eigentler
Peris
Shumack
Frequency Duration
3x/week
3x/week
3x/week
3x/week
5x/week
7x/week
6 weeks
8 weeks
12 weeks
12 weeks
12 weeks
12 weeks
Clearance
65%
64%(histo)
52.6%
60%
70%
76%
1
Nasal BCCs
•
•
•
•
•
Most common site for BCC (25-30%)
Cosmetically important
Indication for Mohs surgery
Surgical defects often require flap or graft
Imiquimod could be used as adjunctive
therapy in combination with surgery
Hypothesis
Nightly application of imiquimod 5% cream
with occlusion for 6 weeks prior to Mohs
surgery should reduce the number of
stages required, size of the defect, and
cost of Mohs surgery and wound repair for
primary nodular basal cell carcinomas of
the nose.
Study Design
Study Characteristics
• Prospective, randomized, double-blind, vehiclecontrolled study
• Adults, non-pregnant, immunocompetent
• Primary nodular nasal basal cell carcinoma
• < 1cm in size
• 2 mm punch biopsy histological confirmation
• Nightly application of vehicle or imiquimod 5%
cream for 6 weeks
• Covered with small band-aid
• Mohs surgery performed 10 weeks after starting
study (4 weeks off treatment prior to Mohs)
• 31 patients entered study
• 28 patients completed study
• 3 in Imiquimod group discontinued study: 2 local
adverse events, 1 other illness
• Vehicle: 16 patients: 9 male, 7 female
age: 75.31 + 11.38
• Imiquimod: 12 patients: 8 male, 4 female
age: 73.27 + 10.53
• No significant difference in baseline
characteristics.
Adverse Events
Primary and Secondary Outcomes
• Number of Mohs stages for clear margins
• If 1st stage clear, presence or absence of
tumor in block (# of complete responders)
• Surgical defect size
• Cost of Mohs stages in RVUs
• Cost of wound repair in RVUs
Vehicle
(n=16)
Local Adverse event
(redness, blisters,
erosions, crusting)
Systemic symptoms
(flu-like symptoms)
Pain
3wk
4
6wk
2
(p=.0005)
1(nausea)
0
Imiquimod
(n=13)
10
10
0
1
2
Study Outcome
Vehicle
(n=16)
Study Outcome
Imiquimod
(n=12)
ITT
(n=15)
11 (68.8%)
11 (91.7%)
11 (73.3%)
5 (31.3%)
1 (8.3%)
4 (26.7%)
(p=0.20)
(p=1.0)
Number of Mohs stages:
One stage only
Two stages
Vehicle Imiquimod
(n=11) (n=11)
yes
Study Outcome
Defect size:
(mean)
Presence of tumor
in block if first stage
had clear margins:
Vehicle
100.30 mm sq.
+ 41.90
9 (81.2%) 6 (54.55%)
no
2 (18.18%) 5 (45.45%)
(P=0.36)
6 cases with residual carcinoma in imiquimod arm added to
1 case requiring second stage = 7/12 (58.3%) cases had
persistent tumor. Thus, only 5/12 (41.7%) in imiquimod
arm were “complete responders.”
Study Outcome
Imiquimod
88.47 mm sq.
+ 27.82
Vehicle
(n=16)
Cost of Mohs surgery
in RVUs:
Imiquimod
(n=12)
8.45
7.83
+ 1.28
+ 0.82
(p=0.70)
(p=0.12)
Study Outcome
Vehicle
(n=16)
Cost of wound
repair in RVUs:
8.59
+ 2.96
( p=0.62)
Conclusions
Imiquimod
(n=12)
8.47
+ 3.39
• Our study did not demonstrate a statistically significant
difference in the number of Mohs stages, size of the
mean surgical defect, and cost of Mohs surgery and
reconstructive repair between the treatment and vehicle
group.
• Limitation of our study was small sample size. Sample
size of 56 would have been needed for sufficient power
to demonstrate statistically significant difference.
• A larger study with possibly varied histologic types of
basal cell carcinomas may aid in demonstration of
statistical significance.
3
Bibliography
Conclusions
• The low percentage of histologic “complete responders”
(42%) compared to previous studies on superficial BCCs
(79-82%) warrants caution when using imiquimod as a
single modality for treatment of nodular BCCs on the
nose.
• Local inflammatory reactions associated with imiquimod
may limit its usefulness as an adjunctive treatment.
1.
Geisse JK, Rich P, Pandya A, et al. Imiquimod 5% cream for the treatment of
superficial basal cell carcinoma: a double-blind, randomized, vehicle-controlled
study. J Am Acad Dermatol. 2002 47(3): 390-398.
2.
Sterry W, Ruzicka T, Herrera E, et al. Imiquimod 5% cream for the treatment of
superficial and nodular basal cell carcinomas: randomized studies comparing lowfrequency dosing with and without occlusion. Br J Dermatol. 2002; 147: 12271236.
3.
Peris K, Campione E, Micantonio T, et al. Imiquimod treatment of superficial and
nodular basal cell carcinoma: 12-week open-label trial. Dermatol Surg. 2005;
31(3): 318-323.
4.
Shumack S, Robinson J, Kossard S, et al. Efficacy of topical 5% imiquimod cream
for the treatment of nodular basal cell carcinoma. Arch Dermatol. 2002;
138(9): 1165-1171.
5.
Eigentler TK, Kamin A, Weide BM, et al. A phase III, randomized, open label
study to evaluate the safety and efficacy of imiquimod 5% cream applied thrice
weekly for 8 and 12 weeks in the treatment of low-risk nodular basal cell
carcinoma. J Am Acad Dermatol. 2007; 57(4): 616-621.
6.
Torres A, Niemeyer A, Berkes B, et al. 5% imiquimod cream and reflectancemode confocal microscopy as adjunct modalities to mohs micrographic surgery for
treatment of basal cell carcinoma. Dermatol Surg. 2004; 30(12 pt 1): 1462-1469.
7.
Huber A, Huber JD, Skinner RB Jr, et al. Topical imiquimod treatment for nodular
basal cell carcinomas: an open-label series. Dermatol Surg. 2004; 30(3): 429430
4