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Comparison of topical methylaminolevulinate photodynamic therapy versus placebo photodynamic therapy in nodular basal cell carcinoma1
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IMIQUIMOD 5% CREAM EFFECTIVE IN THE TREATMENT OF LARGE SUPERFICIAL BCC Stephen Shumack, MBBS, St George Dermatology, Kogarah, Australia, Kurt Gebauer, MBBS, Fremantle Dermatology, Fremantle, Australia, Ken Macdonald, MBBS, Dermatology Practice, Christchurch, New Zealand, Mark Amies, MBBS, 3M Pharmaceuticals, Sydney, Australia Background: Imiquimod has been shown to be safe and effective as a topical treatment for typical size (⬍2 cm maximum diameter) superficial basal cell carcinomas (sBCCs). Objective: To evaluate the efficacy, safety and cosmetic outcome of imiquimod 5% cream for the treatment of large sBCCs. Methods: This was an open-label, multicenter phase II study conducted in Australia and New Zealand. Subjects applied imiquimod 5⫻/week for 6 weeks to a biopsy-confirmed sBCC measuring ⱖ2 cm in at least one dimension. At 12 weeks posttreatment, the tumor treatment site was examined clinically for remaining sBCC followed by multiple biopsies (if clinically clear) or excisions (if clinically not clear) and examined histologically. Complete response rate was defined as the proportion of subjects at 12-weeks posttreatment with no clinical and no histological evidence of sBCC at the target tumor site. Local skin reactions (LSRs) were assessed at all study visits. Skin quality parameters were rated for the treatment site and the anatomically opposite area to judge cosmetic outcome. Results: Sixty-six subjects entered with lesions ranging between 2-48 cm2. The complete response rate was 55/66 (83%) and 4 of 5 subjects who did not have clinical clearance of sBCC had reductions in tumor size of 13%-99%. Subgroup analysis indicated that as severity of edema, erosion and ulceration increased, so did the clearance rate. The most frequently reported adverse event was application site reaction. LSRs and application site reactions improved and resolved after cessation of treatment: only 1 subject withdrew due to LSRs. Small mean differences were seen in skin quality parameter scores between treated tumor sites and anatomically opposite areas 12 weeks posttreatment. Conclusion: Imiquimod 5% cream applied 5⫻/week is an effective therapy for the clearance of large sBCC, having an acceptable safety profile and satisfactory cosmetic outcome. References: 1. Ashby MA, Smith J, Ainslie J, McEwan L. Treatment of nonmelanoma skin cancer at a large Australian centre. Cancer. 1989;63:1863-1871. 2. Hemmi H, Kaisho T, Takeuchi O, et al. Small antiviral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3:196200.
MULTIPLE BASAL-CELL CARCINOMAS ASSOCIATED WITH A PORT WINE STAIN Christine D Ambro, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States, Jason Lee, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States, Paul Bujanauskas, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States We present a case of an 81-year-old man who presented with multiple basal-cell carcinomas (BCC) confined to his Port Wine Stain (PWS) He denied any previous treatment to this area. His past medical history included squamous cell carcinoma of the right false vocal cord treated with surgical excision and 7 weeks of XRT in 1999. The radiation field was restricted to the right neck and did not involve the face or scalp. He also had a BCC on his scalp treated with excision in September of 1998. On examination, three lesions were noted within the PWS. One lesion on the left zygoma and one lesion on the glabella were red, papules with central atrophy and pearly borders. The last lesion, located on the left nasal ala, was a red atrophy macule. All lesions were located exclusively within the PWS, not involving surrounding skin. Biopsies were performed confirming BCC. The development of BCC in a PWS is rare and had been reported only several times over the past fifty years. The etiology of these malignancies in this situation continues to be debated. Decades ago it was common practice to treat PWS with the use of topical thorium X, a source of a-radiation, radium or x-rays. It has been suggested that this may be the etiologic factor in the development of malignancy. However, Sarkany and Caron have disputed this theory, sighting that a-ray is associated with a low carcinogenic risk. Furthermore, Moharjerin did not observe untoward sequelae after thorium treatment in thirty-nine patients with PWS over a twenty-five year period, suggesting that BCC could evolve spontaneously. Additionally, four cases of BCC complicating a PWS without prior treatment with ionizing radiation have been published in the literature. This suggests that the ectatic vessels may produce an oncogenic factor, or make the overlying epidermis more susceptible to ultraviolet radiation or the use of thorium X. Disclosure not available at press time.
Authors are study investigators paid by 3M Pharmaceuticals or employees of 3M Pharmaceuticals. 100% is sponsored by 3M Pharmaceuticals.
P477
P475 IMIQUIMID 5% CREAM DOSED 3 TIMES WEEKLY FOR THE TREATMENT OF ACTINIC KERATOSIS Neil J. Korman, MD, PhD, Case Western Reserve University, Cleveland, OH, United States, Mark Ling, MD, PhD, Medaphase, Newnan, GA, United States, Robert Matheson, MD, Oregon Medical Research Center, Portland, OR, United States, Stacy Smith, MD, Therapeutics Inc., La Jolla, CA, United States Imiquimod 5% cream is an immune response modifier that works by enhancing the innate and adaptive immune responses. Since imiquimod can induce strong immune responses that vary depending on intrinsic and extrinsic factors, infrequent dosing for an extended duration was evaluated. Two large, randomized, vehicle controlled studies were conducted to determine if imiquimod 5% cream dosed 3 times weekly for 16 weeks was a safe and effective treatment for actinic keratosis. Overall, 492 patients from 26 clinical sites applied study cream to a contiguous 25-cm2-treatment area containing 4 to 8 AK lesions on the face or balding scalp (not both). Patients were randomized in a 1 to 1 ratio. The combined data indicated that imiquimod was statistically significantly better than vehicle with respect to both complete clearance rate (48.3% vs 7.2%, p ⬍ 0.0001), defined as the proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area, and partial clearance rate (64.0% vs. 13.6%, p ⬍ 0.0001), defined as the proportion of patients at the 8-week posttreatment visit with at least a 75% reduction in the number of AK lesions counted at baseline in the treatment area. A complete clearance rate of 57% for another large, randomized, vehicle-controlled study with histology suggests the complete clearance rate for 3-times weekly dosing may be closer to 60%. The combined safety profile was acceptable. The results indicate that 3 times per week dosing with imiquimod 5% cream is a safe and effective treatment for actinic keratosis. All authors are either study investigators given clinical study grants by 3M Pharmaceuticals or employees of 3M Pharmaceuticals. The cost of the poster was sponsored by 3M Pharmaceuticals
MARCH 2004
COMPARISON OF TOPICAL METHYLAMINOLEVULINATE PHOTODYNAMIC THERAPY VERSUS PLACEBO PHOTODYNAMIC THERAPY IN NODULAR BASAL CELL CARCINOMA Whitney D Tope, MD, University of California, San Franciso, CA, United States, A Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States, RA El-Azhary, MD, Mayo Clinic, Rochester, MN, United States, NJ Lowe, MD, Clinical Research Specialists Inc, Santa Monica, CA, United States Objective: To investigate the efficacy, safety, and cosmetic outcome of MAL PDT versus placebo PDT in nodular BCC. Methods: Nodular BCCs were treated in a multi-center, randomized, double-blind, placebo-controlled comparison. 41 BCC in 33 subjects received 2 cycles (1 week apart) of MAL PDT. 39 BCC in 32 subjects received 2 cycles of placebo cream PDT. Surface debridement and slight lesion debulking were done prior to cream application. BCC with a partial clinical response at 3 months were re-treated. BCC manifesting complete clinical response (CCR) at 6 months after last treatment were excised to determine the complete histologic response (CHR). All subjects and treatment sites were evaluated for adverse events, cosmetic outcome and patient satisfaction. Results: MAL PDT was superior to placebo PDT (p ⬍ 0.001). The overall lesion CCR was 80% (33/41) for MALPDT versus 51% (20/39) for placebo PDT. The overall lesion CHR was 78% (32/41) for MAL PDT versus 33% (13/39) for placebo PDT. Among sites showing CCR investigator-assessed cosmetic outcome was excellent or good in 93% of MAL PDT sites versus 90% for placebo PDT sites. Patient satisfaction compared to prior treatment methods was better in 60% of MAL PDT treated sites and 52% of placebo PDT sites. No systemic adverse reactions occurred in either treatment group. Local AE’s were common, with 91% in the MAL PDT group and 75% in the placebo group. Mild to moderate erythema, burning, stinging, and pain occurred in both groups. Median duration of pain was 2 days after MAL PDT versus 3-6 days after placebo PDT. All serious AE’s in both groups were unrelated to treatment. Conclusions: MAL PDT was clinically and histologically superior to placebo PDT in treating nodular BCC, both with prior lesion preparation. Expected transient local reactions of mild to moderate severity occurred in both groups. Disclosure not available at press time.
J AM ACAD DERMATOL
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P476
IMIQUIMOD 5% CREAM EFFECTIVE IN THE TREATMENT OF LARGE SUPERFICIAL BCC Stephen Shumack, MBBS, St George Dermatology, Kogarah, Australia, Kurt Gebauer, MBBS, Fremantle Dermatology, Fremantle, Australia, Ken Macdonald, MBBS, Dermatology Practice, Christchurch, New Zealand, Mark Amies, MBBS, 3M Pharmaceuticals, Sydney, Australia Background: Imiquimod has been shown to be safe and effective as a topical treatment for typical size (⬍2 cm maximum diameter) superficial basal cell carcinomas (sBCCs). Objective: To evaluate the efficacy, safety and cosmetic outcome of imiquimod 5% cream for the treatment of large sBCCs. Methods: This was an open-label, multicenter phase II study conducted in Australia and New Zealand. Subjects applied imiquimod 5⫻/week for 6 weeks to a biopsy-confirmed sBCC measuring ⱖ2 cm in at least one dimension. At 12 weeks posttreatment, the tumor treatment site was examined clinically for remaining sBCC followed by multiple biopsies (if clinically clear) or excisions (if clinically not clear) and examined histologically. Complete response rate was defined as the proportion of subjects at 12-weeks posttreatment with no clinical and no histological evidence of sBCC at the target tumor site. Local skin reactions (LSRs) were assessed at all study visits. Skin quality parameters were rated for the treatment site and the anatomically opposite area to judge cosmetic outcome. Results: Sixty-six subjects entered with lesions ranging between 2-48 cm2. The complete response rate was 55/66 (83%) and 4 of 5 subjects who did not have clinical clearance of sBCC had reductions in tumor size of 13%-99%. Subgroup analysis indicated that as severity of edema, erosion and ulceration increased, so did the clearance rate. The most frequently reported adverse event was application site reaction. LSRs and application site reactions improved and resolved after cessation of treatment: only 1 subject withdrew due to LSRs. Small mean differences were seen in skin quality parameter scores between treated tumor sites and anatomically opposite areas 12 weeks posttreatment. Conclusion: Imiquimod 5% cream applied 5⫻/week is an effective therapy for the clearance of large sBCC, having an acceptable safety profile and satisfactory cosmetic outcome. References: 1. Ashby MA, Smith J, Ainslie J, McEwan L. Treatment of nonmelanoma skin cancer at a large Australian centre. Cancer. 1989;63:1863-1871. 2. Hemmi H, Kaisho T, Takeuchi O, et al. Small antiviral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol. 2002;3:196200.
MULTIPLE BASAL-CELL CARCINOMAS ASSOCIATED WITH A PORT WINE STAIN Christine D Ambro, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States, Jason Lee, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States, Paul Bujanauskas, MD, Jefferson Medical College, Department of Dermatology and Cutaneous Biology, Philadelphia, PA, United States We present a case of an 81-year-old man who presented with multiple basal-cell carcinomas (BCC) confined to his Port Wine Stain (PWS) He denied any previous treatment to this area. His past medical history included squamous cell carcinoma of the right false vocal cord treated with surgical excision and 7 weeks of XRT in 1999. The radiation field was restricted to the right neck and did not involve the face or scalp. He also had a BCC on his scalp treated with excision in September of 1998. On examination, three lesions were noted within the PWS. One lesion on the left zygoma and one lesion on the glabella were red, papules with central atrophy and pearly borders. The last lesion, located on the left nasal ala, was a red atrophy macule. All lesions were located exclusively within the PWS, not involving surrounding skin. Biopsies were performed confirming BCC. The development of BCC in a PWS is rare and had been reported only several times over the past fifty years. The etiology of these malignancies in this situation continues to be debated. Decades ago it was common practice to treat PWS with the use of topical thorium X, a source of a-radiation, radium or x-rays. It has been suggested that this may be the etiologic factor in the development of malignancy. However, Sarkany and Caron have disputed this theory, sighting that a-ray is associated with a low carcinogenic risk. Furthermore, Moharjerin did not observe untoward sequelae after thorium treatment in thirty-nine patients with PWS over a twenty-five year period, suggesting that BCC could evolve spontaneously. Additionally, four cases of BCC complicating a PWS without prior treatment with ionizing radiation have been published in the literature. This suggests that the ectatic vessels may produce an oncogenic factor, or make the overlying epidermis more susceptible to ultraviolet radiation or the use of thorium X. Disclosure not available at press time.
Authors are study investigators paid by 3M Pharmaceuticals or employees of 3M Pharmaceuticals. 100% is sponsored by 3M Pharmaceuticals.
P477
P475 IMIQUIMID 5% CREAM DOSED 3 TIMES WEEKLY FOR THE TREATMENT OF ACTINIC KERATOSIS Neil J. Korman, MD, PhD, Case Western Reserve University, Cleveland, OH, United States, Mark Ling, MD, PhD, Medaphase, Newnan, GA, United States, Robert Matheson, MD, Oregon Medical Research Center, Portland, OR, United States, Stacy Smith, MD, Therapeutics Inc., La Jolla, CA, United States Imiquimod 5% cream is an immune response modifier that works by enhancing the innate and adaptive immune responses. Since imiquimod can induce strong immune responses that vary depending on intrinsic and extrinsic factors, infrequent dosing for an extended duration was evaluated. Two large, randomized, vehicle controlled studies were conducted to determine if imiquimod 5% cream dosed 3 times weekly for 16 weeks was a safe and effective treatment for actinic keratosis. Overall, 492 patients from 26 clinical sites applied study cream to a contiguous 25-cm2-treatment area containing 4 to 8 AK lesions on the face or balding scalp (not both). Patients were randomized in a 1 to 1 ratio. The combined data indicated that imiquimod was statistically significantly better than vehicle with respect to both complete clearance rate (48.3% vs 7.2%, p ⬍ 0.0001), defined as the proportion of patients at the 8-week posttreatment visit with no clinically visible AK lesions in the treatment area, and partial clearance rate (64.0% vs. 13.6%, p ⬍ 0.0001), defined as the proportion of patients at the 8-week posttreatment visit with at least a 75% reduction in the number of AK lesions counted at baseline in the treatment area. A complete clearance rate of 57% for another large, randomized, vehicle-controlled study with histology suggests the complete clearance rate for 3-times weekly dosing may be closer to 60%. The combined safety profile was acceptable. The results indicate that 3 times per week dosing with imiquimod 5% cream is a safe and effective treatment for actinic keratosis. All authors are either study investigators given clinical study grants by 3M Pharmaceuticals or employees of 3M Pharmaceuticals. The cost of the poster was sponsored by 3M Pharmaceuticals
MARCH 2004
COMPARISON OF TOPICAL METHYLAMINOLEVULINATE PHOTODYNAMIC THERAPY VERSUS PLACEBO PHOTODYNAMIC THERAPY IN NODULAR BASAL CELL CARCINOMA Whitney D Tope, MD, University of California, San Franciso, CA, United States, A Menter, MD, Texas Dermatology Research Institute, Dallas, TX, United States, RA El-Azhary, MD, Mayo Clinic, Rochester, MN, United States, NJ Lowe, MD, Clinical Research Specialists Inc, Santa Monica, CA, United States Objective: To investigate the efficacy, safety, and cosmetic outcome of MAL PDT versus placebo PDT in nodular BCC. Methods: Nodular BCCs were treated in a multi-center, randomized, double-blind, placebo-controlled comparison. 41 BCC in 33 subjects received 2 cycles (1 week apart) of MAL PDT. 39 BCC in 32 subjects received 2 cycles of placebo cream PDT. Surface debridement and slight lesion debulking were done prior to cream application. BCC with a partial clinical response at 3 months were re-treated. BCC manifesting complete clinical response (CCR) at 6 months after last treatment were excised to determine the complete histologic response (CHR). All subjects and treatment sites were evaluated for adverse events, cosmetic outcome and patient satisfaction. Results: MAL PDT was superior to placebo PDT (p ⬍ 0.001). The overall lesion CCR was 80% (33/41) for MALPDT versus 51% (20/39) for placebo PDT. The overall lesion CHR was 78% (32/41) for MAL PDT versus 33% (13/39) for placebo PDT. Among sites showing CCR investigator-assessed cosmetic outcome was excellent or good in 93% of MAL PDT sites versus 90% for placebo PDT sites. Patient satisfaction compared to prior treatment methods was better in 60% of MAL PDT treated sites and 52% of placebo PDT sites. No systemic adverse reactions occurred in either treatment group. Local AE’s were common, with 91% in the MAL PDT group and 75% in the placebo group. Mild to moderate erythema, burning, stinging, and pain occurred in both groups. Median duration of pain was 2 days after MAL PDT versus 3-6 days after placebo PDT. All serious AE’s in both groups were unrelated to treatment. Conclusions: MAL PDT was clinically and histologically superior to placebo PDT in treating nodular BCC, both with prior lesion preparation. Expected transient local reactions of mild to moderate severity occurred in both groups. Disclosure not available at press time.
J AM ACAD DERMATOL
P123