Comparison Between 5-aminolevulinic Acid Photodynamic Therapy Versus Cryotherapy for Actinic Keratosis Treatment

NCT ID: NCT01459393

Last Updated: 2017-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

137 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2011-11-30

Brief Summary

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This study aims to compare in a prospective and randomized way actinic keratosis treatment with 5-aminolevulinic acid photodynamic therapy versus cryotherapy, from the standpoint of therapeutic efficacy, pain, and cosmetic results.

Detailed Description

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Actinic keratosis is a skin lesion induced by chronic sun exposure with a significant prevalence and malignant potential for squamous cell carcinoma, which makes essential its treatment. Today there are several possible therapies, where cryotherapy is usually applied in our practice. Photodynamic therapy (PDT)is another method also widespread for keratosis which involves the administration of a topical precursor drug which produces endogenous photosensitising substances activated by specific light, selectively destroying the diseased tissue. This study aims to evaluate the use the drug formulation for photodynamic therapy 5-aminolevulinic acid (5-ALA) associated with dimethyl sulfoxide, comparing its efficacy with conventional cryotherapy, and also pain and cosmetic results. This project enrolled 137 outpatients from the Department of Cutaneous Oncology of Barretos Cancer Hospital - Pio XII Foundation, with symmetrical and comparable keratosis in their upper limbs. With the same patient as controls, side arm and therapy to be used were randomized: cryotherapy or photodynamic therapy. For cryotherapy was utilized bottles of liquid nitrogen (Cry-ac, 500ml); and for photodynamic therapy was utilized incoherent red light lamp with a total dosis of 37J/cm² . There was one or two sessions of each therapy , at 0 and 3 months; and three assessments for evaluation were done at 0, 3 and 6 months of onset. The evaluations on efficacy were in terms of area regression, and classified as complete response or no response. Pain was assessed by visual analogue scale, and numerical scale. Cosmesis was evaluated with the presence or not, objectively, of hyper, hypopigmentation or scar retraction. Finally, patient's preference regarding utilized therapeutics was noted by the researcher.

Conditions

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Actinic Keratosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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5-ALA Photodynamic Therapy

Topical application of a 2mm of thickness layer of 20% 5-aminolevulinic acid (5-ALA) associated with 20% dimethyl sulfoxide (DMSO) and 3% ethylene diamine acid (EDTA) emulsion, over the actinic keratosis lesion and over a 0,5 cm margin around it. After a 4 hours interval under light protection with plastic film and aluminum foil, the light protection and the emulsion is removed. Then the lesion is lightened with a red (630 nm) incoherent LED lamp AKTILITE CL 128 (PhotoCure ASA, Oslo, Norway) with a total light dose of 37J/cm2.After that dressings are done and kept for 24H, and removed at patient home.

Group Type EXPERIMENTAL

5-ALA Photodynamic Therapy

Intervention Type DRUG

Cryotherapy with liquid nitrogen

Topical application of liquid nitrogen spray (500ml Cry-ac ® bottle) over the actinic keratosis lesion and over a 0,5 cm margin around it during sufficient time to freeze both the lesion and margin.

Group Type ACTIVE_COMPARATOR

Cryotherapy with liquid nitrogen

Intervention Type DRUG

Topical application of liquid nitrogen spray (500ml Cry-ac ® bottle) over the actinic keratosis lesion and over a 0,5 cm margin around it during sufficient time to freeze both the lesion and margin.

Interventions

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5-ALA Photodynamic Therapy

Intervention Type DRUG

Cryotherapy with liquid nitrogen

Topical application of liquid nitrogen spray (500ml Cry-ac ® bottle) over the actinic keratosis lesion and over a 0,5 cm margin around it during sufficient time to freeze both the lesion and margin.

Intervention Type DRUG

Other Intervention Names

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AKTILITE CL 128 (PhotoCure ASA, Oslo, Norway) Cry-ac ®

Eligibility Criteria

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Inclusion Criteria

* Patients older than 18 years.
* Patients with actinic keratoses "symmetrical", ie, comparable in the upper limbs ( with the same grade, I, II or III).
* Patients in accordance with informed consent.

Exclusion Criteria

* Patients with concomitant skin diseases, congenital or acquired (albinism, vitiligo, xeroderma, Gorlin, etc.)
* Immunosuppression (HIV, transplanted patients, etc.)
* Pregnancy or lactation
* Patients who do not agree with the informed consent initially or during the protocol.
* Presence of pigmented lesions near the keratoses.
* Patients with porphyria.
* Patients who have undergone less than 2 months with some kind of treatment for keratosis in the upper limbs.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Barretos Cancer Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Catarina Robert, MD

Role: PRINCIPAL_INVESTIGATOR

Fundação Pio XII - Hospital de Câncer de Barretos

René AC Vieira, PHD

Role: STUDY_DIRECTOR

Fundação Pio XII - Hospital de Câncer de Barretos

André L Carvalho, PHD

Role: STUDY_DIRECTOR

Fundação Pio XII - Hospital de Câncer de Barretos

Locations

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Barretos Cancer Hospital

Barretos, São Paulo, Brazil

Site Status

Countries

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Brazil

References

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Braathen LR, Szeimies RM, Basset-Seguin N, Bissonnette R, Foley P, Pariser D, Roelandts R, Wennberg AM, Morton CA; International Society for Photodynamic Therapy in Dermatology. Guidelines on the use of photodynamic therapy for nonmelanoma skin cancer: an international consensus. International Society for Photodynamic Therapy in Dermatology, 2005. J Am Acad Dermatol. 2007 Jan;56(1):125-43. doi: 10.1016/j.jaad.2006.06.006.

Reference Type BACKGROUND
PMID: 17190630 (View on PubMed)

De Rosa FS, Bentley MV. Photodynamic therapy of skin cancers: sensitizers, clinical studies and future directives. Pharm Res. 2000 Dec;17(12):1447-55. doi: 10.1023/a:1007612905378.

Reference Type BACKGROUND
PMID: 11303952 (View on PubMed)

Dougherty TJ. A brief history of clinical photodynamic therapy development at Roswell Park Cancer Institute. J Clin Laser Med Surg. 1996 Oct;14(5):219-21. doi: 10.1089/clm.1996.14.219. No abstract available.

Reference Type BACKGROUND
PMID: 9612186 (View on PubMed)

Fink-Puches R, Hofer A, Smolle J, Kerl H, Wolf P. Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light. J Photochem Photobiol B. 1997 Nov;41(1-2):145-51. doi: 10.1016/s1011-1344(97)00096-1.

Reference Type BACKGROUND
PMID: 9440322 (View on PubMed)

Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988 Jun;124(6):869-71. doi: 10.1001/archderm.124.6.869. No abstract available.

Reference Type BACKGROUND
PMID: 3377516 (View on PubMed)

Freeman M, Vinciullo C, Francis D, Spelman L, Nguyen R, Fergin P, Thai KE, Murrell D, Weightman W, Anderson C, Reid C, Watson A, Foley P. A comparison of photodynamic therapy using topical methyl aminolevulinate (Metvix) with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. J Dermatolog Treat. 2003 Jun;14(2):99-106. doi: 10.1080/09546630310012118.

Reference Type BACKGROUND
PMID: 12775317 (View on PubMed)

Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23-4. doi: 10.1067/mjd.2000.103339.

Reference Type BACKGROUND
PMID: 10607353 (View on PubMed)

Jeffes EW, McCullough JL, Weinstein GD, Fergin PE, Nelson JS, Shull TF, Simpson KR, Bukaty LM, Hoffman WL, Fong NL. Photodynamic therapy of actinic keratosis with topical 5-aminolevulinic acid. A pilot dose-ranging study. Arch Dermatol. 1997 Jun;133(6):727-32.

Reference Type BACKGROUND
PMID: 9197826 (View on PubMed)

Kaufmann R, Spelman L, Weightman W, Reifenberger J, Szeimies RM, Verhaeghe E, Kerrouche N, Sorba V, Villemagne H, Rhodes LE. Multicentre intraindividual randomized trial of topical methyl aminolaevulinate-photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the extremities. Br J Dermatol. 2008 May;158(5):994-9. doi: 10.1111/j.1365-2133.2008.08488.x. Epub 2008 Mar 13.

Reference Type BACKGROUND
PMID: 18341663 (View on PubMed)

Kennedy JC, Pottier RH. Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B. 1992 Jul 30;14(4):275-92. doi: 10.1016/1011-1344(92)85108-7.

Reference Type BACKGROUND
PMID: 1403373 (View on PubMed)

Malik Z, Kostenich G, Roitman L, Ehrenberg B, Orenstein A. Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice. J Photochem Photobiol B. 1995 Jun;28(3):213-8. doi: 10.1016/1011-1344(95)07117-k.

Reference Type BACKGROUND
PMID: 7623186 (View on PubMed)

Moloney FJ, Collins P. Randomized, double-blind, prospective study to compare topical 5-aminolaevulinic acid methylester with topical 5-aminolaevulinic acid photodynamic therapy for extensive scalp actinic keratosis. Br J Dermatol. 2007 Jul;157(1):87-91. doi: 10.1111/j.1365-2133.2007.07946.x. Epub 2007 May 14.

Reference Type BACKGROUND
PMID: 17501954 (View on PubMed)

Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):4-7. doi: 10.1067/mjd.2000.103342.

Reference Type BACKGROUND
PMID: 10607349 (View on PubMed)

Sotiriou E, Apalla Z, Maliamani F, Zaparas N, Panagiotidou D, Ioannides D. Intraindividual, right-left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities. J Eur Acad Dermatol Venereol. 2009 Sep;23(9):1061-5. doi: 10.1111/j.1468-3083.2009.03259.x. Epub 2009 Apr 8.

Reference Type BACKGROUND
PMID: 19470041 (View on PubMed)

Szeimies RM, Karrer S, Radakovic-Fijan S, Tanew A, Calzavara-Pinton PG, Zane C, Sidoroff A, Hempel M, Ulrich J, Proebstle T, Meffert H, Mulder M, Salomon D, Dittmar HC, Bauer JW, Kernland K, Braathen L. Photodynamic therapy using topical methyl 5-aminolevulinate compared with cryotherapy for actinic keratosis: A prospective, randomized study. J Am Acad Dermatol. 2002 Aug;47(2):258-62.

Reference Type BACKGROUND
PMID: 12140473 (View on PubMed)

Tschen EH, Wong DS, Pariser DM, Dunlap FE, Houlihan A, Ferdon MB; Phase IV ALA-PDT Actinic Keratosis Study Group. Photodynamic therapy using aminolaevulinic acid for patients with nonhyperkeratotic actinic keratoses of the face and scalp: phase IV multicentre clinical trial with 12-month follow up. Br J Dermatol. 2006 Dec;155(6):1262-9. doi: 10.1111/j.1365-2133.2006.07520.x.

Reference Type BACKGROUND
PMID: 17107399 (View on PubMed)

Yantsos VA, Conrad N, Zabawski E, Cockerell CJ. Incipient intraepidermal cutaneous squamous cell carcinoma: a proposal for reclassifying and grading solar (actinic) keratoses. Semin Cutan Med Surg. 1999 Mar;18(1):3-14. doi: 10.1016/s1085-5629(99)80003-0.

Reference Type BACKGROUND
PMID: 10188837 (View on PubMed)

Other Identifiers

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5-ALAAK

Identifier Type: -

Identifier Source: org_study_id

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