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

Actinic Keratosis Clinical Trial

Official title:

Evaluation of the Formulation of 5-aminolevulinic Acid With Dimethylsulfoxide in Photodynamic Therapy for Treatment of Actinic Keratosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01459393
• Other study ID #: 5-ALAAK
• Status: Completed
• Phase: Phase 3
• First received: October 12, 2011
• Last updated: June 27, 2017
• Start date: November 2010
• Est. completion date: November 2011

Study information

• Verified date: February 2014
• Source: Barretos Cancer Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Actinic Keratosis
• Keratosis
• Keratosis, Actinic

Intervention

Drug:
• 5-ALA Photodynamic Therapy

• 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.

Locations

Country	Name	City	State
Brazil	Barretos Cancer Hospital	Barretos	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Barretos Cancer Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (17)

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. — View Citation

De Rosa FS, Bentley MV. Photodynamic therapy of skin cancers: sensitizers, clinical studies and future directives. Pharm Res. 2000 Dec;17(12):1447-55. Review. — View Citation

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. — View Citation

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. — View Citation

Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988 Jun;124(6):869-71. — View Citation

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. — View Citation

Glogau RG. The risk of progression to invasive disease. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):23-4. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. Epub 2007 May 14. — View Citation

Salasche SJ. Epidemiology of actinic keratoses and squamous cell carcinoma. J Am Acad Dermatol. 2000 Jan;42(1 Pt 2):4-7. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response rates	Clinical evaluation of treated area.	0 months (baseline), 3 months and 6 months
Secondary	Visual Analogic Scale Pain Score	Pain was evaluated with a Visual Analogic Scale (blind) and a graduated scale. It was evaluated at the time 0 and 15 minutes after each intervention (Cryotherapy or PDT): at the first intervention (0 months), and at the second intervention if the residual lesion that indicates a second session (3 months).; And at the third interwiew (6 months) there was no intervention, but the patients who was submitted to 2 interventions were requested about what intervention was more painfull (the first or the second one).	0 months (baseline), 3 months, 6 months
Secondary	Cosmesis analysis	Cosmesis was evaluated subjetively by the patient as one of the possibilities: aesthetic outcome awfull, bad, regular, good, excellent.; Cosmesis was evaluated subjetively also by the researcher as one of the possibilities: aesthetic outcome awfull, bad, regular, good, excellent.; And there was and objective evaluation of cosmesis by the researcher, the presece or absence of one or more of these criteria: hypochromia, hyperpigmentation,hyperemia, scar.	3 months, 6 months