A topical solution for superficial basal cell carcinomas

Nonmelanoma skin cancers are the most common malignancies in the global white population, with Basal Cell Carcinomas (BCCs) accounting for up to 80 percent of cases1. However, Aldara cream from Innova Pharma has shown efficacy in treating superficial BCC tumours.

Sun exposure

BCCs are abnormal, uncontrolled growths or lesions that arise in the skin’s basal cells, which line the deepest layer of the epidermis. BCCs often look like open sores, red patches, pink growths, shiny bumps, or scars and are usually caused by a combination of cumulative and intense, occasional sun exposure2.

The incidence of BCC is increasing worldwide by up to 10 percent a year3. More than one out of every three new cancers is a skin cancer, and the vast majority are BCCs2.

While BCC almost never metastasizes beyond the original tumour site, these growths can be disfiguring if not treated promptly.  Only in exceedingly rare cases can it spread to other parts of the body and become life-threatening2. Furthermore, people who have this condition are at high risk of developing further basal cell carcinoma and other malignancies3.

While there are several clinical subtypes of BCC, only two varieties account for the majority of BCC tumours. Nodular BCC’s, which appear mainly on the head and neck, account for up to 80 percent of cases, with superficial BCC (sBCC) accounting for most of the remaining cases of BCC. Most sBCC tumours occur on the trunk and extremities of the body, with several studies showing a steady increase in the incidence of sBCC globally4.

Topical approach

While the treatment aim is to completely cure the tumour, the cosmetic outcome is also of consequence and a concern for most patients5.

When choosing a treatment, healthcare practitioners should ideally take into consideration the long-term clearance rates and patient risk factors for recurrences as well as the cost and number of re-treatments required. And because sBCC generally do not metastasize, the cosmetic outcome is an important factor5.

Aldara-cream

A treatment such as Aldara (imiquimod) five percent cream cream gives healthcare practitioners a non-invasive, patient administered, topical approach4 with proven efficacy6.

Aldara five percent cream has proven to have a well-established safety and efficacy profile for superficial basal cell carcinoma (sBCC) in randomised, double-blind, vehicle-controlled trials7.

In fact, in a non-inferiority randomised controlled trial (RCT), the results of which were cited in the European

Journal of Cancer in June this year, five percent 5-fluorouracil (5-FU) (twice daily for four weeks) was compared with imiquimod five percent cream (once daily, five times a week for six weeks) and methyl aminolevulinate photodynamic therapy (MAL-PDT) (two sessions with an interval of one week) in patients with sBCC followed up for five years8.

The overall estimate of treatment success at one year was 83.4 percent for imiquimod, 80.1 percent for five percent 5-FU and 72.8 percent for MAL-PDT. Five years after treatment, the probability of tumour-free survival was 70.0 percent for five percent 5-FU, 62.7 percent for MAL-PDT and 80.5 percent for imiquimod, the authors have concluded that Aldara (imiquimod five percent) cream is superior to both MAL-PDT and five percent 5-FU in the treatment of patients with primary sBCC8.

 Aldara (imiquimod five percent) has been shown to act as a toll-like receptor-7 agonist, and is thought to exert its anti-tumour effect via modification of the immune response and stimulation of apoptosis in sBCC cells6.

Furthermore, application site reaction was the most common adverse event reported during clinical trials yet were well tolerated as shown by the low percentage of discontinuations due to local skin reactions or application site reactions9. In fact, the severity of erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates6.

Various studies have concluded overall histological clearance rates of up to 85 percent10.

ALDARA (imiquimod five percent) cream is an ideal topical treatment for sBCC that induces a potent immune response, usually resulting in complete histologic clearance of the target tumour10. It is a novel, non-invasive approach to treating sBCC and may have some advantages over surgical procedures, especially when good cosmetic outcome is paramount10.

For the treatment of superficial Basal Cell Carcinoma (sBCC), Aldara cream should be applied once daily for five consecutive days per week and the treatment should continue for six weeks. Sufficient cream should be applied to cover the treatment area, including 1 cm of skin around the tumour. Before applying Aldara cream, the patient should wash the treatment area with mild soap and water, and allow the area to dry thoroughly. Treatment should be applied prior to normal sleeping hours, and should remain on the skin for six to 10 hours11. After this period Aldara cream should be removed with mild soap and water.11

Scheduling status:

S4 Proprietary name and dosage form: ALDARA Cream. Composition: Each 2,0 g cream pump contains 5 % Imiquimod (100 mg). ALDARA Cream Sachet. Composition: Each 250 mg cream sachet contains 5 % Imiquimod (12,5 mg). Preservatives: Methyl hydroxybenzoate 0.2 % m/m, Propyl hydroxybenzoate 0.02 % m/m, Benzyl alcohol 2 % m/m. Pharmacological classification: A 34 Other. Indications: ALDARA Cream is indicated for the topical treatment of superficial basal cell carcinoma (sBCC), and of external genital/perianal warts (condyloma acuminata) and clinically typical, non hyperkeratotic, nonhypertrophic actinic keratosis (AKs) on the face or scalp in adult patients. Registration number: 32/34/0541.

For full prescribing information, refer to the package insert as approved by the SAHPRA (South African Health Products Regulatory Authority). Further information is available on request from iNova Pharmaceuticals. Name and business address: iNova Pharmaceuticals (Pty) Ltd. Co. Reg. No. 1952/001640/07. 15E Riley Road, Bedfordview. Tel. No. 011 087 0000. www.inovapharma.co.za. IN3466/19

References:

1. Quirk C, et al.  Sustained Clearance of Superficial Basal Cell Carcinomas Treated With Imiquimod Cream 5%: Results of a Prospective 5-Year Study. Cutis. 2010;85:318-324.

2. Basal Cell Carcinoma (BCC). Skin Cancer Foundation [Online 2019] [Cited 21 June 2019]. Available from URL: https://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma

3. Wong, CSM. Basal Cell Carcinoma. BMJ 2003;327(7418):794–798.

4. Salasche, S. Imiquimod 5% cream: a new treatment option for basal cell carcinoma. International Journal of Dermatology 2002, 41 (Suppl. 1) 16-20

5. Gollnick H. Recurrence rate of superficial basal cell carcinoma following treatment with imiquimod 5% cream: conclusion of a 5-year long-term follow-up study in Europe. Eur J Dermatol 2008; 18 (6): 677-82.

6. Oldfield V, et al. Imiquimod In Superficial Basal Cell Carcinoma. American Journal of Clinical Dermatology. 2005;6(3):195–200.

7. Vidal D. Topical Imiquimod: Mechanism of Action and Clinical Applications. Min Rev Med Chem. 2006;6:499-503.

8. Peris K, et al. Diagnosis and treatment of basal cell carcinoma: European consensus ebased interdisciplinary guidelines. European Journal of Cancer 2019;118:10 -34.

9. Shumack S, et al. 5% Imiquimod Cream for the Treatment of Large Superficial Basal Cell Carcinoma. Arch Dermatol 2004;140:1286-1287.

10. Geisse J, et al. Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: Results from two phase III, randomized, vehicle-controlled studies. J Am Acad Dermatol 2004;50(5):722-733.

11. Aldara™ approved package insert, August 2007.