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Treatment of Superficial Basal Cell Carcinoma by Topical Photodynamic Therapy With Fractionated 5-aminolevulinic Acid 20% Versus Two Stage Topical Photodynamic Therapy With Methylaminolevulinate

Phase 4
18 Years
Not Enrolling
Superficial Basal Cell Carcinoma

Thank you

Trial Information

Treatment of Superficial Basal Cell Carcinoma by Topical Photodynamic Therapy With Fractionated 5-aminolevulinic Acid 20% Versus Two Stage Topical Photodynamic Therapy With Methylaminolevulinate

- Basal cell carcinoma throughout the world

Skin cancer is the most common form of cancer, with basal cell carcinoma (BCC) being the
most common form of all skin cancers, and the incidence is still rising.1,2 Of all types of
BCC, superficial basal cell carcinoma (sBCC), is the histopathologic subtype with the
fastest growing incidence, especially on the trunk in younger patients.3-5 It is a common
health problem and although there is no chance of metastasis it can lead to more aggressive
forms of BCC with the ability to cause serious local destruction.

- Treatment options

The DBC (diagnose behandel combinatie) cost price, the amount received for diagnostic and
treatment of one BCC, for surgical excision is partly free negotiable between each hospital
and health insurances. Only the DBC cost price of patients whose health insurance has no
contract with the hospital is public for everyone. This leads to around 18 million euro
(based on a cost price of 400.00 euro for 44,000 new BCCs per year) that is yearly spent on
the surgical treatment of BCC in the Netherlands and cost will only increase in future with
the growing incidence.6 For most BCC subtypes the only effective treatment is surgery but
for sBCC other non-invasive treatments like photodynamic therapy (PDT) are suitable. It is
well accepted in today's dermatologic practice that surgical excision can be considered as
over-treatment for sBCC.7-9 PDT is superior to surgical excision in primary sBCC of any size
in low-risk sites.9 As a consequence unnecessary anaesthesia and incisions are avoided
thereby preventing side-effects, such as scars, haematomas or functional disruption, and
healthy tissue is preserved. MAL is a worldwide registered agent for the use of topical PDT
in sBCC while 5-ALA is not registered in the European Union. In the Netherlands both
fractionated 5-ALA 20% and MAL PDT in 2 sessions are used as treatment for sBCC. Although
there are studies showing the effectiveness of both treatment regimens, the effectiveness,
costs and patient preferences have never been studied in a prospective randomised trial.

- Developments in treatment: photodynamic therapy

PDT has become increasingly implemented in standard care for sBCC in the last years.8-10
Nowadays, in the Maastricht University Medical Centre, about 60% of patients are treated
with PDT. Similar situations are found in the Erasmus MC Rotterdam and the VieCuri Medical
Centre Venlo/Venray. On national level, around two thirds of patients are treated with MAL
PDT in 2 sessions and one third with fractionated 5-ALA 20% PDT. This distribution is
historically determined and not based on evidence based research.

- 5-ALA 20% PDT versus MAL PDT

There are only a few randomised controlled studies on treatment of the most common skin
cancer.11 Choice of PDT treatment with fractionated 5-ALA 20% or MAL in 2 sessions often
depends on the experience and choice of the physician or the availability of the precursor
in a hospital. World-wide, most studies are performed with MAL and it has been accepted as
the standard of care in PDT.12 However, according to the literature, the effectiveness in
terms of clearance rates is in different studies lower for MAL in two sessions compared to
fractionated 5-ALA 20% PDT: 79% versus 97% intention to treat (ITT) after one year in
sBCC.13,14 Contra dictionary, MAL has the theoretical benefit of being more and faster
absorbed in the cell than 5-ALA 20% and, thereby, should generate a higher production of
protoporphyrin IX. In addition MAL has higher selectivity for tumour cells, inducing fewer
side-effects in normal tissue. 15,16 This discrepancy between theoretical working mechanism
and clearance rates needs further clinical research of the effectiveness of both treatments.

PDT is a hospital administered treatment modality during which patients have to come to the
hospital one day (fractionated 5-ALA 20%) or two days one week apart (MAL in 2 sessions).
Patient compliance could be higher with fractionated 5-ALA 20% than with MAL in 2 sessions
because patients have to visit the hospital a second time. At some parts of the body
patients experience a variable burning pain sensation during PDT which might influence
completing the treatment. Kuijpers et al. found no significant differences in pain scores
between ALA-PDT in 2 sessions and MAL PDT in 2 sessions.17 We expect 5-ALA 20% PDT to have
more side-effects in our study as patients are treated twice on the same day.

Furthermore it is important to take into consideration the differences in patient
acceptability costs (see 'economic evaluation').18 A well-designed study comparing the two
topical PDT treatment modalities: fractionated 5-ALA 20% and MAL in 2 sessions will provide
the answers needed to establish the position of the two modalities in the treatment of
patients with sBCC. The conclusions from the proposed study can serve as a basis for
updating guidelines for the treatment of sBCC to catch up with recent developments in
clinical practice.

Inclusion Criteria:

- Minimal age of 18 years

- Histological proven BCC

- Primary BCC (no previous treatment)

- Being able to understand instructions

Exclusion Criteria:

- Age under 18 years

- No histological proven BCC

- Recurrent BCC (previously treated)

- Not able to understand instructions

- Concomitant disease requiring systematic immunosuppressive treatment

- Genetic skin cancer disorders

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Outcome Measure:

Treatment failure

Outcome Description:

Histological proven treatment failure one year after treatment of sBCC with fractionated 5-ALA 20% PDT versus MAL PDT in 2 sessions. If there is any clinical suspicion of residual tumour at control visits 3 and 12 months posttreatment, a 3 mm punch biopsy will be taken to confirm the diagnosis by histopathology.

Outcome Time Frame:

12 months posttreatment

Safety Issue:



Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:




Start Date:

July 2013

Completion Date:

April 2015

Related Keywords:

  • Superficial Basal Cell Carcinoma
  • Superficial basal cell carcinoma
  • Carcinoma, Basal Cell
  • Skin diseases
  • Connective tissue diseases
  • Treatment
  • Drug therapy
  • Efficacy
  • Photodynamic therapy
  • Photosensitizing Agents/therapeutic use
  • Aminolevulinic acid
  • Methylaminolevulinate
  • Pain measurement
  • Health Care Economics and Organizations
  • Carcinoma
  • Carcinoma, Basal Cell