617P Granada Congress and Exhibitions Centre
6th European Congress of Pharmacology (EPHAR 2012)

 

 

Safety and effectiveness of 5-aminolevulinic acid: comparison between clinical trial and preliminary data of a descriptive study

E Montane1,2, P Teixidor3, M Tardaguila3, G Villalba4, MA Arraez5, R Florensa3. 1Hospital Universitari Germans Trias i Pujol, Department of Clinical Pharmacology (Barcelona), Spain,2Universitat Autònoma de Barcelona, Department of Pharmacology, Therapeutics, and Toxicology (Barcelona), Spain, 3Hospital Universitari Germans Trias i Pujol (Barcelona), Department of Neurosurgery (Barcelona), Spain, 4Hospital del Mar, Department of Neurosurgery (Barcelona), Spain, 5Hospital Carlos Haya, Department of Neurosurgery (Málaga), Spain.

 

Background: The 5-aminolevulinic acid (5-ALA) is an orphan drug authorized by the European Medicines Agency (EMA) in 2007 and still with little evidence of efficacy and safety data. There are two randomized clinical trials published comparing 5-ALA to conventional white-light for resection of malignant glioma. A total of less than 350 patients treated with 5-ALA have been included and assessed in clinical trials.1,2

Objective: To compare effectiveness and safety of 5-ALA between the patients included in the pivotal clinical trial1 and the patients included in our prospective ongoing study.

Methods: Demographic, clinical, laboratory, radiological, and safety data from treated with 5-ALA patients included in the pivotal clinical trial were compared to preliminary data of a prospective cohort of patients treated with 5-ALA included in a descriptive study. Survival data are still not assessed. Statistical analyses: Descriptive statistical analyses.

Results: Baseline characteristics, efficacy, and safety data comparison are showed in the table 1.

 

 

 

Pivotal Clinical Trial

 

Prospective Cohort study

Patients treated with 5-ALA

139

42

 

Baseline characteristics

Age
Median (range)
≤55
>55

 

60 (23-73)
45 (32%)
94 (68%)

 

57 (23-79)
17 (40.5%)
25 (59.5%)

Karnofsky scale basal
≤80
>80

 

28 (20%)
111 (80%)
Range (70-100%)

 

10 (25%)
30 (75%)
Range (30-100%)

Tumour location
Non-eloquent
Eloquent

 

65 (47%)
74 (53%)

 

24 (58.5%)
17 (41.5%)

Pathological analysis
Grade III
Grade IV

 

4 (3%)
135 (97%)

 

7 (18.4%)
31 (81.6%)

 

 

Efficacy

 

Exclusions (histological criteria)

N=161 (randomised)

16 (9.9%)

N=42

4 (9.5%)

Complete Tumour resection 

90 (65%)

17 (47%)

 

 

Safety

Hepatobiliar (24h after surgery)
median (range)
GGT
AST
ALT

Times upper limit of normal

0.93 (0.18-9.71)
0.72 (0.22-5.60)
1.05 (0.32-8.53)

Times upper limit of normal

1.45 (0.45-5.35)
0.52 (0.25-1.68)
0.90 (0.23-8.05)

Hematologic

Not available

Leukocytosis, anaemia and/or thrombocytopenia (75%)

Neurologic (early)
Hemiparesis
Convulsions
Epidural hematoma

 

4 (3%)
3 (2%)
1 (1%)

 

2 (5%)
3 (8%)
3 (8%)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Conclusions: Patient’s characteristics, as well as efficacy and safety results of clinical trials, usually differ from clinical practice. Patients included in the clinical trial had less frequency of grade III glioma (3% vs 18.4%) and reached more complete resection of the tumour (65% vs 47%). They also had fewer neurologic surgical complications (hemiparesia, convulsions and epidural hematoma) (1-3% vs 5-8%), but transaminases were higher at 24h after surgery. These differences in the tumour characteristics, efficacy and safety need further and detailed analysis.

 

1. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reuien HJ (2006). Fluorescence-guide surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7: 392-401.
2. Stummer W, Tonn JC, Mehdorn HM, Nestler U, Franz K, Goetz C, et al. (2011). Counterbalancing risks and gains from extended resections in malignant glioma surgery: a supplemental analysis from the randomized 5-aminolevulinic acid glioma resection study. J Neurosurg 114(3): 613-623.