Enhancement of methyl-aminolevulinate photodynamic therapy by iron chelation with CP94: an in vitro investigation and clinical dose-escalating safety study for the treatment of nodular basal cell carcinoma.
OBJECTIVE
Methyl-aminolevulinate (MAL) photodynamic therapy (PDT) is a cancer therapy that combines the selective accumulation of a photosensitizer in tumor tissue with visible light (and tissue oxygen) to produce reactive oxygen species. This results in cellular damage and ablation of tumor tissue. Combining iron chelators with MAL has the potential to increase the accumulation of the photosensitizer protoporphyrin IX (PpIX) by reducing its bioconversion to heme. This paper investigates this method of enhancement both in vitro and for the first time clinically for the treatment of nodular basal cell carcinoma (BCC).


METHODS
Enhancement of MAL-induced PpIX accumulation by the iron chelator CP94 was quantified fluorometrically in human cultured cells (including three dermatological cell types). An open, dose-escalating, pilot study was then conducted in patients with nodular BCC, to determine the safety of this pharmacological modification.


RESULTS
Large enhancements in PpIX accumulation were observed in the cultured cells when co-incubated with the iron chelator CP94. Clinically the addition of CP94 was found to be feasible and safe. In addition greater reductions in tumor depth were observed in the CP94 co-incubated tumors.


CONCLUSIONS
Iron chelation by CP94 is an effective enhancer of MAL-induced PpIX accumulation in vitro. This method of enhancement was safely applied to a clinical PDT protocol with no unexpected adverse effects reported. Although the clinical investigation was only intended to be a small pilot to assess safety, enhancements in tumor clearance were observed both clinically and histologically when CP94 was included in the photosensitizing cream.
Pye
Andrew
A
Cornwall Dermatology Research, Peninsula Medical School, Knowledge Spa, Royal Cornwall Hospital, Treliske, Truro, Cornwall, TR1 3HD, UK. andrew.pye@pms.ac.uk
Campbell
Sandra
S
Curnow
Alison
A
D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D002280:Basal Cell Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D006801:Humans; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D010865:Pilot Projects; D011524:Protoporphyrins / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000188:drug therapy*
D007502:Iron Chelating Agents; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D011728:Pyridones; C068543:1,2-diethyl-3-hydroxypyridin-4-one; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX