Effects of chlorin-mediated photodynamic therapy combined with fluoropyrimidines in vitro and in a patient.
Although photodynamic therapy (PDT) is becoming an additional cancer therapy, only little is known about its interactions with other drugs and treatment modalities in vitro and in vivo. We investigated the combination of 5-fluoro-2'-deoxyuridine (5FdUr), a chemotherapeutic drug, with 5,10,15,20-tetra( m-hydroxyphenyl)chlorin (mTHPC), a potent photosensitizer. Two cell lines, MCF-7 and LNCaP, were either simultaneously or consecutively incubated with both drugs and irradiated with laser light to activate mTHPC, and cell survival was determined. The combination of the two treatments was additive or antagonistic in LNCaP cells but additive or synergistic in MCF-7 cells depending on the protocol and concentration of 5FdUr. In one patient with multiple basal cell carcinoma, the effect of the combination of 5-fluorouracil administration followed by PDT resulted in significantly stronger effects than expected, leading to severe oedema, redness and ulceration. The healing process was delayed by 2 months compared to PDT alone. It is therefore important to find optimal conditions under which PDT and chemotherapy combinations do not fall outside the therapeutic window.
Zimmermann
Andrea
A
Research Division of Gynaecology, Department of Gynaecology and Obstetrics, University Hospital Zurich, 8091 Zurich, Switzerland.
Walt
Heinrich
H
Haller
Urs
U
Baas
Paul
P
Klein
Sabine D
SD
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002280:Basal Cell Carcinoma / Q000188:drug therapy*; D005467:Floxuridine / Q000627:therapeutic use*; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy; D012878:Skin Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011166:Porphyrins; D005467:Floxuridine; C006969:chlorin; C072269:temoporfin; D005472:Fluorouracil