Enhancement of interstitial photodynamic therapy by mitomycin C and EO9 in a mouse tumour model.
The tumoricidal effect of interstitial photodynamic therapy (IPDT) using Photofrin was found to increase when combined with the bioreductive alkylating agent mitomycin C (MMC) and, to a lesser extent, with the indoloquinone EO9. When MMC was given prior to IPDT or RIF1 tumours, the light dose required for a given regrowth time or for 50% cure was reduced by a factor of 2 compared with IPDT alone. MMC given immediately after illumination did not increase the effects of IPDT, although MMC plus illumination without photosensitizer produced a significant increase in regrowth time compared with MMC or light alone. Combination of IPDT with EO9, given directly before illumination, only marginally increased the tumour regrowth times at non-toxic doses. These results demonstrate that combining IPDT with MMC greatly improves the tumour response. Factors such as PDT-induced hypoxia, pH changes, temperature increases and production of toxic reactive oxygen species by both drugs may play a role in the enhanced MMC cytotoxicity.
Baas
P
P
Division of Experimental Therapy (H6), The Netherlands Cancer Institute, Amsterdam.
Michielsen
C
C
Oppelaar
H
H
van Zandwijk
N
N
Stewart
F A
FA
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001388:Aziridines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004354:Drug Screening Assays, Antitumor; D005260:Female; D045563:Indolequinones; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D016685:Mitomycin / Q000627:therapeutic use*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*
D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; D007211:Indoles; D016685:Mitomycin; C060817:apaziquone