METOCLOPRAMIDE ENHANCES THE EFFECT OF PHOTODYNAMIC THERAPY ON XENOGRAFTED HUMAN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK

Objective: Photodynamic therapy (PDT) is a promising new treatment mod ality for head and neck cancer that is based on the uptake of a system ically administered photosensitizer in tumor tissue and local illumina tion of the lesion by a high-intensity visible light source, typically a tunable argon-pumped dye laser. We developed a new photosensitizer named silicon phthalocyanine [SiPc(OH) OSi(CH3)(2)(CH2)(3)N(CH3)(2), a bbreviated as SiPc IV], which yields superior PDT responses in vitro a nd in vivo compared with other clinically used photosensitizers. Howev er, tumor regrowth following SiPc IV-based PDT is still a therapeutic problem. The benzamide derivatives, for example, have been shown to en hance tumor ablation when used during radiotherapy and chemotherapy. T herefore, we used metoclopramide hydrochloride, a benzamide derivative , to evaluate its effects on PDT response. Design: Intradermally injec ted human squamous cell carcinoma cells were grown to 40 to 80 mm(3) i n athymic nude mice and irradiated with 675-nm light (75 J/cm(2), 75 m W/cm(2)) 24 hours after the intraperitoneal injection of SiPc IV (1.0 mg/kg). Metoclopramide hydrochloride (2 to 48 mg/kg) was injected intr aperitoneally 1 hour before and 24 and 48 hours after irradiation. Res ults: Tumors exposed to PDT alone showed 80% to 90% tumor regression w ith regrowth in most animals within 20 days. Tumors treated with metoc lopramide hydrochloride (48 mg/kg) plus PDT demonstrated 100% tumor re gression without regrowth up to the time of killing (150 days). No obs ervable toxic effects were clinically apparent with the high doses of metoclopramide. Conclusions: Our results show that administering metoc lopramide in combination with PDT may be a promising approach to the m anagement of head and neck cancer.