Abstract
OBJECTIVE: Photodynamic therapy (PDT) is a promising new treatment modality for head and neck cancer that is based on the uptake of a systemically administered photosensitizer in tumor tissue and local illumination 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)3N(CH3)2, abbreviated as SiPc IV], which yields superior PDT responses in vitro and in vivo compared with other clinically used photosensitizers. However, tumor regrowth following SiPc IV—based PDT is still a therapeutic problem. The benzamide derivatives, for example, have been shown to enhance tumor ablation when used during radiotherapy and chemotherapy. Therefore, we used metoclopramide hydrochloride, a benzamide derivative, to evaluate its effects on PDT response. DESIGN: Intradermally injected human squamous cell carcinoma cells were grown to 40 to 80 mm3 in athymic nude mice and irradiated with 675-nm light (75 J/cm2, 75 mW/cm2) 24 hours after the intraperitoneal injection of SiPc IV (1.0 mg/kg). Metoclopramide hydrochloride (2 to 48 mg/kg) was injected intraperitoneally 1 hour before and 24 and 48 hours after irradiation. RESULTS: Tumors exposed to PDT alone showed 80% to 90% tumor regression with regrowth in most animals within 20 days. Tumors treated with metoclopramide hydrochloride (48 mg/kg) plus PDT demonstrated 100% tumor regression without regrowth up to the time of killing (150 days). No observable toxic effects were clinically apparent with the high doses of metoclopramide. CONCLUSIONS: Our results show that administering metoclopramide in combination with PDT may be a promising approach to the management of head and neck cancer.(Arch Otolaryngol Head Neck Surg. 1995;121:783-789)