Metoclopramide enhances the effect of photodynamic therapy on xenografted human squamous cell carcinoma of the head and neck.

Abstract

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. 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. 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. Our results show that administering metoclopramide in combination with PDT may be a promising approach to the management of head and neck cancer.