Pharmacological modulation of photodynamic therapy with hematoporphyrin derivative and light

The interactions between photodynamic therapy (PDT) with hemotoporphyrin derivative (HPD) and treatment with cytotoxic drugs have been examined using both an in vitro tissue culture assay and an in vivo transplantable mouse tumor assay. Adriamycin (0.5-4.0 mg/kg) administered with HPD and at the time of irradiation potentiated the photodynamic effect, doubling the duration of tumor control. Adriamycin administered after PDT was not as effective. Methotrexate (0.2 mg/kg) also potentiated the tumor response to PDT. The other cytotoxic agents tested, cyclophosphamide, thiotepa, vincristine, and 5-fluorouracil, did not result in significant increases in tumor responses at the doses tested. In contrast to the effects observed in vivo, Adriamycin inhibited the photodynamic destruction of Raji or Lewis lung carcinoma cells in vitro, in part by reducing the uptake of HPD. Methotrexate had no effect on either the uptake of HPD or the efficacy of photodynamic destruction of Raji cells in vitro. The discrepancy between the in vitro and in vivo results implies that the interaction between PDT and other pharmacological agents cannot be assessed in vitro.