Potentiation of the 5-aminolevulinic acid-based photodynamic therapy with cyclophosphamide

We have investigated the efficacy of the Photodynamic Therapy (PDT) from 5-aminolevulinic acid (ALA) in combination with an antineoplastic agent using an in vitro-in vivo model developed in our laboratory. The alkylant cyclophosphamide (CY) was chosen because there is evidence of the porphyrinogenic properties of this drug. Male BALB/c mice bearing a transplantable mammary adenoarcinoma were given two doses of 35 mg de CY/kg wt. i.p. and 9 mg/kg wt intratumorally. At 16, 22 and 40 hrs after the last injection of CY the animals were sacrificed and explants of 2 mg of tumor were incubated 2 hrs in a medium containing 0.6 mM ALA; and then irradiated with a He-Ne laser. Innocula of 1 mm3 of irradiated and non-irradiated tissue were then injected subcutaneously under the right and left flanks of a normal mouse, respectively. The efficacy of the treatment was determined following the growth of the tumor from day 10 after tumor implantation. Under the present conditions a 30% increased efficacy was observed in the case of the explants treated with CY 40 hrs after the last i.p. injection. Porphyrins in the liver and tumor and other tissues of the injected mice were also determined; except for a slight increase in tumor and liver, 40 and 22 hrs after CY i.p. injection respectively, no other changes were observed in any tissue, as compared with not CY treated mice. These results indicate that future treatment, combining the tumor localizing properties of endogenously formed porphyrins from ALA and antineoplasic drugs such as cyclophosphamide, should be encouraged.