Erythropoietin restores the antitumor effectiveness of photodynamic therapy in mice with chemotherapy-induced anemia

Clin Cancer Res. 2002 May;8(5):1265-70.

Abstract

Purpose: The study was designed to examine the impact of anemia on the antitumor efficacy of photodynamic therapy (PDT) in a murine colon-26 adenocarcinoma model syngeneic with BALB/c mice.

Experimental design: Acute hemolytic anemia was induced by a single i.p. injection of phenylhydrazine hydrochloride (150 mg/kg). Anemia induced by i.p. administration of carboplatin (100 mg/kg) was corrected by s.c. treatment with recombinant human erythropoietin (1000 units/kg/day). The effectiveness of PDT (10 mg/kg Photofrin, 150 J/cm2 laser dose) was evaluated by measurements of the footpad edema and tumor volume. All of the RBC-related parameters were measured from the tail vein.

Results: Phenylhydrazine hydrochloride injection resulted in a blunted response of normal tissues to Photofrin-mediated PDT-induced edema formation. Similarly, the antitumor response in mice with hemolytic anemia was nearly completely abrogated. The antitumor effectiveness of PDT was also significantly diminished in a more realistic clinical situation when anemia was induced by administration of carboplatin. Importantly, administration of recombinant human erythropoietin completely restored the sensitivity of the tumor to PDT in carboplatin-treated mice.

Conclusions: These results indicate that anemia can negatively influence the therapeutic effectiveness of PDT. For optimal antitumor response anemia should be corrected before PDT procedure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Anemia / chemically induced
  • Anemia / complications*
  • Anemia, Hemolytic / chemically induced
  • Anemia, Hemolytic / complications
  • Animals
  • Antineoplastic Agents / administration & dosage
  • Carboplatin / administration & dosage
  • Disease Models, Animal
  • Erythropoietin / pharmacology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Neoplasms, Experimental / complications
  • Neoplasms, Experimental / drug therapy*
  • Phenylhydrazines / administration & dosage
  • Photochemotherapy*
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Phenylhydrazines
  • Recombinant Proteins
  • phenylhydrazine
  • Erythropoietin
  • Carboplatin