Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours

J Bone Joint Surg Br. 1989 Nov;71(5):804-11. doi: 10.1302/0301-620X.71B5.2584251.

Abstract

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Cements / therapeutic use*
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / mortality
  • Diffusion
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Implants
  • In Vitro Techniques
  • Methotrexate / administration & dosage*
  • Methotrexate / pharmacokinetics
  • Methotrexate / toxicity
  • Methylmethacrylates / therapeutic use
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / metabolism
  • Osteosarcoma / mortality
  • Rats
  • Time Factors

Substances

  • Bone Cements
  • Drug Implants
  • Methylmethacrylates
  • Methotrexate