Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours.

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.

[Experimental study on osteosarcoma of local chemotherapy diffusing from surgical acrylic cement and plaster]. / Etude expérimentale sur l'ostéosarcome d'une chimiothérapie locale diffusant à partir du ciment acrylique chirurgical et du plâtre.

An experimental study has been made to explore the possibility of using plaster or surgical cement as a vehicle for the diffusion of local chemotherapeutic agents in osteosarcoma. In vitro, leeching out of methotrexate from plaster or acrylic cement occurred with a peak during the first few hours followed by a decreasing curve lasting for an average of two weeks. In dogs suffering from a spontaneous osteosarcoma, the loss of substance produced by excision was filled with cement to which methotrexate had been added extemporaneously. This method of administration produced a general diffusion of methotrexate whose blood levels were measured for three to five days. In laboratory rats into which osteosarcomata had been grafted, tablets of plaster containing antimitotic drug were implanted into the tumour, which was left in situ. This made it possible to show that the local chemotherapy was having a true effect, particularly when the antimitotic used was cisplatinum. In patients who had acrylic cement containing methotrexate inserted during operation, local diffusion resulted in very high concentrations, evidenced by the concentration found in fluid obtained from suction drains during the early days after operation.