Two new compounds, 4-[4-[bis-(2-chloroethyl)-amino-]phenyl]-1- hydroxybutane-1,1-bisphosphonic
acid (BAD) and
aminotris-(methylenephosphonato)-diamminoplatinum(II) (
ADP) that both have
cytostatic and osteotropic properties, have shown good therapeutic efficacy against an
osteosarcoma which metastasizes and kills by lung
metastases. We therefore combined each of these drugs with the antimetastic agent
razoxane.
Razoxane (20 mg/kg i.p., 5 days/week for 6 weeks) was administered in combination with either BAD (30 mg/kg i.p.) or
ADP (37.5 mg/kg i.v.) twice weekly for 3 weeks. Tumour volumes,
body weight, survival time and occurrence of
metastases were recorded, in addition to the measurement of the
metastasis area compared to the total lung area in serial histological lung samples. In both experiments,
razoxane effected a significant increase in life span while being ineffective in tumour inhibition.
Razoxane in combination with BAD displayed an enhanced anticancer activity which was not significant.
ADP had a good
antineoplastic activity and a large increase in survival time (144 per cent ILS).
Razoxane used in combination with
ADP did not influence antitumour efficacy. Median survivals of both
ADP-treated groups were significantly longer than the
razoxane-treated group. Analysis of the lung
metastasis area showed a maximum of 57 per cent for the controls while all treated groups occupied a lesser area. The lowest
metastases area was found with the combination treatment BAD + RAZ (18 per cent). This was considered an antimetastatic effect, while
ADP treatment effected a time delay only. No change in metastatic pattern was observed in any of the treatment groups. Histological examination showed no effect on the capillaries in the proliferating region of the tumours that could account for the lower occurrence of
metastases.