Samarium-153-labelled EDTMP for bone metastases from cancer of the prostate

A Phase I dose-escalation trial of a bone seeking phosphonate labelled with Samarium-153 was conducted on heavily pretreated patients with widespread bony metastases from cancer of the prostate. The bone marrow dose was calculated initially on a 4:1 uptake of cortical to cancellous bone, but subsequent information suggested the distribution was approximately equal so that the marrow received about three times the dose that has been prescribed. As a result, what were at first thought to be doses of 0.5 Gy, 1.0 Gy and 1.5 Gy were probably 1.5 Gy, 3.0 Gy and 4.5 Gy respectively. Three patients were treated at each dose level. The dose was repeated in the first three. Pain relief was delayed for 2 weeks, and was maximal by 4 weeks. All but one patient gained some benefit but this was transitory, lasting only 4-6 weeks in most. A recalculated dose of 3 Gy proved the most effective. The major toxicity was to platelets. Thrombocytopenia was fatal in four cases (two with repeat doses). All patients died but three survived more than 6 months with the help of third line hormonal measures and local radiotherapy to maintain comfort. A second group of five patients, not previously irradiated, were given 153Sm-EDTMP to a marrow dose of 3 Gy and all have survived for more than 4 months and achieved minimal to excellent relief of pain. The technique is recommended as initial therapy in unirradiated patients with good bone marrow function and with significant pain above and below the diaphragm, making half-body irradiation less likely to be a useful palliative procedure.