Method of treating bone metastasis

Methods

[0057]ATP was administered to each patient once weekly for eight consecutive weeks as an 8-hour infusion at rates of 50 up to 100 μg / kg / minute; an amount determined to be well tolerated by most patients. In the first week, all patients received ATP infusions starting at 50 μg / kg / minute and was reduced to 25 μg / kg / minute in cases where 50 μg / kg / minute was not well tolerated. If the 50 μg / kg / minute was tolerated, the ATP infusion was increased to 75 μg / kg / minute in the second week. Likewise, if the 75 μg / kg / minute was tolerated, the ATP infusion was increased to 100 μg / kg / minute in the third week. This regime was maintained until the maximally tolerated dose (MTD) was reached. During infusions, all patients were monitored closely for signs and symptoms of adverse effects to ATP. If adverse effects occurred during an ATP infusion, the infusion was terminated immediately. Treatment with Sm-153, pamidronate and TAS occurred 24-hours after the 8 weeks o

Interventions

[0060]ATP infusion therapy was as described above. ATP infusions were administered between 25 and 100 μg / kg / minute for 8 hours for 8 consecutive weeks (Table 4).

[0061]

TABLE 4ATP i.v.Week ofDay ofAdministrationSm-153PamidronateTreatmentWeek(μg / kg / min)(mCi / kg / iv)(mg)1Day 125–50 2Day 150–75 3Day 175–1004Day 175–1005Day 175–1006Day 175–1007Day 175–1008Day 175–1008Day 290,Monthly for12 months9Day 11.0

[0062]Ninety milligrams of pamidronate (AREDIA®, Novartis Corporation, New York, N.Y.) was administered as a two-hour intravenous infusion monthly for 12 cycles starting from week 8, day 2.

[0063]Post-ATP treatment, anti-androgen therapy was administered to patients such that they received total androgen suppression (TAS) using a combination of a goserelin acetate implant (ZOLADEX®, AstraZeneca Pharmaceuticals LP, Wilmington, Del.) and bicalutamide (CASODEX®, AstraZeneca Pharmaceuticals LP, Wilmington, Del.). Bicalutamide, administered orally daily for the duration of go

Measurements

[0065]Blood samples were taken from each patient before, and at intervals during and after infusions on weeks 1, 3, and 8. ATP levels were determined in the plasma and erythrocytes of these samples using standard methodologies and were monitored was used for analysis of treatment regime. Furthermore, ATP blood parameters were measured immediately after Sm-153 treatment.