pper Limit of Normal); Grade4 (greater than 6x Upper Limit of Normal)
* Serum creatinine data for all patients randomized after the 15-minute infusion amendment
2 Grade3 (less than 7mg/dL); Grade4 (less than 6mg/dL)
3 Grade3 (less than 2mg/dL); Grade4 (less than 1mg/dL)
4 Grade3 (greater than 3mEq/L); Grade4 (greater than 8mEq/L)
5 Grade3 (less than 0.9mEq/L); Grade4 (less than 0.7mEq/L)
Table 9: Grade 4 Laboratory Abnormalities for Serum Creatinine, Serum Calcium, Serum Phosphorus, and Serum Magnesium in Three Clinical Trials in Patients with Bone Metastases Grade 4
Laboratory Parameter Zometa Pamidronate Placebo
4mg 90mg
n/N (%) n/N (%) n/N (%)
Serum Creatinine1* 2/529 (<1%) 1/268 (<1%) 0/241 —
Hypocalcemia2 7/973 (<1%) 3/536 (<1%) 2/415 (<1%)
Hypophosphatemia3 5/973 (<1%) 0/537 — 1/415 (<1%)
Hypermagnesemia4 0/971 — 0/535 — 2/415 (<1%)
Hypomagnesemia5 2/971 (<1%) 1/535 (<1%) 0/415 —
1 Grade3 (greater than 3x Upper Limit of Normal); Grade4 (greater than 6x Upper Limit of Normal)
* Serum creatinine data for all patients randomized after the 15-minute infusion amendment
2 Grade3 (less than 7mg/dL); Grade4 (less than 6mg/dL)
3 Grade3 (less than 2mg/dL); Grade4 (less than 1mg/dL)
4 Grade3 (greater than 3mEq/L); Grade4 (greater than 8mEq/L)
5 Grade3 (less than 0.9mEq/L); Grade4 (less than 0.7mEq/L)
Among the less frequently occurring adverse events (less than 15% of patients), rigors, hypokalemia, influenza-like illness, and hypocalcemia showed a trend for more events with bisphosphonate administration (Zometa 4mg and pamidronate groups) compared to the placebo group.
Less common adverse events reported more often with Zometa 4mg than pamidronate included decreased weight, which was reported in 16% of patients in the Zometa 4mg group compared with 9% in the pamidronate group. Decreased appetite was reported in slightly more patients in the Zometa 4mg group (13%) compared with the pamidronate (9%) and placebo (10%) groups, but the clinical significance of these small differences is not clear.
Renal Toxicity
In the bone metastases trials, renal deterioration was defined as an increase of 0.5mg/dL for patients with normal baseline creatinine (less than 1.4mg/dL) or an increase of 1.0mg/dL for patients with an abnormal baseline creatinine (greater than or equal to1.4mg/dL). The following are data on the incidence of renal deterioration in patients receiving Zometa 4mg over 15minutes in these trials (seeTable10).
Table 10: Percentage of Patients with Treatment Emergent Renal Function Deterioration by Baseline Serum Creatinine* Patient Population/Baseline Creatinine
Multiple Myeloma and Breast Cancer Zometa 4mg Pamidronate 90mg
n/N (%) n/N (%)
Normal 27/246 (11%) 23/246 (9%)
Abnormal 2/26 (8%) 2/22 (9%)
Total 29/272 (11%) 25/268 (9%)
Solid Tumors Zometa 4mg Placebo
n/N (%) n/N (%)
Normal 17/154 (11%) 10/143 (7%)
Abnormal 1/11 (9%) 1/20 (5%)
Total 18/165 (11%) 11/163 (7%)
Prostate Cancer Zometa 4mg Placebo
n/N (%) n/N (%)
Normal 12/82 (15%) 8/68 (12%)
Abnormal 4/10 (40%) 2/10 (20%)
Total 16/92 (17%) 10/78 (13%)
*Table includes only patients who were randomized to the trial after a protocol amendment that lengthened the infusion duration of Zometa to 15minutes.
The risk of deterioration in renal function ap
