Impact of Zoledronic Acid on Renal Function in Patients With Cancer ...

McDermott, Kloth, Wang, et al
Table 4
Univariate Analysis for Predictors <strong>of</strong> Deterioration in Renal Function
FACTOR VARIABLE PATIENTS (n) EVENTS (n) P VALUE a ODDS RATIO [95% CI]
Gender Male 222 22 0.7229 1.12 [0.59, 2.12]
Female 224 20
Age a 446 42 0.0160 1.04 [1.01, 1.07]
Baseline creatinine level < 1.4 mg/dL 407 34 0.0167 0.35 [0.15, 0.83]
≥ 1.4 mg/dL 39 8
Doses a 446 42 0.0455 1.05 [1.00, 1.09]
Diabetes No 388 33 0.0933 0.51 [0.23, 1.12]
Yes 58 9
Hypertension No 277 19 0.020 0.47 [0.25, 0.89]
Yes 169 23
NSAID, current use No 338 24 0.0040 0.38 [0.20, 0.74]
Yes 108 18
Diuretic, current use No 369 30 0.0454 0.48 [0.23, 0.98]
Yes 77 12
Aspirin, current use No 386 36 0.8680 0.93 [0.37, 2.30]
Yes 60 6
Cisplatin, current or prior use No 431 39 0.1670 0.40 [0.11, 1.47]
Yes 15 3
Thalidomide, current or prior use No 433 38 0.0142 0.22 [0.06, 0.74]
Yes 13 4
Cancer diagnosis Myeloma 35 5 0.0276 1.88 [0.68, 5.17]
(myeloma vs other)
Renal 19 5 4.02 [1.36, 11.87]
(renal vs other)
Other 392 32 0.47 [0.12, 1.88]
(myeloma vs renal)
Bold numbers represent statistical significance.
a
Treated as a continuous variable. Abbreviations: CI = confidence interval; NSAID = nonsteroidal anti-inflammatory drug
doses received, a diagnosis <strong>of</strong> renal cell carcinoma or myeloma,
hypertension, concomitant therapy with NSAIDs or diuretics,
and current or prior therapy with thalidomide.
MULTIVARIATE ANALYSIS
Stepwise variable selection in the context <strong>of</strong> binary logistic
regression identified the following subset <strong>of</strong> factors significantly
and independently associated with renal deterioration: patient
age, a diagnosis <strong>of</strong> myeloma or renal cell cancer, the number
<strong>of</strong> doses received, concomitant therapy with an NSAID, and
current or prior therapy with cisplatin (Table 5).
PREDICTIVE MODEL
The subset <strong>of</strong> factors found to be significant on multivariable
analysis was used to construct a logistic regression model
to predict patient risk <strong>of</strong> developing renal deterioration while
on therapy with zoledronic acid. According to this model, a
patient is classified as having experienced renal deterioration
only if his or her predicted risk (ie, estimated conditional
probability) is greater than a selected threshold. In particular,
if the threshold is set at 10%, as is consistent with the available
literature on the incidence <strong>of</strong> renal deterioration with the
use <strong>of</strong> zoledronic acid, the logistic regression prediction model
to identify patients with renal deterioration was observed to
have a sensitivity <strong>of</strong> 64.3% and a specificity <strong>of</strong> 69.8%. Figure
1 shows the ROC curve associated with the multivariable logistic
regression model. The area under the ROC curve was
estimated to be 0.75.
CLINICAL SIGNIFICANCE
The patient care pathway subsequent to the development <strong>of</strong>
renal deterioration is outlined in Figure 2. In 19 cases, zoledronic
acid therapy was continued. Two <strong>of</strong> these patients had developed
obstructive uropathy due to progressive disease in the pelvis
(one with prostate cancer, one with renal cancer). Following
urologic intervention, serum creatinine levels normalized, and
zoledronic acid therapy was resumed. In 17 cases, zoledronic
acid was continued as the treating physician thought that the
rise in serum creatinine levels was not clinically significant. In
nine <strong>of</strong> these cases, serum creatinine levels subsequently fell
with continued therapy so they no longer fulfilled the definition
<strong>of</strong> renal deterioration. In seven cases, serum creatinine levels
remained stable with continued therapy, fulfilling the criteria
for renal deterioration, and in one case, although further zoledronic
acid was planned, it had not yet been administered by
study end.
In 23 cases, no further zoledronic acid therapy was administered
after the observation <strong>of</strong> renal deterioration. Of this total,
VOLUME 4, NUMBER 10 ■ NOVEMBER/DECEMBER 2006
www.SupportiveOncology.net
527