Adverse events across generations of bone-modifying agents in patients with solid tumor cancers reported in Phase III randomized trials.
OBJECTIVE
The objective of this study is to compare adverse events experienced among different bone-modifying agents.


METHODS
A literature search was conducted to identify Phase III bisphosphonate and bone-modifying agent trials reporting adverse effects. Thirty-seven adverse events of interest were identified for six different treatment options. Weighted linear regression modeling was performed on the adverse event proportions with treatment groups, normalized through applying natural log transformations.


RESULTS
There were significant differences in adverse events of vomiting (p = 0.045) and osteonecrosis of the jaw (p = 0.017), and combined item events of nausea/vomiting (p = 0.048), hematological and lymphatic system toxicities (p = 0.020), and any respiratory system problem (p = 0.023) between bone-modifying agent and placebo trials. The significant toxicities were observed even after adjusting for the two confounding factors of age and primary cancer site.


CONCLUSIONS
While adverse effects are consistently experienced more frequently in patients receiving bone-modifying agents when compared with placebos, we find that the majority of individual side effects are not significantly more frequent in patients receiving bone-modifying agents compared with placebo.
Odette Cancer Center, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada.
Michael
M
Poon
Liying
L
Zhang
Florence
F
Mok
Kenneth
K
Li
Urban
U
Emmenegger
Erin
E
Wong
Michelle
M
Zhou
Henry
H
Lam
Nicholas
N
Lao
Edward
E
Chow
D000328:Adult; D000367:Age Factors; D000368:Aged; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000145:classification; D001862:Bone Resorption / Q000150:complications / Q000517:prevention & control*; D017326:Clinical Trials, Phase III as Topic; D004164:Diphosphonates / Q000009:adverse effects* / Q000145:classification; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D004164:Diphosphonates