)
Grades 1-4
%
Grades 3-4
%
Grades 1-4
%
Grades 3-4
%
Blood and lymphatic system disorders
Pancytopenia
2
1
0
0
Gastrointestinal disorders
Nausea
36
2
35
2
Diarrhea
25
2
15
2
Vomiting
19
2
14
2
General disorders and administration site conditions
Peripheral edema
13
2
10
1
Renal and urinary disorders
Renal failure and impairment
3
1
1
1
Laboratory Abnormalities
Table 4 shows hematologic laboratory abnormalities occurring in > 10% of patients and for which the incidence for Xofigo exceeds the incidence for placebo.
Table 4: Hematologic Laboratory Abnormalities
Hematologic Laboratory Abnormalities
Xofigo (n=600)
Placebo (n=301)
Grades 1-4
%
Grades 3-4
%
Grades 1-4
%
Grades 3-4
%
Anemia
93
6
88
6
Lymphocytopenia
72
20
53
7
Leukopenia
35
3
10
<1
Thrombocytopenia
31
3
22
<1
Neutropenia
18
2
5
<1
Laboratory values were obtained at baseline and prior to each 4-week cycle.
As an adverse reaction, grade 3-4 thrombocytopenia was reported in 6% of patients on Xofigo and in 2% of patients on placebo. Among patients who received Xofigo, the laboratory abnormality grade 3-4 thrombocytopenia occurred in 1% of docetaxel naïve patients and in 4% of patients who had received prior docetaxel. Grade 3-4 neutropenia occurred in 1% of docetaxel naïve patients and in 3% of patients who have received prior docetaxel.
Fluid Status
Dehydration occurred in 3% of patients on Xofigo and 1% of patients on placebo. Xofigo increases adverse reactions such as diarrhea, nausea, and vomiting which may result in dehydration. Monitor patients’ oral intake and fluid status carefully and promptly treat patients who display signs or symptoms of dehydration or hypovolemia.
Injection Site Reactions
Erythema, pain, and edema at the injection site were reported in 1% of patients on Xofigo.
Secondary Malignant Neoplasms
Xofigo contributes to a patient’s overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure may be associated with an increased risk of cancer and hereditary defects. Due to its mechanism of action and neoplastic changes, including osteosarcomas, in rats following administration of radium-223 dichloride, Xofigo may increase the risk of osteosarcoma or other secondary malignant neoplasms [see Nonclinical Toxicology (13.1)]. However, the overall incidence of new malignancies in the randomized trial was lower on the Xofigo arm compared to placebo (<1% vs. 2%; respectively), but the expected latency period for the development of secondary malignancies exceeds the duration of follow up for patients on the trial.
Subsequent Treatment with Cytotoxic Chemotherapy
In the r
