The following post is actually a response to a listserve issue over the side effects of Xofigo. I decided to post my response here to avoid the limit of lines allowed on the listserve and because I feel that it is also of interest to my regular readers of this blog.

My response is using the charts (chart 3 and on) found at the following web site . Please go to these charts to follow the discussion.

No question, all treatments come with side effects. Our job is to balance
the side effects against the potential upside of a drug, this is not ever an easy
task.

So, lets look at the side effects of Xofigo based on the clinical trial
experience:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be
directly compared to rates in the clinical trials of another drug and may
not reflect the rates observed in practice.

In the randomized clinical trial in patients with metastatic
castration-resistant prostate cancer with bone metastases, 600 patients
received intravenous injections of 50 kBq/kg (1.35 microcurie/kg) of Xofigo
and best standard of care and 301 patients received placebo and best
standard of care once every 4 weeks for up to 6 injections. Prior to
randomization, 58% and 57% of patients had received docetaxel in the Xofigo
and placebo arms, respectively. The median duration of treatment was 20
weeks (6 cycles) for Xofigo and 18 weeks (5 cycles) for placebo.

The most common adverse reactions (? 10%) in patients receiving Xofigo were
nausea, diarrhea, vomiting, and peripheral edema (Table 3). Grade 3 and 4
adverse events were reported among 57% of Xofigo-treated patients and 63%
of placebo-treated patients. The most common hematologic laboratory
abnormalities in Xofigo-treated patients (? 10%) were anemia,
lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia (Table 4).

Treatment discontinuations due to adverse events occurred in 17% of
patients who received Xofigo and 21% of patients who received placebo. The
most common hematologic laboratory abnormalities leading to discontinuation
for Xofigo were anemia (2%) and thrombocytopenia (2%).

*Adverse Reactions*
Table 3 shows adverse reactions occurring in ? 2% of patients and for which
the incidence for Xofigo exceeds the incidence for placebo.

*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
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 randomized clinical trial, 16% patients in the Xofigo group and 18% patients in the placebo group received cytotoxic chemotherapy after completion of study treatments. Adequate safety monitoring and laboratory testing was not performed to assess how patients treated with Xofigo will tolerate subsequent cytotoxic chemotherapy. Let's try and make heads and tails of this data. The most commonly reported side effects were nausea, diarrhea, vomiting, and peripheral edema. However, the difference between the placebo group and the treatment group was not huge (I do not know if the differences were even statistically significant). Note that for Grade 3 and 4 (the most severe) more adverse events were reported in the placebo group (63%) vs 57% of Xofigo treated men. This is confusing and surprising on the surface. You should note that Xofigo was administered in the trials along with the best standard of care. This means that both men in the treatment arm and men in the placebo arm continued to receive other treatments along with the Xofigo. Xfigo was tested not as an independent drug, but along with the other best standard treatments, whatever they were. So men in both arms received either placebo or Xofigo and their regular treatment. There is no way to parse out what side effects came from the standard of care treatment and what came from the Xofigo. In my opinion it does not look as if the Xofigo added significant side effects, but there is no way to say this for sure. It is hard to think that Xofigo doesn't have side effects, but from looking at the trial they don't seem to be draconian. On the flip side, Xofigo did moderate pain from the mets and it did extend life. Joel T. Nowak, M.A., M.S.W. [/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]