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
So, lets look at the side effects of Xofigo based on the clinical trial
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%).
Table 3 shows adverse reactions occurring in ? 2% of patients and for which
the incidence for Xofigo exceeds the incidence for placebo.
Table 4 shows hematologic laboratory abnormalities occurring in > 10% of
patients and for which the incidence for Xofigo exceeds the incidence for
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
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
)]. 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]
I have MCRPC. Finished 10 days of palliative radiation to my T8-T10 vertebra and 10th rib 10/1/13. Contemplating starting Xofigo treatments soon. Thank you for this very informative series of articles. They are the most comprehensive, informative and objective I have run across. Answers so very many of my questions.
My father (78) just finished his fourth Xofigo treatment and is doing great! He is experiencing no side effects at this time. It has reduced his pain and improved his mobility. He also has a great appetite and regained a little weight lost during his one round of chemo. If we had to do it over we would consider not doing chemo as it was very hard on his body and really set him back health wise. Not sure if can go straight to Xofigo without having chemo but for older patients I hope doctors evaluate that approach. My dad has lived an active life for the past 20 years since diagnosed and we are blessed to still have him in our lives! Positive thoughts go out to all families dealing with PC.
I cannot report a good outcome from the use of Xofigo. My husband had a single injection of Xofigo on August 1, 2013. He immediately experienced stabbing pain in his low back and began an intractable cycle of nausea, vomiting, and anorexia which resulted in weight loss of 30 lbs in 19 days, resulting in severe dehydration, hypercalcemia and complete loss of muscle strength and control. He died at the end of Thanksgiving weekend. An autopsy completed by the hospital reported acute GI bleeding (he also had spontaneous nose bleeds), pulmonary infection and calcified basement membranes in his kidneys.
I am truly sorry for your loss. I do hope that you and your family find a way to heal as quickly as possible. – Joel
My husband has MCRPC that has spread to the bones. Has in lower an upper back,femur an ribs. Had radiation last fall (lower back) did help with pain. Pain in ribs now an had new bone scan which showed other areas. Dr has suggested this treatment with Xofigo an feel this is a good option for him because of the new areas on bone scan. My husband is having a difficult time deciding on this treatment because of side affects. He realizes most of the time the side affects don’t occur but in his case( had vomiting an nausea) with radiation to back last fall an also has heart issues,pacemaker with defibrillator an myasthenia gravis which at times really complicates the treatments. I’m trying to read all about this radiation treatment in hopes of making the decision that will be right for him at this stage of his cancer.. I’m so glad for all the information that I’ve found. God bless all who are dealing with cancer.
I hope that you and your husband find a way to spend many more years together in happiness and HEALTH – Joel
I have MCRPC that was diagnosed almost 2 years ago. Unfortunately, by the time I was diagnosed with prostate cancer, it had already spread to my spine, ribs, left femur head and a few spots in my shoulder. I have been on ADT with Lupron and Xgeva first then added casodex as PSA bottomed out then started to rise again. I tried 2 months of THCA treatment with no success. I have been off the Lupron and Xgeva for around 6 months due to cost and bone pain caused by the Xgeva. I had External Beam radiation of my upper back due to pain. This caused permanent damage to my esophagus (difficulty swallowing, etc) so I will not be doing that again. Since stopping the Xgeva and lupron, the bone pain has almost disappeared. Last bone scan shows complete spinal involvement. I am going to see my oncologist in 2 days and am heavily considering radium 223.
I realise your post was a few years ago but in September, 2020, my husband had two months of treatment with Xofigo. Before this treatment he was able to go shopping and live a normal life even though his prostate cancer, unfortunately an aggressive type, was getting worse. Although he didn’t have too much pain he was able to cope, anyway his Onc., suggested he try this Xofigo and he managed two injections before he became too ill to continue. He then had radiation treatment, one time only, on his chest area which damaged his esophagus. He had been on Xgeva for two years and had stopped just before his second six months of Docetaxil, so he was about seven months stopped the Xgeva before the Xofigo treatments. He just got steadily worse and ended up being bedridden. I believe, because of the Xofigo hardening his bones, the Xofigo bounced off his bones and spread the cancer all over his body. I did look at some reviews but didn’t look at the interactions, otherwise i’d have seen that Xgeva is one of them. My husband, very sadly, passed away less than three months after taking this Xofigo. I would research it thoroughly before trying it and I hope that, if you did go on it, you will have much better results than my husband had with it. I’m very surprised that his Oncologist did not know this information regarding other drug interactions. With all good wishes for your continued success against this horrible cancer. Regards, Joan Wilson