What Injectible Bone Agent Lessens the Risk of NEW Bone Metastasis?

[Shorehousejam]

Thank you

[Tall_Allen]

Two major RCTs proved they don't.

[Shorehousejam in reply to Tall_Allen]

I just wanted to be assured I read that correctly, thank you

[Schwah in reply to Tall_Allen]

I thought a phase three study showed the combination of Zometa and Celebrex extended survival by 22% ? Am I mixing apples and oranges?

Schwah

[Tall_Allen in reply to Schwah]

True. But that is not what the OP asked.

[Shorehousejam in reply to Tall_Allen]

Hi, Would you possibly have the study link?

Is it possible that the Non steroidal anti-inflammatory drug Celebrex , may of contributed to the 22% increase in the survival rate and that it also affects QOL by treating pain.

[Tall_Allen in reply to Shorehousejam]

Only the combination worked (neither alone added to survival), and it was in men who were newly diagnosed and metastatic.

ascopubs.org/doi/10.1200/JC...

[Seasid in reply to Shorehousejam]

Celebrex could negatively impact your heart.

I also gave up with the idea taking zoledronic acid as I may need psma treatment in the future and for that purpose Denosumab is recommended.

Therefore I will stick to Denosumab if I will need it in the future.

I went through the study briefly and it was not clear to me that 22% survival benefit. I definitely would not risk damaging my heart with that medication (Celebrex).

[Seasid in reply to Seasid]

I just googled it:

bing.com/search?q=celebrex+...

Celebrex heart issues. It could shorten your life, not extend it.

[Shorehousejam in reply to Seasid]

Thank you, not interested in injected these agents if at all possible

[Shorehousejam in reply to Seasid]

I’m interest more in the estrogen patches. I have to investigate that more.

Denosumab is a bone anti-resorptive drug used for the treatment of the following: FDA-approved Indications. Prevention of skeletal-related events (e.g., bone pain and fractures) secondary to multiple myeloma or bone metastases from solid tumors. Used in conjunction with treatments for primary malignancy[1]

I have lytic lesions which multiple myeloma is notorious for.

[Grandpa4]

I think their value is in treated skeletal events caused by the tumors. There are fewer fractures at tumor sites. The fracture are obviously very painful.

[Shorehousejam in reply to Grandpa4]

Understandable so

[MateoBeach]

Why I take denosumab (besides already correcting my osteopenia):

ncbi.nlm.nih.gov/pmc/articl...

"Targeting bone metastases in prostate cancer (PCa) is a major goal since bone metastases are present in >90% of advanced PCa patients causing significant morbidity and mortality (1). Treatment strategies used for “bone targeted” therapies including bisphosphonates and radionuclides mainly focused on the treatment of existing bone metastases and were not deemed to delay the development and formation of new bone metastases. Preclinical evidence suggests that the RANK-Ligand plays an important role for the development of bone metastasis by influencing cell migration and the tissue-specific metastatic behavior of cancer cells. Targeting the RANK-Ligand may therefore be effective in preventing the development of new bone metastases in prostate cancer patients (2). Denosumab is a monoclonal antibody that binds the RANK-Ligand thereby inhibiting interaction with its receptor on the cell surface of osteoclasts and prostate cancer cells. After demonstrating efficacy in the prevention of treatment induced bone loss and prevention of skeletal related events, denosumab has already been licensed for the treatment of prostate cancer patients (3,4). Most recently, the results of a phase-III clinical trial investigating the effects of denosumab on the development of bone metastases have been published (5). The trial recruited 1,432 patients to randomly receive either denosumab (120 mg s.c. 4-weekly) or placebo. Patients with castration-resistant prostate cancer and a high risk of developing bone metastases (i.e. PSA >8 ng/mL and/or PSA doubling time <10 months) were included into the trial. Treatment was continued until occurrence of bone metastases as evidenced by bone scan that was confirmed by a second imaging modality (CT, MRI or plain radiography). Patients were then taken off study and treated per investigator discretion to receive standard treatment for bone metastasis.

Primary endpoint of the trial was bone-metastasis-free survival, as determined by time to first occurrence of bone metastasis (symptomatic or asymptomatic) or death from any cause. Secondary endpoints included time to first bone metastasis and overall survival. The results showed that denosumab significantly improved bone-metastasis-free survival by 4.2 months compared to placebo [HR 0.85 (95% CI: 0.73-0.98), P=0.028]. Median time to first bone metastasis was 29.5 (95% CI: 25.4-33.3) and 25.2 (95% CI: 22.2-29.5) months with denosumab and placebo, resulting in a risk reduction of 15% [HR 0.85, (95% CI: 0.73-0.98), P=0.028] for the development of bone metastasis (Figure 1). Furthermore time to first bone metastasis improved significantly (33.2 vs. 29.5 months, HR 0.84 with P=0.032) and denosumab led to a 33% reduction in the risk to develop symptomatic bone metastasis (HR 0.67, P=0.01). There was no difference in the time to overall prostate cancer progression (22.4 vs. 21.9 months, P=0.13) and median overall survival (43.9 vs. 44.8 months, P=0.91) between treatment groups. Overall toxicity and the rate of serious adverse events did not differ significantly, although patients receiving denosumab showed a higher incidence for osteonecrosis of the jaw (5%, any grade) and hypocalcemia (2%, any grade)."