Xgeva

[Zavulon1945]

Alkaline phosphates over three months from 112 to 202. Is Xgeva not working anymore?

[Tall_Allen]

That has nothing to do with Xgeva. Xgeva only improves your bone mineral density.

[Professorgary in reply to Tall_Allen]

Well then maybe you could explain why the first blood test after Xgeva my alp in in the 60s the next month it is in the 70s and the last test immediately before my injection it is in the 80s. I get an injection every three months.

[Tall_Allen in reply to Professorgary]

Any medication can add to liver toxicity. ALP can also increase when bone mets are active. It doesn't mean Xgeva is not working. Xgeva is only taken to improve bone mineral density.

[Zavulon1945 in reply to Tall_Allen]

Thank you.

[Seasid]

A rising alkaline phosphatase (ALP) level over three months could indicate increased bone turnover, which may be due to several factors, including disease progression, healing fractures, or an inflammatory response. While Xgeva (denosumab) is used to prevent skeletal-related events in bone metastases, a rising ALP alone does not necessarily mean it is no longer effective.

A few things to consider:

Disease Progression: If the underlying cancer is affecting the bones more aggressively, Xgeva may not be sufficient to control bone turnover. Imaging (bone scans, PET/CT) can help assess this.

Healing or Bone Remodeling: If you had recent bone lesions or fractures, ALP can rise temporarily as part of the healing process.

Other Causes: Liver issues, vitamin D deficiency, or other bone disorders can also increase ALP levels.

It would be best to discuss this trend with your oncologist, who may recommend additional imaging or blood tests (such as bone-specific ALP) to better assess the cause. Are you experiencing any new bone pain or other symptoms?

ChatGPT said

[Zavulon1945 in reply to Seasid]

No bone pain, but the metastases have clearly grown. However, their growth did not stop even at PSA <0.03.

[Seasid in reply to Zavulon1945]

Tall_Allen is partially correct in that Xgeva (denosumab) primarily works to prevent bone loss and fractures by inhibiting osteoclast activity. However, its role extends beyond just improving bone mineral density—it helps reduce skeletal-related events (SREs) in patients with bone metastases.

Your rising ALP levels could be due to multiple factors:

Bone Metastases Activity: If cancer in the bones is progressing, ALP may increase as a response to increased bone turnover.

Bone Healing: If there was recent bone damage, such as micro-fractures or healing metastases, ALP could temporarily rise.

Liver Function: ALP is also produced by the liver, so liver function tests (GGT, ALT, AST) can help determine if the increase is bone-related or hepatic.

Denosumab's Mechanism: Xgeva inhibits osteoclasts, which could alter bone remodeling dynamics, sometimes leading to transient ALP changes.

It would be best to correlate ALP trends with imaging (bone scans or PET/CT) and other markers like PSA and bone-specific ALP to get a clearer picture. Are you experiencing any new or worsening bone pain?

ChatGPT said

[Seasid in reply to Zavulon1945]

It can be confusing when imaging shows clear progression of bone metastases even though your PSA remains very low. Here are some key points to consider:

PSA and Tumor Activity

PSA Limitations: PSA is produced by prostate cancer cells, but in some advanced cases the cancer can evolve and lose the ability to secrete PSA. This means that even when PSA levels are low, tumor growth can still occur.

Tumor Heterogeneity: Some prostate cancer cells may become less dependent on the pathways that produce PSA (or androgen signaling), leading to what's sometimes called a "PSA-negative" progression.

Role of Xgeva (Denosumab)

Mechanism of Action: Xgeva is designed to strengthen bone and reduce the risk of skeletal complications by inhibiting osteoclast activity. It is not an anti-tumor agent and does not directly control the growth of cancer cells.

Skeletal-Related Events: Its benefit lies in reducing bone pain, fractures, and other skeletal-related events rather than halting the progression of metastases.

What This Means for You

Progression Despite Low PSA: The growth of metastases despite a PSA <0.03 suggests that the tumor might be progressing independently of PSA production. This phenomenon is seen in some patients with advanced disease.

Further Evaluation: Since imaging shows that the metastases are growing, it might be necessary to re-assess your overall treatment plan. Your oncologist may consider additional treatments that target the tumor cells directly, such as chemotherapy, hormonal therapies, or novel targeted treatments.

Discussing these findings with your medical team is important to determine if additional or alternative treatment strategies are needed. They might also look into other markers (like bone-specific alkaline phosphatase or other imaging modalities) to get a clearer picture of your disease status.

ChatGPT said

[Zavulon1945 in reply to Seasid]

Thank you so much for your detailed advice. Unfortunately, there is no personal team in Germany. Even in a big center. The doctors change. If you see one today, you will see another one tomorrow. Maybe it's just me.

[Seasid in reply to Zavulon1945]

Could you be treated at the Heidelberg University?

[Zavulon1945 in reply to Seasid]

That's where I've been lately.

[Seasid in reply to Zavulon1945]

Could you ask for guardant 360 cdx liquid biopsy in order to see if you have actionable genetic mutations?

[Zavulon1945 in reply to Seasid]

That's what we were talking about. A biopsy. I don't know what kind. But the biopsy wasn't scheduled until after the second Pluvicto injection.

[Seasid in reply to Zavulon1945]

Liquid biopsy is just a simple blood draw while the tissue biopsy is more like an operation, they take a tissue sample from your metastasis and analyse it.

[Seasid in reply to Seasid]

What is your current PSA?

[Zavulon1945 in reply to Seasid]

The PSA will not be known until March 28. Before the first dose of Pluvicto - March 11 PSA=5.8.

[Zavulon1945]

No new pains. No growing pains either. But the increase in phophatase coincided with the rise in PSA.