Restarting anti androgens after chemo

[roboocme]

My husband has completed two years of chemotherapy, followed by Pluvicto. Would it be possible to re-start an anti-androgen ( Zytiga, daralutimide) as therapy? What choices does he have going forward?

[vintage42]

It would be helpful to add a bio showing his age and his cancer and treatment history.

[dhccpa]

My understanding is that chemo CAN "rejuvenate" an anti-androgen that was failing, but double check me on that.

[Ian99 in reply to dhccpa]

I have noted from prior reading that if Xtandi begins to fail, start Docetaxel. Per the PRESIDE trial, this could also have the effect of prolonging Xtandi effectiveness.

[j-o-h-n]

Would you please be kind enough to update your dear husband's bio. All information is voluntary but it helps us help him/you and helps us too. Thank you!!!

Good Luck, Good Health and Good Humor.

j-o-h-n

[leo2634]

I have only been on Zytiga Eligard since 2018 never had chemotherapy or any other treatments other than Provenge infusions back in 2019.

[CAMPSOUPS]

Good question and of course good MO can best answer it.

Hard to ponder without a bio on your part though.

If the cancer burden is low now (PSA and scans look decent) and you are wondering about introducing the 2nd generation hormonals' again when progression returns its an interesting thought. My layman brain says there have been 2 opportunities for cross resistance to be reduced-the chemo and the Pluvicto but just don't know if retreating with 2nd gens weighs on the positive side of benefit or not in this case.

[Seasid in reply to CAMPSOUPS]

The comment suggests that someone with a history of cancer treatment is considering reintroducing second-generation hormonal therapies after experiencing some level of cancer progression. The writer acknowledges that chemotherapy and Pluvicto (a radioligand therapy) may have reduced the risk of cross-resistance, but they are unsure whether reusing these hormonal treatments would be beneficial in this specific situation.

The decision to reintroduce second-generation hormonal therapies, such as Abiraterone or Enzalutamide, often depends on various factors like the patient’s current cancer burden, previous treatment responses, and the overall clinical picture. In cases where the cancer burden is low and previous treatments like chemotherapy and Pluvicto have potentially reduced resistance, reintroducing these agents might be considered. However, this is a complex decision that ideally requires input from a medical oncologist (MO), who can evaluate the nuances of the case, including potential benefits and risks.

[CAMPSOUPS in reply to Seasid]

Hey brother. Poster's comment here intended for you.

Take care

roboocme profile imageroboocme in reply to CAMPSOUPS

1 hour ago

I can't thank you enough Seasid for your thorough and very thoughtful response. My husband has not had a PSA measure since completing his sixth Pluvicto treatment at the end of July. His OC said it was important to wait for several weeks to see how the full treatment reacts. He had a rise in PSA and then a plateau during the six cycles. I plan to ask his OC about the many suggestions you made. Again, you are a marvelous source of information. I would like to contact you again, if I have more questions.

[roboocme in reply to CAMPSOUPS]

I can't thank you enough Seasid for your thorough and very thoughtful response. My husband has not had a PSA measure since completing his sixth Pluvicto treatment at the end of July. His OC said it was important to wait for several weeks to see how the full treatment reacts. He had a rise in PSA and then a plateau during the six cycles. I plan to ask his OC about the many suggestions you made. Again, you are a marvelous source of information. I would like to contact you again, if I have more questions.

[Seasid in reply to roboocme]

You should also download the ChatGPT application and start using it.

My sister is a doctor and she was angry at me that I didn't instructed her to download the AI application earlier.

She realised that not everything is correct what ChatGPT say, but it is still very useful to learn about lots of things and to start talking to your oncologist by asking questions.

[Seasid in reply to roboocme]

I'm glad I could help, and I'm always here whenever you have more questions. It's good that you're discussing all the options with your husband's oncologist; having a thorough conversation will help in making the best possible decisions for his treatment. Please feel free to reach out anytime you need more information or support. Wishing you both the best as you continue this journey.

[Seasid]

What could be a better strategy to go forward in this particular situation?

[Seasid in reply to Seasid]

In a situation where a patient with prostate cancer is considering reintroducing second-generation hormonal therapies after previous treatments like chemotherapy and Pluvicto, the strategy should be carefully tailored to the patient's current clinical status and prior treatment history. Here’s a possible approach:

### 1. **Evaluate the Current Cancer Burden:**

- **PSA Levels and Imaging:** First, assess the latest PSA trends and imaging results (e.g., PSMA PET/CT). If the cancer burden is low and progression is minimal, there may be time to consider the best strategy without rushing into treatment.

- **Biomarker Analysis:** Consider additional biomarkers (e.g., AR-V7, BRCA mutations) to understand the tumor’s current sensitivity to hormonal therapies and other targeted treatments.

### 2. **Consider Timing for Reintroduction of Hormonal Therapy:**

- **Sequential Therapy:** Some experts advocate for a break in second-generation hormonal therapies before reintroducing them, particularly after a substantial response to chemotherapy or radioligand therapy. The aim is to potentially resensitize the cancer to these drugs.

- **Cross-Resistance Consideration:** Given that chemotherapy and Pluvicto may have reduced the potential for cross-resistance, it might be feasible to reintroduce second-generation antiandrogens. However, monitoring closely for effectiveness and resistance markers would be essential.

### 3. **Explore Combination or Alternative Therapies:**

- **Combination Approaches:** If resistance to second-generation antiandrogens is a concern, combining them with other agents (e.g., PARP inhibitors like olaparib if BRCA mutations are present) could be an option.

- **Alternative Agents:** Depending on the molecular profile of the tumor, other treatment avenues such as immunotherapy, clinical trials, or even newer hormonal agents could be explored.

### 4. **Maintain Close Monitoring:**

- **Regular Follow-Up:** Given the complex nature of treatment at this stage, frequent monitoring of PSA levels, imaging, and clinical symptoms is critical to detect any signs of progression early.

- **Adjustments Based on Response:** Be prepared to adjust the treatment plan based on how well the cancer responds to reintroduced therapies. If resistance develops, alternative strategies should be considered promptly.

### 5. **Consultation with a Multidisciplinary Team:**

- **Expert Input:** In complex cases, a multidisciplinary team approach, including input from medical oncologists, radiologists, and potentially a tumor board, could help in making the most informed decision.

### 6. **Patient-Centered Decision Making:**

- **Quality of Life Considerations:** It’s crucial to weigh the potential benefits of reintroducing these therapies against their impact on quality of life, especially if side effects are a concern. Patient preferences should be a central part of the decision-making process.

This strategy balances the potential benefits of reintroducing hormonal therapy with the need for careful monitoring and a readiness to adapt based on how the cancer responds. Engaging in a detailed discussion with the treating oncologist would be essential to tailor the plan to the individual’s specific situation.

[Seasid]

What are the best options? The patients already had 2 years of chemotherapy and Pluvicto?

[Seasid]

Given the patient's extensive treatment history, including two years of chemotherapy and Pluvicto (Lutetium-177-PSMA therapy), the best options going forward should be carefully chosen based on several factors, including the patient’s current clinical status, previous responses to treatment, and overall health. Here are some of the most viable options:

### 1. **Re-challenge with Second-Generation Hormonal Therapies:**

- **Enzalutamide or Abiraterone:** If the patient previously responded well to these therapies before developing resistance, and there’s been a significant interval since their last use, re-challenging with one of these agents might be an option. The potential benefit here hinges on the possibility that prior treatments (chemo and Pluvicto) have resensitized the cancer to hormonal therapy.

### 2. **PARP Inhibitors:**

- **Olaparib or Rucaparib:** If the patient has a DNA repair gene mutation (e.g., BRCA1/2, ATM), PARP inhibitors could be highly effective. These agents have shown promise in patients with prostate cancer who have specific genetic mutations, especially in the context of prior therapies.

### 3. **Immunotherapy:**

- **Pembrolizumab:** If the patient’s tumor exhibits high microsatellite instability (MSI-H) or a high tumor mutational burden (TMB), pembrolizumab (an immune checkpoint inhibitor) could be considered. While not commonly effective in prostate cancer, it has shown benefit in a subset of patients with these specific biomarkers.

### 4. **Switching to a Different Hormonal Agent:**

- **Darolutamide or Apalutamide:** If the patient has already used Enzalutamide or Abiraterone, switching to a different second-generation antiandrogen like Darolutamide or Apalutamide might offer some benefit. These agents have slightly different mechanisms and may overcome resistance in some cases.

### 5. **Clinical Trials:**

- **Investigational Therapies:** Considering the patient's extensive treatment history, participation in a clinical trial might offer access to new and emerging therapies. Trials involving novel agents, combination therapies, or next-generation PSMA-targeted treatments could be particularly relevant.

### 6. **Radiopharmaceuticals or Radiotherapy:**

- **Repeat Pluvicto Therapy:** In some cases, additional cycles of Pluvicto may be considered if the patient initially responded well, though this depends on the cumulative dose received and overall tolerability.

- **Targeted Radiotherapy:** If the patient has a limited number of metastatic sites, stereotactic body radiotherapy (SBRT) could be used to control specific lesions.

### 7. **Chemotherapy Rechallenge or Alternative Chemotherapy:**

- **Cabazitaxel:** If the patient responded to prior docetaxel therapy but now shows progression, Cabazitaxel could be an option. It’s often used as a second-line chemotherapy for castration-resistant prostate cancer (CRPC).

- **Platinum-Based Chemotherapy:** If the patient has a DNA repair defect, a platinum-based chemotherapy regimen might be considered, though this is less commonly used in prostate cancer.

### 8. **Supportive Care and Symptom Management:**

- **Bone-Targeted Therapies:** If the patient has bone metastases, continuing or initiating treatment with bone-targeted therapies like bisphosphonates (e.g., Zometa) or Denosumab could help manage skeletal-related events.

- **Palliative Care:** Symptom management is crucial, particularly if the disease is advanced. Palliative care teams can help manage pain, fatigue, and other symptoms to improve quality of life.

### Considerations for Decision-Making:

- **Patient’s Overall Health:** The patient’s performance status, organ function, and any treatment-related toxicities should guide the choice of therapy.

- **Molecular Profiling:** Molecular testing to identify actionable mutations or resistance mechanisms can refine treatment options.

- **Quality of Life:** The impact of potential side effects on the patient’s quality of life should be carefully weighed against the expected benefits of the treatment.

### Conclusion:

The best options would likely involve a combination of reintroducing second-generation hormonal therapies, considering PARP inhibitors if applicable, exploring clinical trials, or even revisiting chemotherapy with agents like Cabazitaxel. These decisions should be made collaboratively with the patient and their oncology team, taking into account the full scope of their treatment history and current health status.

[Seasid]

Why is platinum based chemotherapy not common in PC setting?

[Seasid in reply to Seasid]

Platinum-based chemotherapy, such as cisplatin or carboplatin, is not commonly used in the treatment of prostate cancer (PC) for several reasons:

### 1. **Lack of Broad Efficacy:**

- **Tumor Sensitivity:** Prostate cancer generally shows limited sensitivity to platinum-based agents compared to other types of cancer, such as testicular cancer, ovarian cancer, or certain lung cancers. The mechanisms that make these other cancers responsive to platinum drugs are not as pronounced in most prostate cancers.

- **Genetic Mutations:** Platinum-based chemotherapy is particularly effective in tumors with defects in DNA repair mechanisms, such as BRCA1/2 mutations. While these mutations do occur in prostate cancer, they are relatively rare (found in approximately 5-10% of metastatic castration-resistant prostate cancer cases). Therefore, only a subset of patients might benefit from platinum-based treatments.

### 2. **Availability of More Effective Options:**

- **Standard Therapies:** There are already well-established, effective treatments for prostate cancer, including androgen deprivation therapy (ADT), second-generation hormonal therapies (like Abiraterone and Enzalutamide), taxane-based chemotherapies (like Docetaxel and Cabazitaxel), and radiopharmaceuticals (like Pluvicto). These treatments have shown greater efficacy in the broader prostate cancer population.

- **Hormonal Dependency:** Prostate cancer is largely driven by androgen signaling, and therapies that target this pathway have proven to be more effective than non-specific cytotoxic chemotherapy like platinum agents.

### 3. **Side Effect Profile:**

- **Toxicity:** Platinum-based chemotherapy is associated with significant side effects, including nephrotoxicity (kidney damage), ototoxicity (hearing loss), neurotoxicity (nerve damage), and severe myelosuppression (bone marrow suppression). Given that there are other less toxic and more effective treatments for prostate cancer, the use of platinum-based chemotherapy is often avoided unless there is a strong indication for its use.

- **Patient Tolerability:** Many prostate cancer patients are older and may have comorbidities that make the side effects of platinum-based chemotherapy particularly challenging to manage.

### 4. **Niche Role in Specific Cases:**

- **Targeted Use:** Platinum-based chemotherapy may be considered in specific scenarios, such as in patients with advanced, aggressive prostate cancer who have mutations in DNA repair genes (e.g., BRCA1/2, ATM). These patients are more likely to benefit from platinum agents, but this remains a niche indication.

- **Clinical Trials:** Ongoing research is exploring the role of platinum-based chemotherapy in combination with other agents (like PARP inhibitors) or in molecularly selected subgroups of prostate cancer patients. However, outside of these settings, its use is not standard.

### Conclusion:

In summary, the limited efficacy, significant toxicity, and availability of more effective treatments for prostate cancer have made platinum-based chemotherapy a less common choice in this setting. It is generally reserved for specific cases where there is a clear indication, such as the presence of certain genetic mutations that impair DNA repair.

[Seasid]

What's about BAT in combination with carboplatin chemotherapy?

[Seasid in reply to Seasid]

**Bipolar Androgen Therapy (BAT)** in combination with carboplatin chemotherapy is an emerging approach in prostate cancer treatment, particularly for cases where traditional therapies are no longer effective. Here’s an overview of this combination:

### **Bipolar Androgen Therapy (BAT):**

- **Concept:** BAT involves rapidly cycling between high and low levels of testosterone to "shock" prostate cancer cells. The theory is that this cycling can disrupt the cancer cells’ ability to survive in a low-androgen environment, potentially resensitizing them to further androgen deprivation therapy (ADT) or other treatments.

- **Clinical Evidence:** BAT has shown promise in some studies, particularly in men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on standard androgen receptor-targeted therapies (like Abiraterone or Enzalutamide). Some patients have experienced PSA declines and clinical benefit with BAT.

### **Carboplatin Chemotherapy:**

- **Use in Prostate Cancer:** As mentioned earlier, carboplatin is not a standard treatment for prostate cancer due to its limited efficacy in the general prostate cancer population. However, it can be effective in prostate cancers with DNA repair defects (e.g., BRCA mutations).

- **Rationale for Combination:** The combination of BAT with carboplatin is based on the idea that BAT could potentially resensitize cancer cells to carboplatin by inducing DNA damage and exploiting vulnerabilities in the cancer cells that are exacerbated by the fluctuating testosterone levels. This may be particularly beneficial in patients whose tumors have specific genetic alterations, like BRCA mutations or other DNA repair defects.

### **Potential Benefits of the Combination:**

- **Overcoming Resistance:** The primary goal of combining BAT with carboplatin is to overcome resistance to conventional therapies. BAT might make cancer cells more susceptible to the DNA-damaging effects of carboplatin, leading to better outcomes.

- **Dual Mechanism of Action:** BAT works by destabilizing androgen receptor signaling, while carboplatin induces DNA damage. This dual approach could be more effective against resistant cancer cells.

### **Clinical Research and Evidence:**

- **Ongoing Trials:** There are ongoing clinical trials exploring the combination of BAT with carboplatin and other chemotherapy agents. Early results are promising, particularly in patients with specific genetic profiles that make them more likely to respond to platinum-based chemotherapy.

- **Pilot Studies:** Some smaller studies have shown that the combination can lead to meaningful clinical responses in certain patients with mCRPC, especially those who have progressed on standard therapies and have DNA repair defects.

### **Considerations:**

- **Patient Selection:** The combination of BAT and carboplatin is likely to be most effective in a select group of patients, particularly those with genetic mutations that impair DNA repair. Comprehensive molecular profiling can help identify these patients.

- **Side Effects:** Combining BAT with carboplatin may lead to additive side effects, including those associated with high-dose testosterone cycling and the toxicities of carboplatin (e.g., myelosuppression, nephrotoxicity). Careful management of these side effects is crucial.

### **Conclusion:**

BAT in combination with carboplatin chemotherapy is an innovative approach that might offer benefits to a specific subset of prostate cancer patients, particularly those with advanced, resistant disease and certain genetic mutations. However, this strategy is still experimental and is typically explored within the context of clinical trials or as a consideration in cases where other treatment options have been exhausted. As with any novel treatment approach, it’s important for patients to discuss the potential risks and benefits with their oncologist, ideally within a multidisciplinary team setting.

[Seasid]

I just wish to add what I was told above the combination of BAT and carboplatin. You can stop carboplatin at some point and continue with BAT only if it is useful for you. My MO has a phase ii clinical trial with BAT plus carboplatin here in Sydney, Darlinghurst Australia.