I have been on Lynparza since June 1, 2024. Had to lower dosage after 3 months to reduce SEs, especially constant fatigue.
Point of this post is supplements. My bone and liver profiles are both ok. But red blood cells are down (Hg) and MCV too high, despite iron in diet. Am considering B12 supplements. I agree with the general need to prefer getting nutrients from diet, but would nevertheless appreciate any comments or suggested alternatives on this case.
lan99, not to worry too much, but a concern. After my radiation, I had a similar situation. Finally my PCP referred me to a hemotologist who did a bone marrow biopsy. Bad news. It was myelodysplastic syndromes with ring sideroblasts (MDS-RS). It is a blood cancer caused by the radiation. It is rare, but I feel way underdiagnoised considering all the co-morbidities we have. Google it.
Thanks. I googled it, is indeed worrying. Not ready for bone marrow biopsy yet but will keep this scenario in mind.
Hello! What kind of radiation that caused blood cancer? Radium 223?
Don't know the answer to your question, but mine was from my SBRT sessions. I would think that any kind of radiation or chemotherapy could cause it. Again, it is rare, but all of us need to know everything we can about this beast.
Been on Lynparza since December 2023. I am currently on half dose until blood work next week. I too suffer from low blood cell count. I have done B12 injections twice a week since February. Doesnt seem to help me. But, may be worth a try
B12 probably won't help. PARP inhibitors interrupt the biochemical mechanism that creates new red blood cells.
Thanks TA. I have the impression it is still early days for Lynparza. Hopefully a more targeted version will be available before long.
There are more selective PARP inhibitors that target only PARP1 that doesn’t interfere with red blood cell production.
onclive.com/view/parp1-sele...
Below are the trials (from ChatGPT)
Several clinical trials are currently investigating saruparib (AZD5305), a selective PARP1 inhibitor, to evaluate its efficacy and safety across various cancer types. Notable studies include:
1. EvoPAR-Prostate01 (NCT06120491): A Phase III, randomized, double-blind trial comparing saruparib combined with a physician’s choice of new hormonal agents (NHAs) against placebo with NHAs in men with metastatic castration-sensitive prostate cancer. The primary objective is to assess radiographic progression-free survival. 
2. EvoPAR-Breast01 (NCT06380751): This Phase III, open-label study evaluates saruparib plus camizestrant versus a physician’s choice of CDK4/6 inhibitors combined with endocrine therapy or camizestrant alone in patients with BRCA1, BRCA2, or PALB2 mutations and hormone receptor-positive, HER2-negative advanced breast cancer. The main goal is to determine the efficacy of these combinations in the first-line treatment setting. 
3. PETRA Trial (NCT04644068): A Phase I/II study assessing the safety, tolerability, and preliminary efficacy of saruparib as monotherapy and in combination with other anti-cancer agents in patients with advanced solid tumors harboring homologous recombination repair deficiencies. Early results have shown promising anti-tumor activity with a favorable safety profile. 
4. ASCERTAIN Study (NCT05169437): This Phase I trial investigates the biological effects of saruparib alone, darolutamide alone, and their combination when administered prior to radical prostatectomy in men with newly diagnosed prostate cancer. The study aims to understand the treatments’ impact on prostate cancer biology before surgical intervention. 
These trials are crucial in determining saruparib’s potential benefits and safety across different cancer types and patient populations.
TA is there a reason to continue PARPi if it is interrupting bone marrow production? It seems counter intuitive since one will certainly need their bone marrow to produce immune cells.
It has proven to extend survival if men are BRCA+.
My original testing showed no actionable mutations. After castrate resistance, additional testing showed I had acquired BRCA, BRCA2, and ATM. MO was encouraged and started me on Lynparza. I had no blood work side effects; but had some leg cramping and fatigue. Drug is completely ineffective for me, discontinuing and moving on. Her best guess is because they are acquired mutations. Best of luck to others, there is a lot of hope to these drugs.
Interesting. Mine is acquired. This is the first I hear of a possible difference in the effectiveness of the drug in this context.
In trials, half were innate, half acquired. It worked equally well in both. Perhaps the new generation of PARP inhibitors will work better for you, like Module 5 of the trial below:
i know this pist is two months ago but in reading your bio did you ever get on that
clinical trial BMS 986460
I did six months of the trial and went to the full dose. The drug had no effect on me at all. Subsequent genetic testing revealed that for me it was never going to work. None of the ARPI drugs worked, so an androgen receptors degrader wouldn't either. According to the trial Dr, it was working well for others. The precursor drug to this trial has gone on to Phase 2.
So does this mean you are neuroendicrine? Or do you have a glucocorticoid receptor mutation driving your canc?
MO has ruled out neuroendocrine. Honestly have never heard of the glucocorticoid receptor mutation. I'll certainly ask next appt.
Here is a great article
Targeting signaling pathways in prostate cancer: mechanisms and clinical trials
pubmed.ncbi.nlm.nih.gov/357...
Also look at the similar and cited by articles. They are very important to get an understanding of your disease at present.
My oncologist, Dr. Sartor at Mayo warns against B12, he says prostate cancer loves it.
Ed
Many thanks! You and TA have convinced me to back off this idea.
Can you test your B12 level?
I have 32 items tested of which 14 under Red Blood Cells. Cannot see B12. Is it known by another name?
Here is a good article on B12 and other nutrients/supplements and prostate cancer.
wcrf.org/research-policy/ou....
Aims and objectives
Based on our previous work and other research, we think that folate, vitamin B12, and iron may increase prostate cancer risk or progression, and that selenium, vitamin D, vitamin E and lycopene may protect against prostate cancer risk or progression. Our objective is to determine whether these and other nutrients cause prostate cancer by exploiting natural genetic variation.
We will also collate all the evidence from human and animal studies that look at the mechanisms by which body size and vitamin D lead to advanced prostate cancer to determine the biological pathway by which these risk factors may be operating.
never heard of the connection between b12 and prostate cancers loving it. Any background info on this subject. I too recently started on lymparza. Psa is dropping steadily since starting but I too see my blood counts dropping as well. I’ve been taking a b complex vitamin and zinc supplements but still see the same side effects. I’ve only been on for 2 months and was hoping the side effects level out a bit. Would love to hear of others experiences with this drug in longer term use. Anybody out there?
No background info, if Sartor tells me not to take it I listen, he is among the top PCa docs in the country.
Ed
Sartor is one of the best Radiopharmaceutical Oncologists but he is not trained in nutrition. That my fellow warrior is letting the blind lead the blind.
Dr Sartor is way to busy to study nutrition and way to valuable in Radiopharmaceuticals to venture into nutrition.
I did the first 3 months at full dosage 600mg/day. I was in bed by the end but the PSA dropped 61 to 47. I had to reduce dosage to 400 then 200 before I got some relief. Am unlikely to be getting much benefit from 200/day so need to ramp this up to a level I can tolerate while still getting benefit.
What dosage are you on ?
My PSA was 26. Started on lymparza and was blood tested every week for first 4 weeks. It started to drop in week 4. Today at week 8 PSA is 16.4. Dosage is 400 mg / day. Had a tough time at first with se but has kinda eased up for me. Still fatigue and sweats. Blood work , particularly wbc and rbc counts are low and continue to fall. Anemia is my concern now. I feel good, exercising and eating well. Looking for something in the immunotherapy line that could work for me while I ride this wave. Just had biopsy done. Awaiting results from pathology.
I am stuck taking omeprazole, a stomach acid reducer, for GERD/reflux. For this reason I take B12 supplement sublingually.
Lynparza can be used for treatment when there’s DNA damage. How about without the DNA damage?
I believe it is too toxic to take it without the BRCA genetic mutation. FDA didn't approve its use without the BRCA genetic mutation for that reason.
Maybe for short time in combination with radiation treatment or maybe chemotherapy?
I didn’t take Lynparza after hearing some negative outcomes for those without the BRCA genetic material. Thanks for your kind input.
What do you think about short use of parp inhibitors combined with SBRT radiation? During SBRT radiation it could be useful?
Combining PARP inhibitors with SBRT radiation is an emerging area of interest in cancer therapy, particularly for prostate cancer and other cancers with DNA repair deficiencies. Here's an overview of how this combination could work and what to consider:
Rationale for Combining PARP Inhibitors with SBRT
1. Mechanism of Action Synergy:
SBRT delivers high doses of radiation to a precise area, causing double-strand DNA breaks in cancer cells.
PARP inhibitors (like olaparib or rucaparib) block the repair of single-strand DNA breaks. When these single-strand breaks accumulate, they can evolve into double-strand breaks, which are lethal to cells, especially those with DNA repair defects (e.g., BRCA1/2 mutations).
2. Enhanced Tumor Kill:
By using PARP inhibitors, cancer cells are less able to repair radiation-induced DNA damage, increasing the likelihood of cell death.
This combination can be particularly effective in tumors with homologous recombination repair (HRR) deficiencies.
3. Potential to Sensitize Tumors:
PARP inhibitors may sensitize tumors to radiation, potentially allowing for better control of the disease even in difficult-to-treat sites.
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Timing and Short-Term Use During SBRT
During SBRT: Using PARP inhibitors during the course of radiation could amplify the DNA damage caused by SBRT. This timing leverages the radiosensitization properties of PARP inhibitors.
Short-Term Use: Short courses of PARP inhibitors (initiated shortly before and continued during SBRT) could provide the synergistic benefit without prolonged exposure to the drugs, thereby reducing the risk of side effects like fatigue, anemia, or nausea.
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Clinical Considerations
1. Eligibility:
Best suited for patients with BRCA1/2 or other HRR gene mutations, as these patients derive the most benefit from PARP inhibitors.
For non-HRR-mutated cancers, the benefit might be less pronounced but is still being investigated.
2. Toxicity:
Combining PARP inhibitors and SBRT may increase side effects like gastrointestinal or hematologic toxicity. However, short-term use can mitigate these risks.
Close monitoring by your medical team is essential.
3. Evidence:
While preclinical studies and some early-phase clinical trials show promise, larger randomized trials are still needed to establish the safety and efficacy of this combination definitively.
4. Availability:
Discuss with your oncologist if this combination is feasible and whether any clinical trials are available that align with your case.
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Conclusion
Combining PARP inhibitors with SBRT radiation during treatment could be a highly effective, innovative strategy, especially for cancers with HRR deficiencies. Short-term use might optimize benefits while minimizing risks. However, this approach should be carefully tailored to your specific cancer type, genetic profile, and overall treatment goals. Collaboration between your radiation oncologist and medical oncologist is crucial to ensure the best outcome.
Would you like details about specific trials or examples of cases where this combination has been successful?
ChatGPT said
I’m ready to go for Radium 223 in two weeks time. Hopefully it will go well with my red blood count.
Supplements for metastatic prostate cancer 
Your covid prevention tip?
Recommendations for additional supplements?
Need some guidelines regarding supplements
Please share protocols, diet, repurposed or natural supplements for aPC!
