Lu-177 or Cabazitaxel

My dad has taken Zytiga for 1 year even though it’s not really work. His current PSA is greater 34, CT scan shows that metastasis is unchanged in comparison to the time he took docetaxel (PSA ≈ 0.29, please see my dad profile for details). However, he sometimes feels hurt/uncomfortable at leg and/or hip. Due to limitation of treatments in my country, his doctor suggests him change to Xtandi (self-payment). We don’t want to take that option at this moment due to the concern of cross-resistance. We prefer Cabazitaxel or Lu177 at countries around Vietnam. Through Healthunlocked, we heard about Lu177 and Dr. Ishita Sen and contacted her to find out chances of treatment for my dad. I would like to ask for your advice who has experience.

- When he needs to stop Zytiga if my dad decides to take Lu177? 1 week, 2 weeks or he can take it until the last day before taking Lu177?

- One of Lu177 side effects is mouth dry. Do you know any tip to reduce this side effect? Besides it, are there any significant side effects?

- From your knowledge, my dad should take Lu177 or Cabazitaxel next? My dad experiences ATD, Docetaxel and Zytiga.

- Please share if you have any other thought

Thanks you in advance for your sharing,

[Ramp7]

I can only speak from my own experience, going for 3rd infusion this week. Prior to first infusion, Zytiga was stopped, still taking Lupron (3 month). No ill side effects such as you mention from LuPSMA617. For me, well tolerated. Godspeed

[Hidden in reply to Ramp7]

Thank you for sharing & Good luck with your treatment

[Hidden in reply to Ramp7]

Hi Ramp7, do you mean you stop taking Zytiga before you started Lu177 and also don't use it during the intervals of infusions? Thank you

[Ramp7 in reply to Hidden]

Zytiga was completely stopped. I believe the feeling was it was no longer effective. I still go for my Lupron 3 month shot to keep T levels very low.

[Hidden in reply to Ramp7]

Thank U

[MateoBeach]

Dr. Ishita Sen is excellent to consult regarding possible Lu-PSMA treatments in Dehli. She also posts in this APC forum so you could PM her. Your father should obtain a PSMA PET scan first and send reading or disc copy to her to review. She provides virtual are email consultation.

[Hidden in reply to MateoBeach]

Thank you for response. I have PM her. PSMA scan isn’t available in Vietnam so we have to take it in India or a country around Vietnam. One of my concern is whether my dad should take Lu177 or Cabazitaxel first. Maybe there aren’t many people experience both of them but I’m still look forward to receiving your sharing

[MateoBeach in reply to Hidden]

In general terms, most experienced sites found that Lu works better when used earlier. And it can help restore response to advanced androgen drugs such as enzalutamide and probably others. However, cabazitaxel can also be a very good choice, especially if that is more available there. We must be practical in choosing our best sequencing.

[Hidden in reply to MateoBeach]

Thank you for your sharing. Unfortunately, Cabazitaxel also isn’t available in Vietnam. Is Lu177 a better option in this case?

[slpdvmmd]

At Heidelberg they did not have me stop my zytiga. This abstract may also help guide you.Lancet

. 2021 Feb 27;397(10276):797-804. doi: 10.1016/S0140-6736(21)00237-3. Epub 2021 Feb 11.

[ 177 Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial

Michael S Hofman 1, Louise Emmett 2, Shahneen Sandhu 3, Amir Iravani 4, Anthony M Joshua 5, Jeffrey C Goh 6, David A Pattison 7, Thean Hsiang Tan 8, Ian D Kirkwood 9, Siobhan Ng 10, Roslyn J Francis 11, Craig Gedye 12, Natalie K Rutherford 13, Andrew Weickhardt 14, Andrew M Scott 15, Sze-Ting Lee 15, Edmond M Kwan 16, Arun A Azad 3, Shakher Ramdave 17, Andrew D Redfern 18, William Macdonald 19, Alex Guminski 20, Edward Hsiao 21, Wei Chua 22, Peter Lin 23, Alison Y Zhang 24, Margaret M McJannett 25, Martin R Stockler 26, John A Violet 3, Scott G Williams 3, Andrew J Martin 27, Ian D Davis 28, TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group

Collaborators, Affiliations expand

PMID: 33581798 DOI: 10.1016/S0140-6736(21)00237-3

Abstract

Background: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers β radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer.

Methods: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428.

Findings: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [177Lu]Lu-PSMA-617.

Interpretation: [177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel.

[Hidden in reply to slpdvmmd]

That is a very informative article. Thank you

[j-o-h-n]

Hope whatever you choose first helps your dear Dad. Regards and God Bless.

Good Luck, Good Health and Good Humor.

j-o-h-n Monday 04/04/2022 12:40 PM DST

[Hidden in reply to j-o-h-n]

Thank j-o-h-n