Docetaxel didn't work, what's next?

[anscombethomson]

Hi there! My father (65M from Toronto) was diagnosed almost three years ago with prostate cancer and we're really starting to lose hope. This community seems so informed and caring, I'd appreciate any thoughts that you may have about my dad's diagnosis

In 2019, his PSA rose to 10.4 and then to 14.2, and he subsequently went to 15.6 in December 2019. He went on to have a repeat biopsy, and this confirmed adenocarcinoma of the prostate, Gleason score 4+5 with the presence of intraductal carcinoma and perineural invasion. Ten out of 20 cores were positive for cancer with an estimated proportion of prostatic tissue involved with tumor of 50 percent. CT scan of the abdomen October 2019 showed an enlarged heterogeneous prostate with likely seminal vesicle invasion bilaterally with multiple pelvic lymphadenopathies confirming the obturator lymph node as well. Bone scan in 2019 did not show any skeletal metastasis. In January 2020, he was commenced on LUPRON with a plan to continue that for several years and consider consolidative local radiotherapy to the prostate and pelvis if he responded. His PSA did drop to 0.23 in March 2020 but then began to rise again in the summer of 2020. He had restaging scans in April 2021. The bone scan was negative for metastasis. The prostatic mass had increased in size. There was also an increase in the pelvic lymph nodes. CT thorax suggested suspicious pulmonary lesions. He was commenced on ABIRATERONE and PREDNISONE May 25, 2021. CT CAP on December 23,2021, progression of hepatic metastatic disease and new metastatic left obturator lymph node. There are additional prominent inguinal, iliac and retroperitoneal lymph nodes.

Metastatic castrate-resistant prostate cancer to the liver (biopsied January 2022, poorly differentiated carcinoma, IHC consistent with prostate origin, no neuroendocrine component) and lymph node and lung involvement. He has germline mutation of BRCA 2 pathogenic variant.

Completed 7 cycles of Docetaxel chemotherapy (Feb 2022 - June 2022). Rising PSA and imaging had shown progression with intra-abdominal disease, and new lung involvement. Switched to cabazitaxel and has completed two cycles, needs to complete 8 more. Isn't tolerating it well.

Grade 1 neuropathy in feet. A lot of pain in the left butt cheek is caused by increasing left obturator lymph node. Any advice to help with that?

Thank you so much if you took the time to read this post! I really, really appreciate it. Please let me know if you need any more information! - Gabi

[tallguy2]

Your father is heavily pretreated, as am I. Adding carboplatin to the chemo would be standard of care if he can tolerate to two-drug combo. The alternative would be to seek out a phase 1 clinical trial. For example, Just today we read that “Dose-dependent anti-tumor activity was demonstrated with REGN5678 and cemiplimab (Libtayo) in patients with metastatic castration-resistant prostate cancer (mCRPC) in a phase 1/2 study (NCT03972657), according to preliminary results announced in a press release by Regeneron Pharmaceuticals, Inc.”

[anscombethomson in reply to tallguy2]

Thank you so much! I'll talk to his doctor about adding carboplatin.

[tango65]

If the cancer is BRCA 2 consult about initiating treatment with Olaparib or Rucaparib, a PARP inhibitor. Many of BRCA positive cancers respond to these drugs.

[lcfcpolo]

Hi. Other drugs that may help those with BRCA gene mutations are Niraparib, a PARP inhibitor and separately Lynparza (which appears to have had great results in Ovarian Cancer that is BRCA). If possible search this forum for more detailed information. Good luck and well done for supporting your Dad.

[Tall_Allen]

Add carboplatin?

[Hidden]

I have exactly the same diagnosis. Responds very well to Olaparib, 15 months without progression.

[anscombethomson in reply to Hidden]

That's great to hear, thank you!