The H. Lee Moffitt Cancer Center is advancing prostate cancer treatment with a Phase 2 trial combining adaptive androgen deprivation therapy (ADT) with docetaxel for metastatic castration-sensitive prostate cancer (mCSPC). This builds on a successful Phase 1b trial, which demonstrated the feasibility of tailoring intermittent ADT based on PSA and testosterone levels.
The Phase 1b study showed no radiographic progression at 12 months among participants and suggested that adaptive therapy could mitigate the toxicities of continuous ADT, such as fatigue and bone loss, while maintaining effective disease control.
The Phase 2 trial adds docetaxel to this adaptive approach, aiming to prolong the castration-sensitive phase of mCSPC and improve survival outcomes. By integrating chemotherapy into a patient-guided treatment model, this research seeks to optimize cancer management while enhancing patients’ quality of life.
why throw a toxic treatment into the mix when the current trial treatments are working and side effects are minimal. What happened to do know harm?
I wonder if they are taking/took biomarkers of somatic and germline prior to treatment and if they are doing it for participants that are failing/responding to treatment.
From your website
“The results were compelling. At 12 months, none of the 16 participants experienced radiographic disease progression, confirming the feasibility of this adaptive approach. Moreover, after a median follow-up of 26 months, the secondary endpoints—median time to PSA and radiographic progression—remained unreached, indicating durable disease control. Patients who achieved a complete response during the induction phase appeared to benefit most, and the intermittent therapy approach significantly mitigated the toxicities typically associated with continuous ADT.
Building on this foundation, the ongoing Phase 2 trial seeks to enhance the benefits of adaptive therapy by adding docetaxel, a chemotherapy agent known to extend survival in mCSPC. This trial adopts a similar patient-centric approach, using PSA responses to guide the timing and combination of treatments, which include LHRH analogs, androgen receptor signal inhibitors (ARSIs), and docetaxel. The hypothesis driving this study is that adaptive therapy, when combined with docetaxel, can prolong the castration-sensitive phase of stage IV prostate cancer, potentially delaying progression and further improving outcomes.
This second-phase study is designed as a single-arm trial, with all participants receiving the same adaptive treatment protocol. Inclusion criteria ensure the selection of patients who are likely to respond to the adaptive approach, such as those who achieve significant PSA reductions during a preliminary run-in phase. Regular monitoring ensures that the therapy is adjusted in real time to optimize both efficacy and tolerability”.
Thanks but no thanks! If it is working why put me through chemo?
Adaptive Androgen Deprivation Therapy (ADT) at Moffitt Cancer Center employs an innovative, evolution-based approach to treat metastatic prostate cancer. Traditional continuous ADT often leads to drug resistance and disease progression. In contrast, Moffitt’s adaptive therapy adjusts treatment based on individual patient responses, aiming to prolong the effectiveness of therapy and delay resistance.
Algorithm Overview:
1. Initiation of Treatment:
• Patients begin with standard ADT, typically using luteinizing hormone-releasing hormone (LHRH) analogs, combined with new hormonal agents (NHAs) such as abiraterone, enzalutamide, or apalutamide.
2. Monitoring Response:
• Prostate-Specific Antigen (PSA) levels and testosterone levels are regularly monitored to assess treatment effectiveness.
3. Treatment Adjustment:
• Treatment Interruption: Once a significant PSA decline is achieved (e.g., >75% reduction), ADT is temporarily halted.
• Resumption Criteria: ADT is resumed upon evidence of PSA progression or radiographic progression, with the specific regimen determined by the patient’s testosterone levels at the time of progression:
• If testosterone >100 ng/dL: Restart LHRH analog alone.
• If testosterone between 50-100 ng/dL: Restart NHA alone; add LHRH analog if <50% PSA decline is observed after 6 weeks.
• If testosterone <50 ng/dL: Restart combined ADT with both LHRH analog and NHA.
4. Cyclic Treatment:
• This cycle of treatment initiation, monitoring, and adjustment continues, with therapy being paused and resumed based on PSA and testosterone levels, until there is evidence of imaging progression while on combined ADT.
Clinical Outcomes:
Studies at Moffitt have demonstrated that this adaptive approach can significantly prolong the duration of the castration-sensitive phase in metastatic prostate cancer. For instance, a pilot clinical trial reported that patients undergoing adaptive therapy had a median time to progression of 33.5 months compared to 14.3 months with standard continuous treatment. Additionally, overall survival was extended, and patients spent approximately 46% of the time off treatment, reducing side effects and healthcare costs. 
This adaptive strategy is part of Moffitt’s broader efforts to utilize mathematical modeling and evolutionary principles to inform cancer treatment, aiming to improve patient outcomes through personalized therapy adjustments. 
At least the are leaning a little against the breeze of continuous ADT which we know is harmful. Agree the addition of chemo should be a backstop for those who might have significant progression and not a rigid protocol. Did they break out results for those who have higher testosterone recovery? Do those who do not have T recovery have an option for TRT to provide equivalent physiologic benefit?
BYW I am now 3 years on long cycle BAT with mHSPC with undetectable PSAs. (T >2000 on high T and <24 on ADT/darolutamide.). MB
”Absolutely---I did not get into the whole deal. In previous post, and in answer to others---I use the info from a European study of 1800 men.
These men were all undetectable with PSA's under 0.1--- in translation, monitoring the PSA every 30 days is crucial. What they looked for, and I do also, is 3 consecutive rises in PSA in the 2nd decimal. I.E. if you are on vacation, and lets say your nadir was 0.03, and stayed close----but when in 3 months it went to 0.04 to 0.05 to
0.06---the conclusion was that a BCR was in your near future. Also if the PSA doubled from 0.03 to 0.06 or more in a 3 month period--the same--that a BCR was in your future---and at these points it is time to pull the trigger and stop the vacation, and go back to what worked for you before.
This is not SOC---as some Docs. would prefer you to fail to a number that can be seen on a scan. But my preference is to not let the cancer cells to now have access, to the blood stream, or the lymph system, and to put them back to sleep/so to speak---which I call senescence.”
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Anyone on Nubeqa ? on triplicate therapy, Firmagon, Zytiga & Prednisone Started Docetaxel Chemotherapy no mention of Nubeqa DX 07/2022