A needle biopsy Oct 15, 2023 revealed that at least some of my metastatic prostate cancer in a lymph node had mutated to an aggressive small cell neuroendocrine prostate cancer. (notable for CDK N1B, RB1, Tp53 mutations. MSS, TMB low)
I had 4 cycles of carboplatin/etoposide chemotherapy, which ended in March 2024 because a CT scan with contrast indicated a net increase in tumor burden.
While I'm waiting for a HPN328 clinical trial slot to open, UCSF Drs Small and Aggarwal as well as my Kaiser doctors Eldredge and Harzstark recommend I start lurbinectedin as a second line bridge chemotherapy.
I'd very much like to talk with other men whose metastatic prostate cancer has mutated to small cell neuroendocrine prostate cancer, and especially anyone familiar with lurbinectedin chemotherapy.
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silver5
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I too have small cell / neuroendocrine prostate cancer. I am just beginning 1st line chemo carbo+etoposide.
This cancer is not well understood or studied. There is some crossover of treatments from small cell lung cancer which has similiar characteristics and more attention.
"Small-cell lung cancer (SCLC) is an aggressive lung cancer subtype with neuroendocrine differentiation diagnosed in more than 150,000 people worldwide each year.1,2 The 3-year survival rate for patients with extensive stage (ES) SCLC is 6%.3 The addition of immune checkpoint inhibitors atezolizumab or durvalumab to platinum and etoposide chemotherapy followed by maintenance therapy with checkpoint inhibitor alone as first-line treatment for SCLC has led to approximately 30% reduction in the risk of death and durable but modest survival gains for a small subset of patients with ES-SCLC.3,4 Available therapies are limited for the majority of patients with SCLC who relapse. Topotecan, the most widely used second-line agent globally, has limited efficacy and an unfavorable safety profile.5,6 Lurbinectedin, in 2020 became the first drug approval by the US Food and Drug Administration in over 20 years for second line, was conditionally approved on the basis of an objective response rate (ORR) of 35%; however, a randomized study failed to demonstrate OS benefit.7,8 No agent is specifically approved for third-line treatment of relapsed SCLC."
Lurbinectedin in prostatic small cell and neuroendocrine carcinoma.
Authors: Haley M Meyer, Rajitha Sunkara, Himisha Beltran, Emily Rothmann, Kevin Dale Courtney, Andrew J. Armstrong, Andrea Lipucci, Melissa L. Stanton, and Alan Haruo BryceAUTHORS INFO & AFFILIATIONS
Background: Lurbinectedin (L) is a novel inhibitor of oncogenic transcription that was granted accelerated approval by the Food and Drug Administration in June 2020 for the treatment of metastatic small cell lung cancer (SCLC) following disease progression on or after platinum-based chemotherapy (PBC). Prostatic small cell or neuroendocrine carcinoma (SC/NEPC) is a high-grade, invasive malignancy that accounts for < 1% of all prostate cancers. SC/NEPC is distinct from prostatic adenocarcinoma and behaves similar to SCLC. NCCN guidelines for SC/NEPC recommend following the SCLC treatment guidelines. Using these guidelines, L may be used as a second-line treatment in patients (pts) with SC/NEPC who progress on or after PBC. We aimed to characterize the baseline characteristics, clinical course and therapeutic outcomes of pts treated with L for SC/NEPC.
Methods: After IRB approval, 18 cases were gathered from 4 academic oncology centers. Baseline patient data, prior treatments and L treatment outcomes, including best radiographic and serologic responses, overall survival (OS), progression-free survival (PFS) and treatment toxicity were assessed. The Kaplan-Meier method was used to calculate OS and PFS from the L start date. Clinical benefit rate (CBR) included pts with complete response (CR), partial response (PR) and stable disease (SD) on imaging.
Results: At the time of first L dose, all had metastatic disease with 2-6 distinct sites of metastases, most commonly bone (14/18, 77.8%), lymph nodes (14/18, 77.8%) and liver (13/18, 72.2%); median age was 63.5 (Range: 53-84); 11 pts (61.1%) had an ECOG 0-1; 4 pts (22.2%) had an ECOG of 2-3. The median total number of systemic therapies administered prior to L was 4 (Range: 2-7). All pts received PBC prior to L. The most common dose of L prescribed was 3.2 mg/m2 every 21 days (15/18, 83.3%). Androgen deprivation therapy was administered in conjunction with L in 9 pts (50%). The median number of cycles of L was 5 (Range: 1-10). L was discontinued due to toxicity in 1 patient (5.6%), disease progression in 10 pts (55.6%), transition to hospice in 2 pts (11.1%), 3 pts (16.7%) died while receiving treatment (not due to L toxicity), and 2 pts (11.1%) remained on L at the time of data reporting. The median OS and PFS from date of first L dose was 6.01 months (0.23 – 16.69) and 3.35 months (0.16 – 7.79), respectively. CBR was 9/16 (56.3%) with partial response in 5 pts (31.3%), stable disease in 4 pts (25%), and progressive disease in 7 pts (43.8%). Two pts did not have post-treatment imaging available to assess response. There were no hospitalizations for L treatment related adverse events (tRAE). The most common tRAE were grade I and II fatigue and anemia; 9 pts (50%) experienced no tRAE. The only grade IV toxicity was neutropenia in 3 pts (16.7%).
Conclusions: L is a well-tolerated and active treatment option for patients with SC/NEPC. Prospective studies are needed to determine the role of L in the treatment of SC/NEPC.
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Small cell advanced prostate cancer spread to liver and lungs.
Neuroendocrine vs small cell
Anyone here diagnosed with secondary cancer after chemo and radiation for prostate cancer? 
16-ish Month Update
