UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castrate-sensitive prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 117-117
Author(s):  
Mary Mahler ◽  
Esmail Mutahar Al-Ezzi ◽  
Noa Shani Shrem ◽  
Eric Winquist ◽  
Christina M. Canil ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Median Time ◽  
Median Number ◽  
Time To Progression ◽  
Chemohormonal Therapy ◽  
Radium 223 ◽  
Psa Response ◽  
Number Of Cycles

117 Background: Since docetaxel has been advanced to the metastatic castrate-sensitive prostate cancer (mCSPC) setting, there is a lack of evidence guiding its re-introduction upon castrate-resistant (CR) progression. We sought to identify clinical characteristics and outcomes of patients subjected to docetaxel rechallenge (DR) following prior docetaxel exposure in the mCSPC realm. Methods: Patients rechallenged with docetaxel following treatment in the mCSPC setting were identified from three academic centres in Ontario, Canada. Retrospective chart reviews were performed to identify clinical, treatment and outcome variables. Results: Of the 45 patients with DR initiated between 06/2015 and 07/2020, the median age was 65, 60% had a Gleason score of ≥8, and 64% had an ECOG of ≤1. 56% had bone only metastasis, 4% lymph node only metastasis, 29% bone and lymph node metastasis, and 11% had visceral metastasis. In the mCSPC setting, 98% of patients received 6 cycles of docetaxel with 13% requiring dose delays. Of 43 informative patients, all had a PSA response to chemohormonal therapy. 91% achieved at least a 50% PSA response (PSA50), of which 40% had a 50-89% PSA reduction and 51% had a ≥90% PSA reduction. 29% of patients obtained a PSA nadir of < 0.2 ng/mL. 16% had CR progression in < 6 months, 56% in 6-12 months, and 28% in > 12 months. DR was initiated after a median of 20.8 months (range 6.0-40.4) following the last dose of docetaxel for mCSPC, and was given as first line treatment for CR disease to 7%, second line to 51%, third line to 40%, and fourth line or beyond to 2% of patients. 69% of patients had received an androgen-receptor axis targeted therapy prior to DR, 18% radium 223, and 7% had received a trial drug. Notably, no patients had received cabazitaxel prior to DR. The median number of cycles of docetaxel received at rechallenge was 5 (range 1-11) with 18% of patients requiring treatment delays. 64% of patients stopped treatment due to progression, 16% due to side effects, 7% at the patient’s request, 7% due to completion of the planned number of cycles, and 6% due to death or other causes. Among 44 informative patients, 23% achieved at least a PSA50, with 18% having a 50-90% PSA reduction, and 5% having a ≥90% PSA reduction. The median time to progression (biochemical, radiographic, or death) was 2.3 months (95%CI 1.7-4.4) and the median overall survival was 11.0 months (95%CI 8.5-14.3). Conclusions: DR following exposure to docetaxel in the mCSPC setting resulted in a PSA50 in only around one quarter of patients. Both the median time to progression and overall survival were found to be short. With future investigations, we hope to identify clinical variables that will help predict which patients might benefit most from DR.

Timing of docetaxel chemotherapy and impact on outcomes in metastatic castrate-resistant prostate cancer (MCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 298-298
Author(s):  
Alastair Thomson ◽  
Adam Pollard ◽  
Frances May Mark
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Single Agent ◽  
Specific Antigen ◽  
Response Rates ◽  
Treated Group ◽  
Patient Choice ◽  
Gleason Grade ◽  
Psa Response ◽  
Number Of Cycles

298 Background: Docetaxel use has led to a significant prolongation in overall survival (OS) in metastatic prostate cancer after castrate resistance, with a more substantial OS gain when used in combination with initial androgen deprivation therapy (ADT). There is however limited information on outcomes in patients who initially do not receive chemotherapy, perhaps through patient choice or impaired performance status, who become suitable for docetaxel, comparing earlier with later docetaxel treatment. Methods: We retrospectively reviewed patients’ electronic clinical and prescribing records diagnosed with MCRPC and treated with docetaxel from 01/01/2006 to 24/11/2016 in a single centre in the UK. Data was reviewed for number of individual treatments received pre and post chemotherapy, including initial ADT, enzalutamide, abiraterone, docetaxel, cabazitaxel, mitoxantrone, radium 223, single agent steroids and diethylstilboestrol. Prostate specific antigen (PSA) response, number of cycles and dosing of docetaxel and OS were also reviewed. Results: 168 consecutive patients with MCRPC receiving docetaxel were reviewed. Median Gleason grade across the three groups was 8. 48 patients (29%) received docetaxel after 1 or 2 previous treatments, 105 (63%) after 3 or 4 previous treatments and 15 (9%) after 5 or 6. PSA response rates were superior in the earlier treated group (61%, p=0.003), compared with 30% and 31% respectively in the later groups. Median number of cycles was 5.5 overall, with a mean weighted dose received of 396mg/m2, 373mg/m2 and 301mg/m2 in the after 1 or 2 treatments, after 3 or 4 treatments and after 5 or 6 treatment groups. Median OS from castrate resistance for the earlier group was 29 months, not significantly less (p=0.1) than the 35 months for an intermediate number of prior treatments and 42 months for the later treated group. Conclusions: In this group of patients in routine clinical practice who do not receive docetaxel with initial ADT, PSA response rates are significantly improved and overall dose received is higher with subsequent earlier use. However, overall survival is not significantly different between the early and later docetaxel treated patients.

Radium-223 in the treatment of metastatic castrate-resistant prostate cancer: A real-world Irish experience.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 228-228
Author(s):  
Niamh Peters ◽  
John Gaffney ◽  
Emma Connolly ◽  
Richard Bambury ◽  
Derek Gerard Power ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Alkaline Phosphatase ◽  
Real World ◽  
Median Number ◽  
Prior Chemotherapy ◽  
Factors Associated ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

228 Background: Radium 223 (Ra-223) has been successfully utilised in the trial setting for the treatment of men with metastatic castrate resistant prostate cancer (mCRPC). To date, no real world outcomes from its use in the Irish population have been described. Methods: From September 2016 to March 2019, data from men referred for Ra-223 treatment at our institution was retrospectively collected. We recorded patient characteristics, treatments received and outcomes. Overall Survival (OS) was analysed using the Kaplan-Meier method. Results: 81 men were referred for Ra 223. Complete data was available for 56 men. Median age was 75. 79%(45/56) had over 6 bone metastases and 21%(12/56) had lymph node involvement. The median number of prior systemic treatments for mCRPC was 2. 84%(47/56) of patients were previously treated with Androgen deprivation therapy (ADT); 48%(27/56) Abiraterone, 36%(20/56) Docetaxel, 45%(25/56) Enzalutamide and 9%(5/56) Cabazitaxel. All patients were receiving bone protection agents; 57%(32/56) Zolendronic acid and 43%(24/56) Denosumab. Median ECOG was 1 at the start of treatment and 2 at completion. The median number of treatments received was 4 with 36%(20/56) completing all 6 treatments. The most common toxicity seen was grade1 fatigue occurring in10% (6/56). 17% (10/56) required a blood transfusion during their treatment course. 53%(30/56) required opioid analgesia prior to Ra 223 treatment. 76% of these men (22/30) described improved pain following Rad-223. At a median follow up of 13 months,41%(23/56) were alive. The median OS for the entire group was 7 months. Factors associated with improved OS included ECOG 0-1,fewer than 6 bone metastases, normal alkaline phosphatase level at start of treatment and no prior chemotherapy use. Median OS for those who had not received prior chemotherapy was significantly better than those who had (9 vs 5 months p=0.04). Conclusions: This real world study demonstrates Ra 223 is a well tolerated palliative treatment amongst Irish men with mCRPC. Good performance status, lower alkaline phosphatase, chemotherapy naivety and a low burden of metastatic disease are factors associated with an improved overall survival.

A phase II study to evaluate the effects of docetaxel plus lycopene in advanced castrate-resistant prostate cancer.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 77-77
Author(s):  
Eric Zhuang ◽  
Edward M. Uchio ◽  
Michael B. Lilly ◽  
John P. Fruehauf
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Median Time ◽  
Response Rate ◽  
Phase Ii Study ◽  
Duration Of Response ◽  
Psa Response ◽  
Castrate Resistant Prostate Cancer ◽  
Psa Progression ◽  
Castrate Resistant

77 Background: Lycopene, the carotenoid responsible for the red colors seen in tomatoes, grapefruit, and other foods, has demonstrated synergism with docetaxel in prostate cancer cell culture and tumor xenograft models. This phase II study investigated the clinical activity and safety profile of docetaxel plus lycopene in advanced castrate resistant prostate cancer. Methods: Eligible patients had histologically confirmed adenocarcinoma of the prostate, two rising pre-study prostate specific antigen (PSA) values ≥ 1 ng/ml, and no prior treatment with any chemotherapy, biological therapy, or investigational drug. All patients initially received docetaxel 75mg/m2 every 21 days in combination with lycopene 30 mg orally once daily. The primary endpoint was PSA response rate, defined as the proportion of subjects achieving a ≥ 50% reduction in PSA at any point after starting therapy. Secondary endpoints included median time to PSA progression, duration of response (DOR), and overall survival (OS). Results: Fourteen patients were screened, and thirteen patients were initiated on protocol therapy. Median age was 77 years (range 55-90). Twelve patients (92%) had bone metastases. Four patients (30%) had bone and visceral metastases. The PSA response rate was 76.9% [95% confidence interval (CI), 46.2-94.9], comprising of ten PSA responses. Two patients had a best response of stable disease, yielding a disease control rate of 92% [95% CI, 57.2-98.2]. Median time to PSA progression was 8 months [95% CI, 3.5-8.7]. Median duration of response was 7.3 months [95% CI, 4.8-13.2]. On 5-year follow-up, median overall survival was 35.1 months [95% CI, 25.7-57.7]. The most frequently reported ( > 15%) non-hematologic adverse events included diarrhea, nausea, vomiting, peripheral neuropathy, weight loss, fatigue, onycholysis, and alopecia. One patient (7%) experienced febrile neutropenia. No patients experienced grade 3 or above anemia. Conclusions: The combination of docetaxel with lycopene led to improved PSA response rate and tolerability in patients with advanced castrate resistant prostate cancer. Docetaxel plus lycopene merits further research in this patient population. Clinical trial information: NCT01882985.

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer

2021 ◽  
pp. 89-94
Author(s):  
Philipp Dahm
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Randomized Trial ◽  
Median Time ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Chemohormonal Therapy ◽  
Androgen Ablation ◽  
Hormone Sensitive

This chapter summarizes the findings of the landmark Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) trial conducted in men with metastatic, hormone-sensitive prostate cancer comparing docetaxel therapy plus systemic androgen-deprivation therapy to androgen-deprivation therapy alone. It demonstrated improved median overall survival and median time to progression in the chemotherapy arm at the price of some increased severe adverse events.

Abiraterone acetate in patients with metastatic castration-resistant prostate cancer, chemo-naive, who received a prior diethylstilbestrol therapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 130-130
Author(s):  
Diogo Assed Bastos ◽  
Giovani Thomaz Pioner ◽  
Renato Panhoca ◽  
Marjo Deninson Cardenuto Perez ◽  
Ronaldo Damião ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Median Time ◽  
Abiraterone Acetate ◽  
Serum Testosterone Level ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression ◽  
Serum Androgens

130 Background: The use of diethylstilbestrol (DES) for the treatment of metastatic castration resistant prostate cancer (mCRPC) is very common in developing countries. Retrospective data suggests that abiraterone acetate (AA) is active in patients that progressed to DES. This phase II study evaluated the efficacy and safety of abiraterone acetate in chemotherapy-naïve patients with metastatic CRPC who have progressed to DES. Methods: Patients with DES−refractory metastatic CRPC with ongoing ADT, serum testosterone level < 50 ng/dL and ECOG of 0-2 were included. All patients received AA 1,000 mg with prednisone 5 mg once daily in a 28 days cycles. The primary endpoint was the time to PSA progression (PSAP) by PCWG2 and was previously reported. We present here secondary endpoints: overall survival, PSA response, maximum PSA change from baseline and safety. Results: A total of 46 patients were enrolled, median age was 69.8 years, 76% had gleason > = 7 at diagnosis, median time from metastatic disease to DES discontinuation was 25.9 months, and a median duration of prior DES of 7.2 months. AA treatment resulted in median time to PSA progression of 7.3 months. PSA response rate (³ 50%) was 47.5% (95% CI: 36,1% to 68,5%) at 12 weeks and 57.5% (95% CI: 27.0% to 59.1%) at any time. 93.4% received chemotherapy after progression to AA. The median overall survival was 29.6 months. Substantial declines in serum androgens from baseline to week 12 occurred and in this group a higher proportion of PSA responses occurred. The incidence of adverse events (AEs) related to AA was 74% and prednisone 59%. Hypertension (21.7%), fatigue (19.6%) and oedema peripheral (13.0%) were the most frequent AA related AEs. The most frequent prednisone related AEs were hyperglycaemia (15.2%) hypertension (10.9%). Serious AEs occurred in 23.9% of subjects and 3 subjects (6.5%) died of AEs not related to study drugs. Conclusions: AA is well tolerated and demonstrated activity in mCRPC patients previously treated with DES, therefore it should be considered an option in chemo-naïve patients. Serum androgens levels tend to decrease with AA treatment and are associated with PSA responses. Clinical trial information: NCT02217566.

Predicting benefit of radium 223 based on biochemical response and site of metastasis: A real life multicenter UK study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17034-e17034
Author(s):  
Prantik Das ◽  
Jessica Davies ◽  
Anand Sharma ◽  
Ajith Nair ◽  
Salil Vengalil ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Symptom Control ◽  
Real Life ◽  
Lymph Node Involvement ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Node Involvement ◽  
Psa Response ◽  
Symptomatic Benefit

e17034 Background: Studies have shown an improvement in overall survival (OS) and symptom control in metastatic castration-resistant prostate cancer (mCRPC) with Radium-223 treatment. However, there is little information about predicting outcomes using either PSA or Alkaline Phosphatase (ALP) response or comparing bone only disease to bone and lymph node (LN) involvement. Methods: 335 patients receiving Radium 223 at 6 UK centres between March 2014 and June 2020 were included. The primary endpoint was overall survival, secondary endpoints were toxicity, symptomatic benefit and skeletal-related events(SRE) Results: The median age was 75, with 71% having bone only metastases and 29% also having lymph node involvement. Those with PSA response (30%) had a statistically significant improvement in OS, compared to non-responders (18.2 vs 13.8 months, p = 0.026). They also showed highest rate of imaging response/stable disease (54% vs 34%). ALP response was seen in 82%. This did not translate to significantly improved OS, but did correlate with better symptomatic benefit (40% vs 29%). Those with bone only disease showed a survival benefit compared to those with LN involvement (19.4 vs 11.4 months, p = 0.046). Other than anaemia (23.5%), Grade 2 or above toxicities were uncommon including thrombocytopenia and neutropenia(5.5 and 6.2% respectively ) . 14% patients required at-least one blood transfusion. SRE were seen in 24% overall, but lower of in PSA responders(18%). Conclusions: Real life multicentre data suggests that PSA response and bone only disease could be predictors for better survival following Radium-223, whereas ALP response correlates better with symptomatic benefit.

Sign in / Sign up

Export Citation Format

Share Document