Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Noriyoshi Miura ◽  
Nozomu Tanji ◽  
Yutaka Yanagihara ◽  
Terutaka Noda ◽  
Seiji Asai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Gastric Bleeding ◽  
Castration Resistant ◽  
Analgesic Agents ◽  
Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer

2017 ◽  
Vol 35 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Tomasz M. Beer ◽  
Eugene D. Kwon ◽  
Charles G. Drake ◽  
Karim Fizazi ◽  
Christopher Logothetis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

Purpose Ipilimumab increases antitumor T-cell responses by binding to cytotoxic T-lymphocyte antigen 4. We evaluated treatment with ipilimumab in asymptomatic or minimally symptomatic patients with chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Patients and Methods In this multicenter, double-blind, phase III trial, patients were randomly assigned (2:1) to ipilimumab 10 mg/kg or placebo every 3 weeks for up to four doses. Ipilimumab 10 mg/kg or placebo maintenance therapy was administered to nonprogressing patients every 3 months. The primary end point was overall survival (OS). Results Four hundred patients were randomly assigned to ipilimumab and 202 to placebo; 399 were treated with ipilimumab and 199 with placebo. Median OS was 28.7 months (95% CI, 24.5 to 32.5 months) in the ipilimumab arm versus 29.7 months (95% CI, 26.1 to 34.2 months) in the placebo arm (hazard ratio, 1.11; 95.87% CI, 0.88 to 1.39; P = .3667). Median progression-free survival was 5.6 months in the ipilimumab arm versus 3.8 with placebo arm (hazard ratio, 0.67; 95.87% CI, 0.55 to 0.81). Exploratory analyses showed a higher prostate-specific antigen response rate with ipilimumab (23%) than with placebo (8%). Diarrhea (15%) was the only grade 3 to 4 treatment-related adverse event (AE) reported in ≥ 10% of ipilimumab-treated patients. Nine (2%) deaths occurred in the ipilimumab arm due to treatment-related AEs; no deaths occurred in the placebo arm. Immune-related grade 3 to 4 AEs occurred in 31% and 2% of patients, respectively. Conclusion Ipilimumab did not improve OS in patients with metastatic castration-resistant prostate cancer. The observed increases in progression-free survival and prostate-specific antigen response rates suggest antitumor activity in a patient subset.

Phase II Trial of Consolidation Docetaxel and Samarium-153 in Patients With Bone Metastases From Castration-Resistant Prostate Cancer

2009 ◽  
Vol 27 (15) ◽  
pp. 2429-2435 ◽  
Author(s):  
Karim Fizazi ◽  
Philippe Beuzeboc ◽  
Jean Lumbroso ◽  
Vincent Haddad ◽  
Christophe Massard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Survival Rate ◽  
Bone Metastases ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Psa Relapse ◽  
Castration Resistant ◽  
Psa Response ◽  
Grade 3

PurposeTo assess docetaxel combined with samarium-153–ethylene diamine tetramethylene phosphonic acid (EDTMP), a radiopharmaceutical with a high affinity for bone, in patients with castration-resistant prostate cancer (CRPC).Patients and MethodsPatients with bone metastases from CRPC who achieved a response or stabilization after four cycles of docetaxel and estramustine were given consolidation docetaxel 20 mg/m2/wk for 6 weeks and samarium-153-EDTMP (37 MBq/kg) during week 1. Prostate-specific antigen (PSA) response was assessed by using consensus criteria, and pain was assessed by using a visual analog scale (VAS). This study used a Simon two-step design with PSA–progression-free survival (PFS) as the primary end point.ResultsForty-three patients were included in the trial. A PSA response was obtained in 77% (95% CI, 61% to 82%). The pain response rate was 69% (95% CI, 49% to 85%). At least five of the six planned weekly injections of docetaxel were administered to 34 patients (81%). The consolidation docetaxel–samarium-153–EDTMP regimen was well tolerated; there was no febrile neutropenia, and only two episodes (5%) of rapidly reversible grade 3 thrombocytopenia occurred. Although a serum PSA relapse eventually occurred in all patient cases, this regimen resulted in pain control in the long-term. The median PSA-PFS was 6.4 months (95% CI, 6 to 7 months). The median survival was 29 months (95% CI, 22 to 31); the 1-year survival rate was 77% (62% to 87%); and the 2-year survival rate was 56% (41% to 70%).ConclusionCombining docetaxel and samarium-153–EDTMP in patients with bone metastases from CRPC is well tolerated, and it yields major pain relief that persists long after treatment. Overall survival compares favorably with that expected in this population of patients, most of whom exhibit symptoms.

Efficacy and safety of docetaxel-based chemotherapy in Japanese men over 80 years old with castration-resistant prostate cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16094-e16094 ◽  
Author(s):  
Takeo Kosaka ◽  
Yota Yasumizu ◽  
Ryuichi Mizuno ◽  
Akira Miyajima ◽  
Eiji Kikuchi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Performance Status ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Adverse Event Rate ◽  
Castration Resistant Prostate Cancer ◽  
Japanese Men ◽  
Castration Resistant ◽  
Elderly Japanese ◽  
Grade 3

e16094 Background: Docetaxel-based chemotherapy is widely used to treat castration-resistant prostate cancer (CRPC). However, its efficacy in elderly males has not yet been fully elucidated. In Japan, the number of elderly CRPC patients continues to increase. Therefore, it is urgently necessary to evaluate the effect of docetaxel-based chemotherapy in elderly Japanese men with CRPC. Methods: Sixty-eight male patients with CRPC who were treated with first-line docetaxel-based chemotherapy in a single institution from 2006 to 2011 were evaluated retrospectively. Results: The median age was 72.4 ± 6.5 years. Ten patients (14.7 %) were ≥ 80 years old (older group), and 58 (85.3 %) were < 80 years old (younger group). All patients received docetaxel at a dose of 75 mg/m2 once every 3 weeks, and prednisolone 10 mg was given every day orally. The prostate-specific antigen (PSA) levels of the older and younger groups before docetaxel-based chemotherapy were 41.2 ± 37.4 ng/ml and 106.5 ± 184.7 ng/ml, respectively (P = 0.273). The PSA doubling times before docetaxel-based chemotherapy were 91.6 ± 92.6 days and 92.5 ± 91.9 days, respectively (P = 0.977). The performance status of the older group was 0 or 1. In the same group, 7 patients (70.0%) achieved a PSA decline of ≥ 30% and 4 patients (40.0%) achieved a PSA decline of ≥ 50%. In the younger group, the PSA decline was ≥ 30% in 37 patients (63.8%) and ≥ 50% in 26 patients (44.8%). The PSA decline rates of ≥ 30% and ≥ 50% were not significantly different between the two groups (p = 0.68 and p = 0.75, respectively). Progression-free survival (PFS) was also not significantly different between the two groups (PFS 5.3 vs. 7.3 months, p = 0.39). The major grade 3–4 toxicities were myelosuppression. Grade 3/4 neutropenia occurred in 80.0% of the older group and 78.0% of the younger group, and Grade 4 neutropenia occurred in 20.0% of the older group and 24.2% of the younger group. There were no significant differences between the two groups (Grade 3/4; p = 0.89, Grade 4; p = 0.79). Conclusions: Docetaxel-based chemotherapy showed a significant effect with a tolerable adverse event rate in elderly Japanese males over 80 years old with castration-resistant prostate cancer.

Clinical experience with 100 consecutive patients treated with Lu-177-labeled PSMA-I&T radioligand therapy for metastatic castration-resistant prostate cancer.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 206-206 ◽  
Author(s):  
Matthias Michael Heck ◽  
Sebastian Schwaiger ◽  
Karina Knorr ◽  
Margitta Retz ◽  
Tobias Maurer ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Experience ◽  
Specific Antigen ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Grade 3

206 Background: To report our clinical experience with 177Lutetium-labeled prostate-specific membrane antigen-ligand (177Lu-PSMA-I&T) for systemic radioligand therapy in 100 consecutive patients with metastatic castration-resistant prostate cancer (mCRPC). Methods: All patients were treated under a review board-approved compassionate use protocol. Eligibility criteria for 177Lu-PSMA-I&T therapy included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or unsuitability for taxanes as well as positive 68Ga-PSMA tracer uptake of metastases in a prior PET-scan. Intravenous treatment with 177Lu-PSMA-I&T was given 6- to 8-weekly with an activity of 7.4GBq up to 6 cycles in patients without clinical or radiographic progression. We report prostate-specific antigen (PSA) decline, PSA progression-free survival (PSA-PFS), clinical progression-free survival (cPFS) and overall survival (OS) as well as toxicity. Results: Median age was 72 years (range 46-85) and median PSA level was 164 ng/ml (range 0-6178). Bone, lymph node and visceral metastases were present in 94%, 85% and 33% of patients, respectively. The median number of previous treatment regimens for mCRPC was 3 (range 1-6) and 84% of patients were pretreated with chemotherapy. At the time of evaluation, 286 cycles with 177Lu-PSMA-I&T were applied (median 2 cycles per patient, range 1-6), while treatment was still ongoing in 27% of patients. Overall, 4 and 6 cycles were applied in 33 and 15 patients, respectively. PSA decline ≥30%, ≥50% and ≥90% was achieved in 40%, 32% and 9% of patients, respectively. Median PSA-PFS was 3.4 months (95%CI 2.7-4.0), median cPFS was 4.1 months (95%CI 2.5-5.7) and median OS was 12.2 months (95%CI 8.8-15.7). Treatment-emergent hematologic grade 3/4 toxicities were anemia in 7%, thrombocytopenia in 5% and neutropenia in 4% of patients. Grade 3/4-non-hematologic toxicities were not observed. The main non-hematologic grade 1/2 toxicities were dry mouth in 18%, fatigue in 16% and loss of appetite in 9/% of patients. Conclusions: Radioligand therapy with 177Lu-PSMA I&T appears to be safe and active in late-stage mCRPC.

scholarly journals Combined CTLA-4 and PD-L1 blockade in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer is associated with increased myeloid and neutrophil immune subsets in the bone microenvironment

2021 ◽  
Vol 9 (10) ◽  
pp. e002919
Author(s):  
Sumit K Subudhi ◽  
Bilal A Siddiqui ◽  
Ana M Aparicio ◽  
Shalini S Yadav ◽  
Sreyashi Basu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Immune Checkpoints ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Castration Resistant ◽  
Number Of Patients ◽  
Measurable Disease

BackgroundImmune checkpoint therapy (ICT) has low response rates in patients with metastatic castration-resistant prostate cancer (mCRPC), in part due to few T cells in the tumor microenvironment (TME). Anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) promotes intratumoral T cell infiltration but induces upregulation of PD-1 and programmed death ligand-1 (PD-L1) within the prostate TME. Combined anti-CTLA-4 plus anti-PD-1 can partly overcome this adaptive resistance and was recently shown to augment responses in patients with mCRPC with measurable disease. Although bone is the most common site of metastasis in prostate cancer, patients with bone-predominant disease are frequently excluded from trials because they lack measurable disease, which limits assessment of disease progression and tissue sampling. We therefore designed this study to investigate combined ICT in mCRPC to bone.HypothesisCombined anti-CTLA-4 (tremelimumab) plus anti-PD-L1 (durvalumab) is safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone.Patients and methodsIn this single-arm pilot study, men with chemotherapy-naïve mCRPC to bone received tremelimumab (75 mg intravenous) plus durvalumab (1500 mg intravenous) every 4 weeks (up to four doses), followed by durvalumab (1500 mg intravenous) maintenance every 4 weeks (up to nine doses). The primary endpoint was incidence of adverse events. Secondary endpoints included serum prostate-specific antigen (PSA), progression-free survival (PFS), radiographic PFS (rPFS), and maximal PSA decline.ResultsTwenty-six patients were treated between August 8, 2017 and March 28, 2019. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 11 patients (42%), with no grade 4 or 5 events. TRAEs leading to discontinuation occurred in three patients (12%). PSA decline ≥50% occurred in three patients (12%). Six patients (24%) achieved stable disease for >6 months. At a median follow-up of 43.6 months, median rPFS was 3.7 months (95% CI: 1.9 to 5.7), and median overall survival was 28.1 months (95% CI: 14.5 to 37.3). Post-treatment evaluation of the bone microenvironment revealed transcriptional upregulation in myeloid and neutrophil immune subset signatures and increased expression of inhibitory immune checkpoints.ConclusionsTremelimumab plus durvalumab was safe and well tolerated in patients with chemotherapy-naïve mCRPC to bone, with potential activity in a small number of patients as measured by rPFS. Combination of CTLA-4 and PD-L1 blockade with therapies targeting the myeloid compartment or other inhibitory immune receptors may be necessary to overcome mechanisms of resistance within prostate bone microenvironment.Trial registration numberNCT03204812.

scholarly journals Safety and Efficacy of First-Line Treatments for Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Indirect Comparison

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Haofeng Zheng ◽  
Jialiang Chen ◽  
Wenhan Qiu ◽  
Sijie Lin ◽  
Yanxiong Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Specific Antigen ◽  
Indirect Comparison ◽  
Progression Free Survival ◽  
Optimal Order ◽  
Castration Resistant Prostate Cancer ◽  
First Line ◽  
Safety And Efficacy ◽  
Castration Resistant

Recently, several drugs have been introduced for the first-line treatment of chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC), but few studies have compared treatment outcomes directly. This indirect comparison among 10 clinical trials (n= 4870 patients) retrieved from PubMed, Web of Science, Cochrane Collaboration, and ClinicalTrails.gov was performed to assess the safety and efficacy of docetaxel, cabazitaxel, abiraterone, enzalutamide, and sipuleucel-T for the initial treatment of mCRPC. No significant differences in primary outcome (overall survival) were found among initial treatments. However, docetaxel had the highest probability (37.53%) of being the most effective, but at the cost of more adverse events, while enzalutamide was associated with the best secondary outcomes (prostate-specific antigen response, progression-free survival, quality of life, and adverse event profile). Thus, docetaxel is recommended as the first agent used for the chemotherapy of mCRPC, while enzalutamide is recommended as the first nonchemotherapy treatment. Additional clinical trials are needed to confirm these findings and establish the optimal order for multidrug treatment of mCRPC.

Peptide vaccines with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive castration resistant prostate cancer: A randomized phase II study.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 3-3
Author(s):  
Hirotsugu Uemura ◽  
Takahiro Kimura ◽  
Takafumi Minami ◽  
Kazuhiro Yoshimura ◽  
Masahiro Nozawa ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Early Stage ◽  
Phase 1 ◽  
Peptide Vaccine ◽  
Progression Free Survival ◽  
Peptide Vaccines ◽  
Castration Resistant Prostate Cancer ◽  
Peptide Vaccination ◽  
Castration Resistant

3 Background: We previously developed MHC class I restricted peptide vaccines for prostate cancer and carried out a phase 1 trial for castration resistant prostate cancer (CRPC) patients to assess safety and immunological evaluation. In the present study, we conducted a randomized phase 2 trial to evaluate the efficacy of peptide vaccination therapy for chemotherapy-naive CRPC patients. Methods: Early-stage CRPC (PSA<10ng/ml) patients positive for HLA-A02 or A24 or A3 super family were randomized into two treatment groups; peptide vaccine with low dose (1mg/day) dexamethasone (Dx) versus low dose Dx alone. Patients were vaccinated subcutaneously with 3 mg of selected peptides (max. 4 kinds) 6 times at two weeks interval. Dx 1mg/day p.o. was started on the first day of peptide vaccination. Toxicity was assessed monthly, and immunological responses such as cytotoxic T lymphocyte activity and clinical responses were evaluated every 3 months. The primary endpoint of this study is progression-free survival including serum PSA. Secondary endpoints are overall survival and safety. Results: A total of 83 chemotherapy-naive CRPC patients were selected for this trial. Of these 10 patients were excluded due to HLA type mismatch and exclusion criteria. 73 patients were enrolled and randomized; 37 in the vaccine treatment group and 36 in the Dx group. One patient in the Dx group self-withdrew from the study immediate after the randomization. Median time to PSA failure in the vaccine group was significant longer than the Dx group; 602 days vs 210 days, p<0.001 (Table). Conclusions: These findings suggest that combination therapy of peptide vaccines and low dose dexamethasone may be a promising tool for chemotherapy-naive CRPC patients. Clinical trial information: UMIN000000959.[Table: see text]

ARCHES: Efficacy of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5048-5048
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Jeffrey M. Holzbeierlein ◽  
Arnauld Villers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiographic Progression ◽  
Progression Free Survival ◽  
High Volume ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Prior Therapy ◽  
Castration Resistant ◽  
Secondary Endpoints ◽  
Grade 3

5048 Background: ENZA has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). ARCHES assessed the efficacy of ENZA with ADT in men with mHSPC, including pre-specified subgroups based on prior therapy. Methods: ARCHES, a multinational, double-blind, Phase 3 study (NCT02677896), randomized patients (pts) with mHSPC 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel (doce) use. Primary endpoint was radiographic progression-free survival (rPFS; centrally assessed radiographic progression or death within 24 weeks of treatment discontinuation). Secondary endpoints included time to initiation of new antineoplastic therapy and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n = 574) or PBO (n = 576). Overall, 63% had high-volume disease, 18% had prior doce, and 91% had prior ADT or orchiectomy (orch). Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); significant improvements in rPFS were also reported in prior treatment subgroups. Secondary endpoints improved with ENZA + ADT (Table), with no significant impact in time to deterioration in urinary symptoms. OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs. 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs. PBO + ADT in men with mHSPC. Preliminary safety analysis appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Clinical trial information: NCT02677896. [Table: see text]

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