Contemporary experience with ketoconazole in patients with metastatic castration-resistant prostate cancer: Clinical factors associated with PSA response and disease progression

e16548 Background: There is scarce information on the efficacy of low-dose enzalutamide in metastatic castration-resistant prostate cancer. We report on a series treated with half dose enzalutamide. Methods: We observed a trend in our practice to initiate low-dose enzalutamide at the time of disease progression in older patients considered frail, presenting with cardio-vascular comorbidity or with history of neurological symptoms. Records were retrospectively reviewed. The selection criteria were: 1) Metastatic disease demonstrated by at least one imaging modality, CT, bone scan, or positron emission tomography. 2) Progression of prostate specific antigen (PSA). 3) Castrate testosterone level ( < 0.2 ng/mL). 4) Enzalutamide treatment at 80 mg or less, once daily. To estimate the rate of PSA response, we used linear interpolation to compute the time from the initiation of low-dose enzalutamide to 50% PSA reduction. Results: Between November 2015 and December 2018 at the Martinique University Hospital, 10 patients matching the selection criteria were treated with ≤ 80 mg enzalutamide od: 8 started de novo with the low dose, 2 started with 160 mg but required dose reduction for intolerance. The mean age was 78 years (range 67-84). Three had painful bone metastases. The mean PSA at start of low dose enzalutamide was 88 ng/mL (range 1.06 - 251.8). All patients were maintained with reduced dose. At the current follow-up of 9 months (range 0 - 36 months), PSA response was observed in 7 patients ( = 70%), 1 was not evaluable (PSA not assessed), 2 did not respond. Of the 2 non-responders, one had no sign or symptom of disease progression; the other presented with extensive disease progression previously treated with abiraterone, he refused to receive increased dose enzalutamide. Among the 7 responders, the time to 50% PSA reduction was 57 days (range 26 - 119). Currently, the decline of PSA remains sustained in 6 of the 7 responders, it increased in 1 who discontinued enzalutamide. Pain decreased in the 3 symptomatic patients, including the PSA non-responder. Conclusions: Low dose enzalutamide appears efficient in a large proportion of selected frail patients. Further follow-up is required to evaluate the long-term response.

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222: Radium-223 in Metastatic Castration-Resistant Prostate Cancer: Single-Institution Analysis of Factors Associated with Treatment Completion and Survival

Radiotherapy and Oncology ◽

10.1016/s0167-8140(16)33621-0 ◽

2016 ◽

Vol 120 ◽

pp. S81

Author(s):

Andrew Bang ◽

Shawn Malone ◽

Eugene Leung ◽

Christina Canil ◽

Libni Eapen ◽

...

Keyword(s):

Prostate Cancer ◽

Treatment Completion ◽

Castration Resistant Prostate Cancer ◽

Single Institution ◽

Factors Associated ◽

Castration Resistant ◽

Radium 223

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PSMA Expression Predicts Early Biochemical Response in Patients with Metastatic Castration-Resistant Prostate Cancer under 177Lu-PSMA-617 Radioligand Therapy

Cancers ◽

10.3390/cancers13122938 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2938

Author(s):

Liam Widjaja ◽

Rudolf A. Werner ◽

Tobias L. Ross ◽

Frank M. Bengel ◽

Thorsten Derlin

Keyword(s):

Prostate Cancer ◽

Whole Body ◽

Biochemical Response ◽

Clinical Parameters ◽

Castration Resistant Prostate Cancer ◽

Radioligand Therapy ◽

Castration Resistant ◽

Psa Response ◽

High Age ◽

Psma Expression

177Lu-Prostate-specific membrane antigen (PSMA)-radioligand therapy (RLT) is a promising treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to determine the predictive value of pretherapeutic PSMA-ligand positron emission tomography (PET) and established clinical parameters for early biochemical response after two cycles of RLT. In total, 71 mCRPC patients who had undergone PET/computed tomography (CT) with 68Ga-PSMA-11 prior to two cycles of 177Lu-PSMA-617 RLT were included. Malignant lesions on pretherapeutic PET/CTs were manually segmented and average maximum PSMA expression (maximum standardized uptake values, SUVmax), whole-body PSMA-tumor volume (TV), and whole-body total lesion (TL)-PSMA were calculated. We then tested the predictive performance of these parameters for early biochemical response (defined as prostate-sepcific antigen (PSA) decrease of ≥50% according to PCWG2) after two cycles of RLT, relative to established clinical parameters. Early PSA response was observed in 34/71 patients. PSA change after two cycles of RLT correlated with pretherapeutic SUVmax (r = −0.49; p < 0.001), but not with PSMA-TV (r = 0.02; p = 0.89) or TL-PSMA (r = −0.15; p = 0.22). A cut-off of 19.8 for SUVmax and 75.5 years for age was defined by receiver operating characteristics and revealed a significant outcome difference for early biochemical response between patients with adversely low vs. high PSMA expression and low vs. high age (p < 0.001). Multivariate analysis identified SUVmax (HR, 7.94, p = 0.001) and age (HR, 8.05, p = 0.002) as independent predictors for PSA response early in the treatment course. Thus, high age and high PSMA expression in patients scheduled for RLT identify patients with early biochemical response. This study provides a rationale for further prospective studies exploring PET-guided treatment intensification in selected patients.

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MP50-20 IMPACT OF ABIRATERONE ACETATE IN PROSTATE SPECIFIC ANTIGEN TRIAL UPDATE: EFFECT OF ABIRATERONE ACETATE AND LOW DOSE PREDNISONE ON PROSTATE-SPECIFIC ANTIGEN AND RADIOGRAPHIC DISEASE PROGRESSION IN PATIENTS WITH NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER

The Journal of Urology ◽

10.1016/j.juro.2016.02.454 ◽

2016 ◽

Vol 195 (4S) ◽

Author(s):

Charles Ryan ◽

E. David Crawford ◽

Neal D Shore ◽

Willie Underwood ◽

Anil Londhe ◽

...

Keyword(s):

Prostate Cancer ◽

Disease Progression ◽

Prostate Specific Antigen ◽

Low Dose ◽

Specific Antigen ◽

Abiraterone Acetate ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Radiographic Disease ◽

Dose Prednisone

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Abiraterone in patients with metastatic castration-resistant prostate cancer progressing after docetaxel and MDV3100.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4554 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4554-4554 ◽

Cited By ~ 6

Author(s):

Ecaterina Ileana ◽

Yohann Loriot ◽

Laurence Albiges ◽

Christophe Massard ◽

Aurore Blesius ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Progression ◽

Specific Antigen ◽

Patient Characteristics ◽

Preliminary Evidence ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Symptom Response ◽

Psa Response ◽

Metastatic Sites

4554 Background: Chemotherapy with docetaxel is the standard first-line treatment in patients with metastatic castration-resistant prostate cancer (mCRPC). In patients progressing after docetaxel, both abiraterone and MDV3100 have yielded improved survival for patients with mCRPC. The efficacy of abiraterone in patients pre-treated with MDV 3100 is unknown. Methods: We investigated abiraterone-prednisone in 24 patients with cancer progression after docetaxel followed by MDV3100. All patients received abiraterone 1000 mg/day plus prednisone 10mg/day. Prostate-specific antigen (PSA) response, symptom response, and time to progression were assessed. Results: Patient characteristics were as follows: median age: 74 years (53-84), median PSA: 108 ng/mL (2-2541), metastatic sites: bone: all 24 patients, liver/lung: 6 patients (25%), and lymph nodes : 9 patients (38%). Five patients (21%) had a PSA decrease on abiraterone-prednisone. Three patients (13%) achieved a PSA response, defined as a decrease of >50% in PSA, confirmed after≥ 4 weeks. The duration of PSA response was 2, 3 and 4.5 months. Six patients (29%) had a symptomatic response on the pain score and analgesic consumption was decreased. Treatment was well tolerated. Abiraterone-prednisone was discontinued in one patient due to edema and hypokaliemia. Conclusions: This study shows preliminary evidence that abiraterone-prednisone yields activity in patients with mCRPC pretreated with docetaxel and MDV3100.

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Activity of gemcitabine-oxalipaltin (GemOx) plus prednisolone in patients with castration-resistant prostate cancer (CRPC) for whom docetaxel-based chemotherapy failed.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.108 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 108-108

Author(s):

Jae-Lyun Lee ◽

Yesul Kim ◽

Jin-Hee Ahn ◽

MeeKyung Choi ◽

Seung-Woo Hong ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Synergistic Effects ◽

Drug Effects ◽

Fixed Dose ◽

Castration Resistant Prostate Cancer ◽

Castration Resistant ◽

Psa Response ◽

Psa Progression ◽

Grade 3

108 Background: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of GemOx in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity in LNCaP, PC3 and DU145 cell lines. The combined drug effects were evaluated using the Chou and Taladay analysis. Clinically, patients with CRPC who failed prior docetaxel chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2/min) and oxaliplatin 100 mg/m2 intravenously every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerability develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate (PCWG 1.0 criteria). Results: The IC50of gemcitabine and oxaliplatin were, respectively, 1.25 μM and 0.69 μM for LNCaP cells; 50.00+ μM and 12.81 μM for PC3 cells; and 11.23 μM and 11.04 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 31 patients were accrued. At the time of this analysis 7 patients were still continuing treatment. The median age was 67 years (range 57 ~ 81) and the median dose of docetaxel exposure was 525 mg/m2. A total of 231 cycles administered with a median of 9 cycles per patient. PSA responses were observed in 52% (95% CI, 34~69) and partial responses were observed in 7 of 10 patients with measurable disease. Out of 23 patients, 10 patients achieved pain response (44%). With a median FU duration of 8.0 months, the median time to PSA progression was 6.4 months (95% CI, 3.5~9.2). Peripheral neuropathy developed in 78% of patients but remained of grade 1 ~2 intensities. Frequently observed grade 3 or 4 toxicities were neutropenia (10%), thrombocytopenia (10%), anemia (3%), and diarrhea (3%). Conclusions: GemOx is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720). Clinical trial information: NCT01487720.

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Dose-modified abiraterone acetate (AA) in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Centre (PM) experience.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.61 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 61-61 ◽

Cited By ~ 1

Author(s):

Raya Leibowitz-Amit ◽

Eshetu G. Atenafu ◽

Jo-An Seah ◽

Arnoud J. Templeton ◽

Francisco Emilio Vera-Badillo ◽

...

Keyword(s):

Prostate Cancer ◽

Phase I ◽

Low Dose ◽

Abiraterone Acetate ◽

Low Doses ◽

Fasting State ◽

Castration Resistant Prostate Cancer ◽

High Fat ◽

Castration Resistant ◽

Psa Response

61 Background: AA prolongs survival in mCRPC and is used pre- and post-chemotherapy. In the phase I trial, AA showed anti-tumor activity at 250 or 500 mg daily (‘low doses’). In addition, pharmacokinetic analysis showed that when AA was administered with a high-fat meal vs the fasting state, drug exposure was increased by 4.4-fold [ Attard G et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563-4571.]. Based on this, at our cancer centre low-dose AA is sometimes prescribed with high-fat meals to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Our aim was to study the association between AA dose, PSA response and progression-free survival (PFS). Methods: All men receiving AA at PM (Nov2009-Mar2013) were reviewed retrospectively. PSA response rate (PSA-RR) was defined according to PCWG2 criteria as a confirmed decrease ≥50% in PSA. PFS was defined from start of AA to PSA progression, clinical progression, drug cessation or death. Associations between dose, PSA-RR and PFS were assessed using chi-square and logrank tests, respectively, for all patients and for the sub-group of chemo-naive patients. Results: 109 men were treated with AA, 89 at a full dose of 1000 mg in the fasting state, 20 at low doses with high-fat meals. There was no significant difference in PFS between the two dose levels for all men. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full dose (p=0.09; table). Conclusions: Administration of low dose AA with high-fat meals is not associated with shorter PFS despite a trend to lower PSA-RR. These results are clinically relevant in resource-limited settings and warrant further prospective clinical research. [Table: see text]

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The effect of prior abiraterone (Abi) use on the activity of enzalutamide (Enza) in men with mCRPC.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.18 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 18-18 ◽

Cited By ~ 20

Author(s):

Heather H. Cheng ◽

Rosa Nadal ◽

Roman Gulati ◽

Arun Azad ◽

Przemyslaw Twardowski ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Subsequent Treatment ◽

Significant Response ◽

Castration Resistant Prostate Cancer ◽

Steroid Use ◽

Castration Resistant ◽

Disease Characteristics ◽

Psa Response ◽

Time Of Presentation

18 Background: Enzalutamide (Enza) and abiraterone (Abi) are next generation hormonal agents for metastatic castration resistant prostate cancer (mCRPC). Whether these agents can be effectively sequenced is not yet well understood. Results of retrospective analyses of Abi after prior Enza have demonstrated modest responses of brief duration, suggesting common resistance pathways. Here, we retrospectively analyze response to Enza with or without prior Abi treatment. Methods: We retrospectively reviewed 195 patients from seven academic centers treated with Enza between January 2009 and August 2013. Data were collected on disease characteristics, prior therapies, and prostate-specific antigen (PSA) values at baseline and while on treatment. Logistic regression was used to evaluate association between 30% or greater PSA decline on Enza and either prior Abi treatment or 30% or greater PSA decline on prior Abi after accounting for potential confounders. Results: One hudred eighty three patients had non-missing PSA starting and nadir values on Enza, with starting PSA median 102.0 (range 1.1–5007.0) ng/mL. Overall, 42% (76 of 183) of Enza-treated patients achieved a 30% or greater PSA decline, with 39% (58 of 150) response among prior Abi-treated patients and 55% (18 of 33) response among Abi-naïve patients. Of 79 patients who lacked significant response to prior Abi, 30% (25 of 79) achieved a 30% or greater PSA decline and 19% (15 of 79) achieved a 50% or greater PSA decline with subsequent Enza. Odds of achieving a 30% or greater PSA response on Enza was 2.3 times higher for Abi-naïve patients versus prior Abi-treated patients (95% CI 1.0–5.5, P=0.06) and 1.9 times higher for Abi-responders vs Abi-non-responders (95% CI 1.0–3.7, P=0.06) after adjusting for prior docetaxel and concurrent steroid use. Conclusions: In this multi-center retrospective study, 39% of patients achieved a 30% or greater PSA decline with Enza after prior Abi treatment. While the activity of Enza appears to be blunted in the post-Abi setting, PSA declines still occur in a meaningful proportion of patients. Notably, 30% of patients without significant response to prior Abi responded to subsequent treatment with Enza, suggesting a subset of men with distinct biological resistance pathways. Data will be updated at the time of presentation.

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